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https://en.wikipedia.org/wiki/EPH%20receptor%20B4 | Ephrin type-B receptor 4 is a protein that in humans is encoded by the EPHB4 gene.
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development.
References
Further reading
Tyrosine kinase receptors |
https://en.wikipedia.org/wiki/GNAO1 | Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.
Mutations in this gene have been shown to cause epileptic encephalopathy.
Interactions
GNAO1 has been shown to interact with:
RGS5,
RGS19,
RGS20, and
RIC8A
References
Further reading |
https://en.wikipedia.org/wiki/Host%20cell%20factor%20C1 | Host cell factor 1 (HCFC1, HCF1, or HCF-1), also known as VP16-accessory protein, is a protein that in humans is encoded by the HCFC1 gene.
Structure
HCF1 is a member of the highly conserved host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear transcription coregulator is proteolytically cleaved at one or more of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains which interact through electrostatic forces.
Function
HCF1 is involved in control of the cell cycle as well as having regulatory roles in a multitude of processes related to transcription. Additionally, work in model organisms point to HCF1 as being a putative longevity determinant. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.
Mutations in this gene have been linked to disorders of the cobalamine metabolism.
Interactions
Host cell factor C1 has been shown to interact with:
BAP1,
CREB3,
GABPA,
HDAC1,
HDAC2,
MLL,
OGT,
PDCD2,
POU2F1,
PPP1CA,
SIN3A,
SP1,
SUDS3,
WDR5, and
ZBTB17.
References
Further reading
Kelch proteins |
https://en.wikipedia.org/wiki/HLA-DMB | HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.
Function
HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail.
Clinical significance
HLA-DMB is upregulated in tumor tissue of Caucasian but not African patients. Its role in tumor immunology is undefined but has been shown to positively correlated with increased T-cell infiltration and improved prognosis in ovarian cancer. Differential immune processes mediated by HLA-DMB may contribute to the disparity in cancer outcome.
References
Further reading
MHC class II |
https://en.wikipedia.org/wiki/RBPJ | Recombination signal binding protein for immunoglobulin kappa J region is a protein that in humans is encoded by the RBPJ gene.
RBPJ also known as CBF1, is the human homolog for the Drosophila gene Suppressor of Hairless. Its promoter region is classically used to demonstrate Notch1 signaling.
Interactions
RBPJ has been shown to interact with:
NOTCH1
NCOR2,
PCAF,
SND1,
SNW1,
SOX18, and
HIF1a.
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Integrin%20beta%205 | Integrin beta-5 is a protein that in humans is encoded by the ITGB5 gene.
Interactions
Integrin, beta 5 has been shown to interact with PTK2, Annexin A5 and PAK4.
Functions
ITGB5 encodes a subunit of integrin that can interact with several alpha chains to form a variety of integrin heterodimers. It also plays a potential role in intercellular communication during tumor progression and metastasis.
Clinical significance
Research
Elevated levels of ITGB5 have been found in patients with autosomal dominant osteopetrosis type II, a rare disease of bones.
References
Further reading
External links
ITGB5 Info with links in the Cell Migration Gateway
Integrins |
https://en.wikipedia.org/wiki/MDM4 | Protein Mdm4 is a protein that in humans is encoded by the MDM4 gene.
Function
The human MDM4 gene, which plays a role in apoptosis, encodes a 490-amino acid protein containing a RING finger domain and a putative nuclear localization signal. The MDM4 putative nuclear localization signal, which all Mdm proteins contain, is located in the C-terminal region of the protein. The mRNA is expressed at a high level in thymus and at lower levels in all other tissues tested. MDM4 protein produced by in vitro translation interacts with p53 via a binding domain located in the N-terminal region of the MDM4 protein. MDM4 shows significant structural similarity to p53-binding protein MDM2
Interactions
MDM4 has been shown to interact with E2F1, Mdm2 and P53.
References
Further reading |
https://en.wikipedia.org/wiki/Myosin%20binding%20protein%20C%2C%20cardiac | The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. This isoform is expressed exclusively in heart muscle during human and mouse development, and is distinct from those expressed in slow skeletal muscle (MYBPC1) and fast skeletal muscle (MYBPC2).
Structure
cMyBP-C is a 140.5 kDa protein composed of 1273 amino acids. cMyBP-C is a myosin-associated protein that binds at 43 nm intervals along the myosin thick filament backbone, stretching for 200 nm on either side of the M-line within the crossbridge-bearing zone (C-region) of the A band in striated muscle. The approximate stoichiometry of cMyBP-C along the thick filament is 1 per 9-10 myosin molecules, or 37 cMyBP-C molecules per thick filament. In addition to myosin, cMyBP-C also binds titin and actin. The cMyBP-C isoform expressed in cardiac muscle differs from those expressed in slow and fast skeletal muscle (MYBPC1 and MYBPC2, respectively) by three features: (1) an additional immunoglobulin (Ig)-like domain on the N-terminus, (2) a linker region between the second and third Ig domains, and (3) an additional loop in the sixth Ig domain. cMyBP-C appears necessary for normal order, filament length and lattice spacing within the structure of the sarcomere.
Function
cMyBP-C is not essential for sarcomere formation during embryogenesis, but is crucial for sarcomere organization and maintenance of normal cardiac function. Absence of cMyBP-C (Mybpc3-targeted knock-out mice) r |
https://en.wikipedia.org/wiki/Protein%20kinase%2C%20AMP-activated%2C%20alpha%201 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.
The protein encoded by this gene belongs to the serine/threonine protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
Interactions
Protein kinase, AMP-activated, alpha 1 has been shown to interact with TSC2.
References
Further reading
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)
EC 2.7.11 |
https://en.wikipedia.org/wiki/PSMA6 | Proteasome subunit alpha type-6 is a protein that in humans is encoded by the PSMA6 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
Structure
Protein expression
The gene PMSA6 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. A pseudogene has been identified on the Y chromosome. The gene has 8 exons and locates at chromosome band 14q13. The human protein proteasome subunit alpha type-6 is also known as 20S proteasome subunit alpha-1 (based on systematic nomenclature). The protein is 27 kDa in size and composed of 246 amino acids. The calculated theoretical pI (isoelectric point) of this protein is 6.35.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.
Function
Crystal structures of isolated 2 |
https://en.wikipedia.org/wiki/PSME1 | Proteasome activator complex subunit 1 is a protein that in humans is encoded by the PSME1 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the alpha subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three alpha and three beta subunits combine to form a heterohexameric ring. Two transcripts encoding different isoforms have been identified.
Interactions
PSME1 has been shown to interact with:
Emerin and
PSME2.
References
Further reading |
https://en.wikipedia.org/wiki/PTPN13 | Tyrosine-protein phosphatase non-receptor type 13 is an enzyme that in humans is encoded by the PTPN13 gene.
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large protein that possesses a PTP domain at C-terminus, and multiple noncatalytic domains, which include a domain with similarity to band 4.1 superfamily of cytoskeletal-associated proteins, a region consisting of five PDZ domains, and a leucine zipper motif. This PTP was found to interact with, and dephosphorylate Fas receptor, as well as IkappaBalpha through the PDZ domains, which suggested its role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathway. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported.
Interactions
PTPN13 has been shown to interact with PKN2.
References
Further reading |
https://en.wikipedia.org/wiki/Peripherin%202 | Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye. Defects in this protein result in one form of retinitis pigmentosa, an incurable blindness.
Mutations in the PRPH2 gene are associated with Vitelliform macular dystrophy.
Function
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four transmembrane helices. Tetraspanins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility.
Peripherin 2 (sometimes referred to as peripherin/RDS or simply RDS) is a cell surface glycoprotein found in the outer segment of both rod and cone photoreceptor cells. It is located in the rim regions of the flattened disks that contain rhodopsin, which is the protein that is responsible for initiation of visual phototransduction upon reception of light. Peripherin 2 may function as an adhesion molecule involved in stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. This protein is essential for disk morphogenesis.
Clinical significance
Defects in this gene are associated with both central and peripheral retinal degenerations. Some of the various phenotypically different disorders are autosomal dominant retinitis pigmentosa, progr |
https://en.wikipedia.org/wiki/SMARCA2 | Probable global transcription activator SNF2L2 is a protein that in humans is encoded by the SMARCA2 gene.
Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Two transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism.
Interactions
SMARCA2 has been shown to interact with:
ACTL6A,
ARID1B,
CEBPB,
POLR2A,
Prohibitin,
SIN3A,
SMARCB1,
SMARCC1, and
SS18.
- Nicolaides Baraitser Syndrome (NCBRS)
References
Further reading |
https://en.wikipedia.org/wiki/Sphingomyelin%20phosphodiesterase%201 | Sphingomyelin phosphodiesterase 1 (SMPD1), also known as acid sphingomyelinase (ASM), is an enzyme that in humans is encoded by the SMPD1 gene.
Sphingomyelin phosphodiesterase 1 belongs to the sphingomyelin phosphodiesterase family.
Clinical significance
Defects in SMPD1 gene cause Niemann–Pick disease, SMPD1-associated.
A L302P mutation in the SMPD1 gene as a risk factor for Parkinson disease.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Acid Sphingomyelinase Deficiency Includes: Niemann-Pick Disease Type A, Niemann-Pick Disease Type B
OMIM entries on Acid Sphingomyelinase Deficiency |
https://en.wikipedia.org/wiki/T-complex%201 | T-complex protein 1 subunit alpha is a protein that in humans is encoded by the TCP1 gene.
Function
This gene encodes a molecular chaperone that is a member of the TRiC complex. This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized.
Interactions
T-complex 1 has been shown to interact with PPP4C and HDAC3. CCT also directly interacts with lectin type oxidized LDL receptor-1 (LOX-1) while its ligand oxidized low density lipoprotein (OxLDL) disassociates CCT from LOX-1.
Notes
References
Further reading |
https://en.wikipedia.org/wiki/HIST2H2BE | Histone H2B type 2-E is a protein that in humans is encoded by the HIST2H2BE gene.
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a member of the histone H2B family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif.
Cancer
HIST2H2BE gene has been detected progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, this gene is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.
References
Further reading
External links |
https://en.wikipedia.org/wiki/RIPK1 | Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK.
RIPK1 is an enzyme that in humans is encoded by the RIPK1 gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family.
Structure
RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. It contains a serine/threonine kinase domain (KD) in the 300 aa N-Terminus, a death domain (DD) in the 112 aa C-Terminus, and a central region between the KD and DD called intermediate domain (ID).
The kinase domain plays different roles in cell survival and is important in necroptosis induction. RIP interacts with TRAF2 via the kinase domain. The KD can also interact with Necrostatin-1, which is an allosteric inhibitor of RIPK1 kinase activity. Overexpression of RIP lacking kinase activity can activate NF-kB.
The death domain is homologous to the DD of other receptors such as Fas, TRAILR2 (DR5), TNFR1 and TRAILR1 (DR4), so it can bind to these receptors, as well as TRADD and FADD in the TNFR1 signalling complex. Overexpression of RIP can induce apoptosis and can activate NF-kB, but overexpression of the RIP death domain can |
https://en.wikipedia.org/wiki/Ch%C3%A2teau%20Troplong%20Mondot | Château Troplong Mondot is a Bordeaux wine from the appellation Saint-Émilion, ranked Premier grand cru classé B in the Classification of Saint-Émilion wine. The winery is located in the Right Bank of France’s Bordeaux wine region in the commune of Saint-Émilion, adjacent to Château Pavie.
The château also produces a second wine since 1985 named Château Mondot.
History
Originally part of the De Sèze estate in the 18th century, the vineyard situated on the crest of Mondot included what is today Pavie. By the mid-19th century, the Mondot family had acquired a great portion of the land, and in 1936 it came into the ownership of Alexandre Valette. Historically not a widely known winery, it has had success in recent years, considered by many to some extent attributable to the château's collaboration with Michel Rolland.Between 1993 and 1994 the wines at Troplong-Mondot were made by 2012 Food and Wine Magazine Winemaker of the Year Aaron Pott.
Production
The vineyard area extends 33 hectares, with a grape variety of 90% Merlot, 5% Cabernet Sauvignon and 5% Cabernet Franc. The estate averages an annual production of 10,000 of its Grand Vin and 800 cases of its second wine Mondot.
References
External links
Château Troplong Mondot official site
Chateau Troplong Mondot brief story
Bordeaux wine producers |
https://en.wikipedia.org/wiki/Subthreshold%20membrane%20potential%20oscillations | Subthreshold membrane potential oscillations are membrane oscillations that do not directly trigger an action potential since they do not reach the necessary threshold for firing. However, they may facilitate sensory signal processing.
Neurons produce action potentials when their membrane potential increases past a critical threshold. In order for neurons to reach threshold for action potential to fire, enough sodium (Na+) ions must enter the cell through voltage gated sodium channels through membrane and depolarize the cell. The threshold is reached to overcome the electrochemical equilibrium within a neuron, where there is a balance between potassium ions (K+) moving down their concentration gradient (inside the cell to outside), and the electrical gradient that prevents K+ from moving down its own gradient. Once the threshold value is reached, an action potential is produced, causing a rapid increase of Na+ enters the cell with more Na+ channels along the membrane opening, resulting in a rapid depolarization of the cell. Once the cell has been depolarized, voltage-gated sodium channels close, causing potassium channels to open; K+ ions then proceed to move against their concentration gradient out of the cell.
However, if the voltage is below the threshold, the neuron does not fire, but the membrane potential still fluctuates due to postsynaptic potentials and intrinsic electrical properties of neurons. Therefore, these subthreshold membrane potential oscillations do not |
https://en.wikipedia.org/wiki/Bol%C3%ADvar%20Municipality%2C%20T%C3%A1chira | Bolívar Municipality is one of the 29 municipalities that makes up the western Venezuelan state of Táchira and, according to a 2007 population estimate by the National Institute of Statistics of Venezuela, the municipality has a population of 60,149. The town of San Antonio del Táchira is the shiretown of the Bolívar Municipality.
Name
The municipality is one of several in Venezuela named "Bolívar Municipality" in honour of Venezuelan independence hero Simón Bolívar.
Demographics
The Bolívar Municipality, according to a 2007 population estimate by the National Institute of Statistics of Venezuela, has a population of 60,149 (up from 50,209 in 2000). This amounts to 5.1% of the state's population. The municipality's population density is .
Government
The mayor of the Bolívar Municipality is Juan Vicente Cañas Alviarez, elected on October 31, 2004, with 48% of the vote. He replaced Ramon Vivas shortly after the elections. The municipality is divided into four parishes; Bolívar, Palotal, Juan Vicente Gómez, and Isaías Medina Angarita (parishes Juan Vicente Gómez and Isaías Medina Angarita were officially separated from the Bolívar parish on January 25, 1995).
References
External links
bolivar-tachira.gob.ve
Information on the Bolívar Municipality
More information on the Bolívar Municipality
Municipalities of Táchira |
https://en.wikipedia.org/wiki/Response%20element | Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes.
Under conditions of stress, a transcription activator protein binds to the response element and stimulates transcription. If the same response element sequence is located in the control regions of different genes, then these genes will be activated by the same stimuli, thus producing a coordinated response.
Hormone response element
A hormone response element (HRE) is a short sequence of DNA within the promoter of a gene, that is able to bind to a specific hormone receptor complex and therefore regulate transcription. The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer. Specifically, HRE responds to steroid hormones, as the activated steroid receptor is the transcription factor binding HRE. This regulates the transcription of genes signalled by the steroid hormone.
A gene may have many different response elements, allowing complex control to be exerted over the level and rate of transcription.
HRE are used in transgenic animal cells as inducers of gene expression.
Examples of HREs include estrogen response elements and androgen response elements.
Examples
Examples of response elements include:
Nuclear receptor response elements – two 6-meric repeats for dimeric binding
Type 2 NR response elements: direct |
https://en.wikipedia.org/wiki/Tomb%20Raider%3A%20Underworld | Tomb Raider: Underworld is an action-adventure video game developed by Crystal Dynamics and published by Eidos Interactive for Windows, PlayStation 3, Xbox 360, Wii and Nintendo DS in November 2008. Later versions were released for mobile in December 2008, PlayStation 2 in 2009, and OS X in 2012. Various companies ported or developed the different versions. The ninth overall entry in the Tomb Raider series and third in the Legend trilogy, Underworld follows archaeologist-adventurer Lara Croft as she searches for Mjolnir, an artefact key to entering the realm of Helheim, while confronting adversaries from her past. Gameplay features Lara navigating levels set across the world through platforming, fighting enemies and solving puzzles to progress.
Production of Underworld began in 2006 following the release of Tomb Raider: Legend, and was developed in parallel with Anniversary (2007). The scenario was co-written by director Eric Lindstrom and series co-creator Toby Gard; Gard left Crystal Dynamics the following year. The gameplay was redesigned around a principle of Lara's abilities, with her actions created using motion capture for the first time. A new game engine was created for the project, with the team having troubles transitioning onto next-generation hardware and staff shortages due to production of Anniversary.
Announced in January 2008 for next-generation hardware, it was delayed into November and also announced for then-current generation hardware. 360-exclusive dow |
https://en.wikipedia.org/wiki/Phospholipase%20C | Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.
There are thirteen kinds of mammalian phospholipase C that are classified into six isotypes (β, γ, δ, ε, ζ, η) according to structure. Each PLC has unique and overlapping controls over expression and subcellular distribution.
Variants
Mammalian variants
The extensive number of functions exerted by the PLC reaction requires that it be strictly regulated and able to respond to multiple extra- and intracellular inputs with appropriate kinetics. This need has guided the evolution of six isotypes of PLC in animals, each with a distinct mode of regulation. The pre-mRNA of PLC can also be subject to differential splicing such that a mammal may have up to 30 PLC enzymes.
beta: PLCB1, PLCB2, PLCB3, PLCB4
gamma: PLCG1, PLCG2
delta: PLCD1, PLCD3, PLCD4
epsilon: PLCE1
eta: PLCH1, PLCH2
zeta: PLCZ1
phosp |
https://en.wikipedia.org/wiki/Brennilis | Brennilis (; ) is a commune in the Finistère department of Brittany in northwestern France.
Geography
Climate
Brennilis has a oceanic climate (Köppen climate classification Cfb). The average annual temperature in Brennilis is . The average annual rainfall is with January as the wettest month. The temperatures are highest on average in July, at around , and lowest in February, at around . The highest temperature ever recorded in Brennilis was on 8 August 2003; the coldest temperature ever recorded was on 12 January 1987.
Population
Inhabitants of Brennilis are called Brennilisiens in French.
See also
Communes of the Finistère department
Brennilis Nuclear Power Plant
Parc naturel régional d'Armorique
Roland Doré sculptor
References
External links
Official website
Mayors of Finistère Association
Communes of Finistère |
https://en.wikipedia.org/wiki/Edern%2C%20Finist%C3%A8re | Edern (; ) is a commune in the Finistère department of Brittany in northwestern France.
Geography
Climate
Edern has a oceanic climate (Köppen climate classification Cfb). The average annual temperature in Edern is . The average annual rainfall is with January as the wettest month. The temperatures are highest on average in August, at around , and lowest in January, at around . The highest temperature ever recorded in Edern was on 9 August 2003; the coldest temperature ever recorded was on 2 January 1997.
Population
Inhabitants of Edern are called in French Édernois.
See also
Communes of the Finistère department
References
External links
Official website
Mayors of Finistère Association
Communes of Finistère |
https://en.wikipedia.org/wiki/Interferon%20alfa-2b | Interferon alfa-2b is an antiviral or antineoplastic drug. It is a recombinant form of the protein Interferon alpha-2 that was originally sequenced and produced recombinantly in E. coli in the laboratory of Charles Weissmann at the University of Zurich, in 1980. It was developed at Biogen, and ultimately marketed by Schering-Plough under the trade name Intron-A. It was also produced in 1986 in recombinant human form, in the Center for Genetic Engineering and Biotechnology of Havana, Cuba, under the name Heberon Alfa R.
It has been used for a wide range of indications, including viral infections and cancers. This drug is approved around the world for the treatment of chronic hepatitis C, chronic hepatitis B, hairy cell leukemia, Behçet's disease, chronic myelogenous leukemia, multiple myeloma, follicular lymphoma, carcinoid tumor, mastocytosis and malignant melanoma.
The medication is being used in clinical trials to treat patients with SARS-CoV-2 and there are published results in the peer-reviewed scientific literature.
So far, two non-peer reviewed research articles have been published. One study at the University of Texas Medical Branch, Galveston, showed evidence of a direct anti-viral effect of Interferon alpha against novel Coronavirus in vitro. The study demonstrated around 10,000 fold reduction in the quantity of virus that was pre-treated with Interferon alpha 48 hours earlier. A second study by universities in China, Australia and Canada analysed 77 moderate COVI |
https://en.wikipedia.org/wiki/Phibro | Phibro is a global low carbon commodity company focused on renewable assets' development, acquisition, optimization, and related contract structuring. Phibro's headquarters are located in Stamford, Connecticut.
History
The origin of the company traces to 1901 when Julius Philipp, an Orthodox Jew, founded a small metal trading company in Hamburg, Germany and then in 1909, Philipp's younger brother, Oscar Philipp established a metal trading company in London under the name of Philipp Brothers. Julius continued to run the German operation out of Hamburg. In 1914, with the advent of World War I, Siegfried Bendheim, an apprentice, German citizen, and minor partner, avoided internment by the British government by moving to New York City where he established Philipp Brothers, Inc. while Oscar Philipp continued to operate the London office as he had previously obtained British citizenship. In 1923, another apprentice and second cousin to Bendheim, Siegfried Ullmann, moved to the New York office where he and Bendheim served as general partners with a minority interest held by London. Responsibilities in New York were divided with Bendheim responsible for chemicals and Ullmann for metals, scrap, and ore including their mining operations in Bolivia. In 1934, Julius moved Philipp Brothers' German operations to Amsterdam due to the rise of Nazi Germany (Julius perished in 1944 in the Bergen-Belsen concentration camp). The New York office eventually became Philipp Brothers headquarters |
https://en.wikipedia.org/wiki/Zinc-dependent%20phospholipase%20C | In molecular biology, zinc-dependent phospholipases C is a family of bacterial phospholipases C enzymes, some of which are also known as alpha toxins.
Bacillus cereus contains a monomeric phospholipase C (PLC) of 245 amino-acid residues. Although PLC prefers to act on phosphatidylcholine, it also shows weak catalytic activity with sphingomyelin and phosphatidylinositol. Sequence studies have shown the protein to be similar both to alpha toxin from Clostridium perfringens and Clostridium bifermentans, a phospholipase C involved in haemolysis and cell rupture, and to lecithinase from Listeria monocytogenes, which aids cell-to-cell spread by breaking down the 2-membrane vacuoles that surround the bacterium during transfer.
Each of these proteins is a zinc-dependent enzyme, binding 3 zinc ions per molecule. The enzymes catalyse the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate.
In Bacillus cereus, there are nine residues known to be involved in binding the zinc ions: 5 His, 2 Asp, 1 Glu and 1 Trp. These residues are all conserved in the Clostridium alpha-toxin.
Some examples of this enzyme contain a C-terminal sequence extension that contains a PLAT domain which is thought to be involved in membrane localisation.<ref
name="PUB00018111"></ref>
References
EC 3.1.4
Protein domains
Peripheral membrane proteins
Zinc proteins |
https://en.wikipedia.org/wiki/William%20Winstanley | William Winstanley (c. 1628 – 1698) was an English poet and compiler of biographies.
Life
Born about 1628, William Winstanley was the second son of William Winstanley of Quendon, Essex, (d. 1687) by his wife Elizabeth. Henry Winstanley was his nephew. William was sworn in as a freeman of Saffron Walden on 21 April 1649. He was for a time a barber in London (Wood, Athenae Oxon. ed. Bliss, iv. 763), but he soon relinquished the razor for the pen. "The scissors, however, he retained, for he borrowed without stint, and without acknowledgement also, from his predecessors", Much of his literary work commemorates his connection with Essex.
He published under his own name a poem called 'Walden Bacchanals,' and he wrote an elegy on Anne, wife of Samuel Gibs of Newman Hall, Essex (Muses' Cabinet). There is little doubt that most of the almanacs and chapbooks issued from 1662 onwards under the pseudonym of "Poor Robin" came from his pen. He was a staunch royalist after the Restoration, although in 1659 he wrote a fairly impartial notice of Oliver Cromwell (cf. England's Worthies). "He is a fantastical writer, and of the lower class of our biographers; but we are obliged to him for many notices of persons went away for a time and stayed in cambridge, east london and things which are recorded only in his works" (Granger, Biog. Hist. of Engl. 5th ed. v. 271), His verse is usually boisterous doggerel in the manner of John Taylor (1580–1663) the water-poet. Winstanley was buried at Quendo |
https://en.wikipedia.org/wiki/Extraneous%20and%20missing%20solutions | In mathematics, an extraneous solution (or spurious solution) is a solution, such as that to an equation, that emerges from the process of solving the problem but is not a valid solution to the problem. A missing solution is a solution that is a valid solution to the problem, but disappeared during the process of solving the problem. Both are frequently the consequence of performing operations that are not invertible for some or all values of the variables, which prevents the chain of logical implications in the proof from being bidirectional.
Extraneous solutions: multiplication
One of the basic principles of algebra is that one can multiply both sides of an equation by the same expression without changing the equation's solutions. However, strictly speaking, this is not true, in that multiplication by certain expressions may introduce new solutions that were not present before. For example, consider the following equation:
If we multiply both sides by zero, we get,
This is true for all values of x, so the solution set is all real numbers. But clearly not all real numbers are solutions to the original equation. The problem is that multiplication by zero is not invertible: if we multiply by any nonzero value, we can reverse the step by dividing by the same value, but division by zero is not defined, so multiplication by zero cannot be reversed.
More subtly, suppose we take the same equation and multiply both sides by x. We get
This quadratic equation has two solutions, |
https://en.wikipedia.org/wiki/CBV%20%28chemotherapy%29 | CBV refers to Cytoxan (cyclophosphamide), BCNU (carmustine), and VP-16 (etoposide), three drugs in a chemotherapy regimen commonly given to lymphoma patients in conjunction with stem cell therapy.
CBV is usually given in high doses to patients who have relapsed or who have refractory disease and cannot benefit from standard chemotherapy. Since a patient's bone marrow is virtually guaranteed not to survive a course of CBV, the receiving patient must receive a transplant (allogeneic or autologous, depending on his or her condition) of stem cells (formerly referred to as a bone marrow transplant) to replace the patient's own hemopoietic ("blood-forming") stem cells.
See also
Cancer
Chemotherapy
Lymphoma
Stem cells
Bone marrow transplant
References
CBV |
https://en.wikipedia.org/wiki/Simplified%20sewerage | Simplified sewerage, also called small-bore sewerage, is a sewer system that collects all household wastewater (blackwater and greywater) in small-diameter pipes laid at fairly flat gradients. Simplified sewers are laid in the front yard or under the pavement (sidewalk) or - if feasible - inside the back yard, rather than in the centre of the road as with conventional sewerage. It is suitable for existing unplanned low-income areas, as well as new housing estates with a regular layout. It allows for a more flexible design. With simplified sewerage it is crucial to have management arrangements in place to remove blockages, which are more frequent than with conventional sewers. It has been estimated that simplified sewerage reduces investment costs by up to 50% compared to conventional sewerage.
Simplified sewerage is sometimes also referred to as conventional sewerage with appropriate standards, implying that most conventional sewers are overdesigned.
The concept of simplified sewerage emerged in parallel in Natal, Brazil and Karachi, Pakistan in the early 1980s without any interaction or communication.
In both cases particular emphasis was given to community mobilization, an essential element for the success of simplified sewerage. In Latin America, and particularly in Brazil, simplified sewerage is also known as condominial sewerage, a term that underscores the importance of community participation in planning and maintenance at the level of a housing block (known as cond |
https://en.wikipedia.org/wiki/Ch%C3%A2teau%20Valandraud | Château Valandraud, or Château de Valandraud, is Bordeaux wine producer situated in the Saint-Émilion appellation, promoted to Premier Grand Cru Classé in the 2012 Classification of Saint-Emilion wine. The winery is located on the Right Bank of France’s Bordeaux wine region in the commune of Saint-Émilion.
The winery also produces the second wines, Virginie de Valandraud and 3 de Valandraud, and the Kosher wine Château Valandraud Kosher.
History
In 1989 Jean-Luc Thunevin and his wife Murielle Andraud bought a plot in Saint-Émilion near Château Pavie-Macquin. Further plots in the region were acquired over the years, in locations such as Saint-Sulpice-de-Faleyrens and Saint-Étienne-de-Lisse, and a former garage to be used as a winery, releasing the first vintage in 1991 of 1,500 bottles priced at €13. Exemplified as a typical "microchâteau", Thunevin is closely associated with the "garagiste" movement, and the wine is described as the pioneer "Vin de garage". In 1995, Valandraud was given a better rating by Robert Parker than Château Pétrus, and by 1997 the Valandraud bottle price was set at €91. The 2005 vintage was set at €165.
The Thunevins have since taken on several projects, including the first "garage wine"' of Médoc, Marojallia, and acting as négociant distributor for several estates from Bordeaux, Languedoc-Roussillon and elsewhere, including Château Ausone, Gracia, Harlan Estate and Dominio de Pingus.
Jean-Luc Thunevin is among the wine personalities satirised n |
https://en.wikipedia.org/wiki/LDK%20Solar%20Co | LDK Solar Co. Ltd., located in Xinyu City, Jiangxi province in the People's Republic of China, manufactures multicrystalline solar wafers used in solar cells, and provides wafering services for both monocrystalline and multicrystalline wafers. Their distribution network for solar products covered over 43 distributors and wholesalers across 15 countries.
LDK filed for Chapter 11 bankruptcy in 2014.
LDK and its Chinese subsidiaries were forced into bankruptcy in 2015.
History
Founding
Xiaofeng Peng founded LDK Solar in July 2005 and is its chairman and chief executive officer. Mr. Peng first founded Suzhou Liouxin in March 1997, and was its chief executive officer until February 2006. Suzhou Liouxin manufactured personal protective equipment products like gloves and employed 12,000. He considered adding solar cell wafers to its product line when he realized that no Chinese company was producing them. In 2005, Peng invested $30 million of his own money and $80 million of venture financing into building factories.
Production
LDK stated an annualized solar wafer capacity of 1.46 GW at the end of 2008, and 3GW at the end of 2010.
LDK contracted with Fluor Corp., an American engineering firm, for construction of a 15,000 Ton per Year polysilicon plant. The first 5000-ton train went into production in July 2009, with the second 5000 train scheduled for Q3 and third and final train by the end of 2010.
A Second, 1000 Ton per Year Polysilicon Plant was Bought by LDK from Sunway |
https://en.wikipedia.org/wiki/Anzo%C3%A1tegui%20Municipality | The Anzoátegui Municipality is one of the nine municipalities (municipios) that makes up the Venezuelan state of Cojedes and, according to the 2011 census by the National Institute of Statistics of Venezuela, the municipality has a population of 17,030. The town of Cojedes is the shire town of the Anzoátegui Municipality.
Demographics
The Anzoátegui Municipality, according to a 2007 population estimate by the National Institute of Statistics of Venezuela, has a population of 16,333 (up from 14,354 in 2000). This amounts to 5.4% of the state's population. The municipality's population density is .
Government
The mayor of the Anzoátegui Municipality is Luis Linares, re-elected on October 31, 2004, with 44% of the vote. The municipality is divided into two parishes; Cojedes and Juan de Mata Suárez.
References
External links
anzoategui-cojedes.gob.ve
Municipalities of Cojedes (state) |
https://en.wikipedia.org/wiki/City%20Solar | City Solar AG is a producer of large-scale photovoltaic power plants, taking care of all aspects of production. This includes site location, planning, construction, and management. The company was started in 2002 in Bad Kreuznach, Germany, but now has offices in Saarbrücken, Berlin, Chemnitz, Augsburg, and Madrid.
City Solar has produced over a dozen power stations including the world's largest photovoltaic power plant located in Beneixama, Spain. The Beneixama photovoltaic power plant is a 10MWp power station, with 100,000 solar modules, encompassing an area of approximately 500,000m2 As of 2007, City Solar has 4 more plants under construction or in development.
See also
Photovoltaic power stations
List of photovoltaics companies
References
Solar energy companies of Germany
Photovoltaics manufacturers |
https://en.wikipedia.org/wiki/Hardy%E2%80%93Ramanujan%20theorem | In mathematics, the Hardy–Ramanujan theorem, proved by Ramanujan and checked by Hardy states that the normal order of the number ω(n) of distinct prime factors of a number n is log(log(n)).
Roughly speaking, this means that most numbers have about this number of distinct prime factors.
Precise statement
A more precise version states that for every real-valued function ψ(n) that tends to infinity as n tends to infinity
or more traditionally
for almost all (all but an infinitesimal proportion of) integers. That is, let g(x) be the number of positive integers n less than x for which the above inequality fails: then g(x)/x converges to zero as x goes to infinity.
History
A simple proof to the result was given by Pál Turán, who used the Turán sieve to prove that
Generalizations
The same results are true of Ω(n), the number of prime factors of n counted with multiplicity.
This theorem is generalized by the Erdős–Kac theorem, which shows that ω(n) is essentially normally distributed.
References
Theorems in analytic number theory
Theorems about prime numbers |
https://en.wikipedia.org/wiki/HutP | HutP (Histidine utilizing Protein) is one of the anti-terminator proteins of Bacillus subtilis, which is responsible for regulating the expression of the hut structural genes of this organism in response to changes in the intracellular levels of L-histidine and divalent metal ions. In the hut operon, HutP is located just downstream from the promoter, while the five other subsequent structural genes, hutH, hutU, hutI, hutG and hutM, are positioned far downstream from the promoter. In the presence of L-histidine and divalent metal ions, HutP binds to the nascent hut mRNA leader transcript. This allows the anti-terminator to form, thereby preventing the formation of the terminator and permitting transcriptional read-through into the hut structural genes. In the absence of L-histidine and divalent metal ions or both, HutP does not bind to the hut mRNA, thus allowing the formation of a stem loop terminator structure within the nucleotide sequence located between the hutP and structural genes.
HutP is a 16.2 kDa protein consisting of 148 amino acid residues. HutP also exists in five other Bacillus species, including B. anthracis, B. cereus, B. halodurans, B. thuringiensis, and Geobacillus kautophilus, with 60% sequence identity. Thirumananseri Kumarevel solved the crystal structure of the HutP protein in the apo-form, binary complex (complexed with divalent metal ions or L-histidine), ternary complex (HutP-metal ions-L-histidine) and quaternary complexes (HutP-L-histidine- |
https://en.wikipedia.org/wiki/Myrophine | Myrophine (Myristylbenzylmorphine) is an opiate analogue that was developed in 1952. It is a derivative of morphine.
Myrophine is substituted with a 3-benzyl group and a 6-myristyl chain. It is metabolised to form benzylmorphine and then further to morphine, and so is a long-acting prodrug for morphine, but with a slow onset of effects. It is weaker than morphine as an analgesic but longer-lasting in effects, and was thought to have more local anesthetic effect than morphine, though with a somewhat greater tendency to cause reactions like itching and rash. In addiction studies conducted in human subjects in the 1950s, myrophine did not substitute for morphine in withdrawal, did not produce notable morphine-like effects, and did not produce addiction or dependence regardless of dose or how it was administered. Consequently, it was thought to be useful in treating pain in addicts who were being detoxified from other opioid drugs.
It is a Schedule I drug in the US, considered to have high potential for abuse and no medical applications, and is controlled under international drug conventions. Myrophine is almost invariably used as the hydrochloride (free base conversion ratio 0.94) and has a DEA Administrative Controlled Substance Control Number of 9308.
Myrophine is a Class A controlled substance in the UK, and is on the UN's Yellow list.
References
4,5-Epoxymorphinans
Phenol ethers
Carboxylate esters
Mu-opioid receptor agonists
Semisynthetic opioids
Benzyl compounds |
https://en.wikipedia.org/wiki/Prefix%20header | In computer programming, a prefix header is a feature found in some C or C++ compilers used to ensure that a certain snippet of code is inserted at the beginning of every file.
Overview
In the C and C++ programming languages, a header file is a file whose text is included in another source file by the compiler, usually by the use of compiler directives at the beginning of the source file. A prefix header differs from a normal header file in that it is automatically included at the beginning of every source file by the compiler, without the use of any compiler directives.
Prefix headers are usually pre-compiled in order to reduce compilation times. Use of prefix headers outside of this purpose can make your code more difficult to maintain & less re-usable.
Prefix headers can also be used for cross-platform support. On *NIX systems, it is common to have a config.h header file generated at build time (via something like autoconf) that describes the capabilities of the system. However, when using certain build systems such as Visual Studio or Xcode, this config.h may be unavailable. One technique to solve this is to have HAVE_CONFIG_H be a pre-defined macro in the build-system that generates a config.h so that code knows whether it needs to #include config.h (& is safe for use by build systems that do not have it). An alternative, would be for the build system to add config.h as a prefix header instead of defining HAVE_CONFIG_H. Of course the downside is that this heade |
https://en.wikipedia.org/wiki/Bland%27s%20rule | In mathematical optimization, Bland's rule (also known as Bland's algorithm, Bland's anti-cycling rule or Bland's pivot rule) is an algorithmic refinement of the simplex method for linear optimization.
With Bland's rule, the simplex algorithm solves feasible linear optimization problems without cycling.
The original simplex algorithm starts with an arbitrary basic feasible solution, and then changes the basis in order to decrease the minimization target and find an optimal solution. Usually, the target indeed decreases in every step, and thus after a bounded number of steps an optimal solution is found. However, there are examples of degenerate linear programs, on which the original simplex algorithm cycles forever. It gets stuck at a basic feasible solution (a corner of the feasible polytope) and changes bases in a cyclic way without decreasing the minimization target.
Such cycles are avoided by Bland's rule for choosing a column to enter and a column to leave the basis.
Bland's rule was developed by Robert G. Bland, now an Emeritus Professor of operations research at Cornell University, while he was a research fellow at the Center for Operations Research and Econometrics in Belgium.
Algorithm
One uses Bland's rule during an iteration of the simplex method to decide first what column (known as the entering variable) and then row (known as the leaving variable) in the tableau to pivot on. Assuming that the problem is to minimize the objective function, the algorithm is l |
https://en.wikipedia.org/wiki/Interferon%20gamma%20receptor%201 | Interferon gamma receptor 1 (IFNGR1) also known as CD119 (Cluster of Differentiation 119), is a protein that in humans is encoded by the IFNGR1 gene.
Function
The gene IFNGR1 encodes IFN-γR1, which is the ligand-binding chain (alpha) of the heterodimeric gamma interferon receptor, which is found on macrophages. IFNGR2, encodes IFN-γR2, the non-ligand-binding partner of the heterodimeric receptor.
Interactions
Interferon gamma receptor 1 has been shown to interact with Interferon-gamma.
Mutations
Mutations in the IFNGR1 gene can lead to extreme susceptibility to Mycobacterial infections. All known mutations and common variations in the IFNGR1 are present in the IFNGR1 mutation database.
See also
Cluster of differentiation
Interferon-gamma receptor
References
Further reading
External links
Clusters of differentiation |
https://en.wikipedia.org/wiki/Gardein | Gardein (a portmanteau of garden and protein) is a line of meat-free foods produced by Conagra Brands. In 2003, the company was founded by Yves Potvin, who remained as the CEO of Gardein until 2016. In November 2014, Pinnacle Foods purchased Gardein for $154 million. Pinnacle was acquired by Conagra in 2018.
The company has production facilities in Richmond, British Columbia and Hagerstown, Maryland. All of Gardein's products are vegan. The company uses a proprietary process to make its meatless products. In 2014, the company began producing gluten free meatless products.
History
Garden Protein International was founded by former chef Yves Potvin in 2003. In 2009, the company began selling its frozen products.
In 2007, Garden Protein had 85 employees and $50 million in annual sales. In 2014, it had nearly $100 million in sales at the retail level. By 2015, it had over 250 employees with distribution to more than 22,000 stores in North America.
Gardein was first used in the United Kingdom in 2008, as an ingredient in Grassington's frozen meals.
Publicity
Gardein products have been featured on The Oprah Winfrey Show multiple times by chef and Gardein consultant Tal Ronnen.
In 2013, Gardein partnered with the Los Angeles City Council to celebrate Meatless Monday.
Awards
In 2007, Gardein received PETA's Company of the Year Award for their meat substitute products.
Since 2010 Gardein has received four Canadian Grand Prix New Product awards (Frozen or Refrigerated Pre |
https://en.wikipedia.org/wiki/Ayacucho%20Municipality%2C%20T%C3%A1chira | The Ayacucho Municipality is one of the 29 municipalities that makes up the western Venezuelan state of Táchira and, according to a 2007 population estimate by the National Institute of Statistics of Venezuela, the municipality has a population of 60,454. The town of Colón is the municipal seat of the Ayacucho Municipality.
Demographics
The Ayacucho Municipality, according to a 2007 population estimate by the National Institute of Statistics of Venezuela, has a population of 60,454 (up from 50,992 in 2000). This amounts to 5.1% of the state's population. The municipality's population density is .
Government
The mayor of the Ayacucho Municipality is Gabino Paz Guerrero, re-elected on October 31, 2004, with 47% of the vote. The municipality is divided into three parishes; Ayacucho, Rivas Berti, San Pedro del Río.
References
External links
ayacucho-tachira.gob.ve
Municipalities of Táchira |
https://en.wikipedia.org/wiki/Glisodin | Glisodin is the registered trademark of a nutritional supplement based on two constituents:
Cantaloupe extract, which typically contains high quantities of the enzyme superoxide dismutase (SOD)
Gliadin, a wheat protein designed to protect SOD during the digestive process
Background
As oxygen metabolizes in the body, potentially harmful reactive oxygen species (ROS) are created. The human body implements an antioxidant defense system to protect against ROS. In the event that these defenses are overpowered by the ROS, cell damage results (which is a major cause of aging in the body).
Superoxide dismutase (SOD) helps to slow the creation of ROS, ultimately playing a key role in the defense against cell damage. However, due to a very fragile molecular structure, it is particularly prone to damage from stomach acids and digestive enzymes when taken orally. Gliadin, which is well known as a carrier protein for controlled drug release, helps to protect SOD.
Research
A wide range of clinical research has been undertaken to study glisodin's antioxidant capacities. This has extended into a wide range of applications, including protection from ultraviolet radiation, athletic performance, cardiovascular health, ischemia and reperfusion injury.
A group of researchers in France and Germany led by Dr. Claus Muth concluded that glisodin is helpful in protecting against DNA damage caused by hyperbaric oxidation. A 2005 study at Rutgers University also concluded that glisodin is hel |
https://en.wikipedia.org/wiki/Thalmann%20algorithm | The Thalmann Algorithm (VVAL 18) is a deterministic decompression model originally designed in 1980 to produce a decompression schedule for divers using the US Navy Mk15 rebreather. It was developed by Capt. Edward D. Thalmann, MD, USN, who did research into decompression theory at the Naval Medical Research Institute, Navy Experimental Diving Unit, State University of New York at Buffalo, and Duke University. The algorithm forms the basis for the current US Navy mixed gas and standard air dive tables (from US Navy Diving Manual Revision 6). The decompression model is also referred to as the Linear–Exponential model or the Exponential–Linear model.
History
The Mk15 rebreather supplies a constant partial pressure of oxygen of with nitrogen as the inert gas. Prior to 1980 it was operated using schedules from printed tables. It was determined that an algorithm suitable for programming into an underwater decompression monitor (an early dive computer) would offer advantages. This algorithm was initially designated "MK15 (VVAL 18) RTA", a real-time algorithm for use with the Mk15 rebreather.
Description
VVAL 18 is a deterministic model that utilizes the Naval Medical Research Institute Linear Exponential (NMRI LE1 PDA) data set for calculation of decompression schedules. Phase two testing of the US Navy Diving Computer produced an acceptable algorithm with an expected maximum incidence of decompression sickness (DCS) less than 3.5% assuming that occurrence followed the binomial |
https://en.wikipedia.org/wiki/Jenssen | Jenssen is a Norwegian patronymic surname meaning "son of Jens". The prefix "Jens-" is a Danish and Frisian derivative of Johannes. There are alternate spellings, including the Danish Jensen, the English language Jenson, and the Belgian/Dutch language Janson. Jenssen is uncommon as a given name. People with the name Jenssen include:
Amanda Jenssen (born 1988), Swedish singer
Elois Jenssen (1922-2004), American film and television costume designer
Geir Jenssen, Norwegian musician best known under the recording name Biosphere
Hans Jørgen Darre-Jenssen (1864-1950), Norwegian politician
Hans Wiers-Jenssen (1866–1925), Norwegian novelist
Jens Martin Arctander Jenssen (1885-1968), Norwegian politician
Jens Peter Book-Jenssen (1910–1999), Norwegian singer
Johan Henrik Wiers-Jenssen (1897–1951), Norwegian newspaper columnist
Lauritz Jenssen (1837–1899), Norwegian businessperson and politician
Lauritz Dorenfeldt Jenssen (1801–1859), Norwegian businessperson
Leif Jenssen, Norwegian weightlifter
Lene Jenssen, Norwegian swimmer
Matz Jenssen (1760–1813), Norwegian businessperson
Ruben Yttergård Jenssen, Norwegian footballer
Worm Hirsch Darre-Jenssen (1870-1945), Norwegian politician
See also
Jens (disambiguation)
Jensen (disambiguation)
Jenson (disambiguation)
Janson (disambiguation)
Norwegian-language surnames
Germanic-language surnames
Surnames of Frisian origin
Patronymic surnames |
https://en.wikipedia.org/wiki/APBB1 | Amyloid beta A4 precursor protein-binding family B member 1 is a protein that in humans is encoded by the APBB1 gene.
Function
The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants have been described for this gene but some of their full length sequence is not known.
Interactions
APBB1 has been shown to interact with APLP2, TFCP2, LRP1 and Amyloid precursor protein.
References
External links
Further reading
Proteins |
https://en.wikipedia.org/wiki/ERCC6 | DNA excision repair protein ERCC-6 (also CS-B protein) is a protein that in humans is encoded by the ERCC6 gene. The ERCC6 gene is located on the long arm of chromosome 10 at position 11.23.
Having 1 or more copies of a mutated ERCC6 causes Cockayne syndrome, type II.
Function
DNA can be damaged by ultraviolet radiation, toxins, radioactive substances, and reactive biochemical intermediates like free radicals. The ERCC6 protein is involved in repairing the genome when specific genes undergoing transcription (dubbed active genes) are inoperative; as such, ERCC6 serves as a transcription-coupled excision repair protein, being one of the fundamental enzymes in active gene repair.
Structure and Mechanism
CSB has been found to exhibit ATPase properties; there are contradictory publications regarding the effect of ATP concentration on CSB's activity. The most recent evidence suggests that ADP/AMP allosterically regulate CSB. As such, it has been speculated that CSB may promote protein complex formation at repair sites subject to the ATP to ADP charge ratio.
Conservation of helicase motifs in eukaryote CSB is evident; all seven major domains of the protein are conserved among numerous RNA and DNA helicases. Detailed structural analysis of CSB has been performed; motifs I, Ia, II, and III are collectively called domain 1, while motifs IV, V, and VI comprise domain 2. These domains wrap around an interdomain cleft involved in ATP binding and hydrolysis. Motifs III and IV are i |
https://en.wikipedia.org/wiki/FANCD2 | Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2 (this gene), FANCE, FANCF, FANCG, FANCI , FANCJ, FANCL, FANCM, FANCN and FANCO.
Function
Fanconi anemia is a disorder with a recessive Mendelian pattern of inheritance characterized by chromosomal instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquitinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 and BRCA2) involved in homology-directed DNA repair (see Figure: Recombinational repair of DNA double-strand damages). A nuclear complex containing FANCA, [Fanconi anemia, complementation group A], FANCB, FANCC, FANCE, FANCF, FANCL and FANCG proteins is required for the activation of the FANCD2 protein to the mono-ubiquitinated isoform.
Mono-ubiquination of FANCD2 is essential for repairing DNA interstrand crosslinks, and clamps the protein on DNA together with its partner protein FANCI. The monoubiquitinated FANCD2:FANCI complex coats DNA in a filament-like array, potentially as a way to protect DNA a |
https://en.wikipedia.org/wiki/G6PC | Glucose-6-phosphatase, catalytic subunit (glucose 6-phosphatase alpha) is an enzyme that in humans is encoded by the G6PC gene.
Glucose-6-phosphatase is an integral membrane protein of the endoplasmic reticulum that catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose and orthophosphate. It is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis. Defects in the enzyme cause glycogen storage disease type I (von Gierke disease).
Interactive pathway map
See also
G6PC2
G6PC3
glucose 6-phosphatase
glycogen storage disease type I
References
Further reading |
https://en.wikipedia.org/wiki/GRIA1 | Glutamate receptor 1 is a protein that in humans is encoded by the GRIA1 gene.
Function
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The GRIA1 belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Each of the members (GRIA1–4) include flip and flop isoforms generated by alternative RNA splicing. The receptor subunits encoded by each isoform vary in their signal transduction properties. The isoform presented here is the flop isoform. In situ hybridization experiments showed that human GRIA1 mRNA is present in granule and pyramidal cells in the hippocampal formation.
GRIA1 (GluR1) is centrally involved in synaptic plasticity. Expression of the GluR1 gene is significantly reduced in the human frontal cortex with increasing age.
Interactions
GRIA1 has been shown to interact with:
DLG1
EPB41L2, and
GRID2.
See also
AMPA receptor
References
Further reading
External links
Ionotropic glutamate receptors |
https://en.wikipedia.org/wiki/GTF2I | General transcription factor II-I is a protein that in humans is encoded by the GTF2I gene.
Function
This gene encodes a multifunctional phosphoprotein, TFII-I, with roles in transcription and signal transduction. Haploinsuffiency (deletion of one copy) of the GTF2I gene is noted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. It is duplicated in the 7q11.23 duplication syndrome. The exon(s) encoding 5' UTR has not been fully defined, but this gene is known to contain at least 34 exons, and its alternative splicing generates 4 transcript variants in humans. A single gain-of-function point mutation in GTF2I is also found in certain Thymomas. Single nucleotide polymorphism (SNP) in GTF2I is correlated to autoimmune disorders.
Interactions
GTF2I has been shown to interact with:
Bruton's tyrosine kinase,
HDAC3,
Histone deacetylase 2,
MAPK3,
Myc,
PRKG1,
Serum response factor and
USF1 (human gene).
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Glycophorin%20A | Glycophorin A (MNS blood group), also known as GYPA, is a protein which in humans is encoded by the GYPA gene. GYPA has also recently been designated CD235a (cluster of differentiation 235a).
Function
Glycophorins A (GYPA; this protein) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB.
Genomics
GypA, GypB and GypE are members of the same family and are located on the long arm of chromosome 4 (chromosome 4q31). The family evolved via two separate gene duplication events. The initial duplication gave rise to two genes one of subsequently evolved into GypA and the other which give rise via a second duplication event to GypB and GypE. These events appear to have occurred within a relatively short time span. The second duplication appears to have occurred via an unequal crossing over event.
The GypA gene itself consists of 7 exons and has 97% sequence homology with GypB and GypE from the 5' untranslated transcription region (UTR) to the coding sequence encoding the first 45 amino acids. The exo |
https://en.wikipedia.org/wiki/Interleukin%201%20receptor%2C%20type%20I | Interleukin 1 receptor, type I (IL1R1) also known as CD121a (Cluster of Differentiation 121a), is an interleukin receptor. IL1R1 also denotes its human gene.
The protein encoded by this gene is a cytokine receptor that belongs to the interleukin-1 receptor family. This protein is a receptor for interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), and interleukin 1 receptor antagonist (IL1RA). It is an important mediator involved in many cytokine induced immune and inflammatory responses. This gene along with interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 2 (IL1RL2), and interleukin 1 receptor-like 1 (IL1RL1) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12.
Interactions
Interleukin 1 receptor, type I has been shown to interact with PIK3R1, Myd88 and IL1RAP.
See also
Cluster of differentiation
Interleukin 1 receptor, type II
References
Further reading
External links
Clusters of differentiation |
https://en.wikipedia.org/wiki/ING1 | Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene.
Function
This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that physically interacts with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. Reduced expression and rearrangement of this gene have been detected in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported.
Location on Chromosome 13
ING1 is located near the following genes on Chromosome 13
CARKD Carbohydrate Kinase Domain-Containing Protein (Unknown Function)
COL4A2: A2 Subunit of type IV collagen
RAB20: Potential regulator of Connexin 43 trafficking.
CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
Interactions
ING1 has been shown to interact with:
CREB binding protein,
DMAP1,
HDAC1,
P53,
PCNA,
SAP30,
SIN3A,
SMARCA4, and
SMARCC1.
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/MAX%20%28gene%29 | MAX (also known as myc-associated factor X) is a gene that in humans encodes the MAX transcription factor.
Function
The protein product of MAX contains the basic helix-loop-helix and leucine zipper motifs. It is therefore included in the bHLHZ family of transcription factors. It is able to form homodimers with other MAX proteins and heterodimers with other transcription factors, including Mad, Mxl1 and Myc. The homodimers and heterodimers compete for a common DNA target site (the E-box) in a gene promoter zone. Rearrangement of dimers (e.g., Mad:Max, Max:Myc) provides a system of transcriptional regulation with greater diversity of gene targets. Max must dimerise in order to be biologically active.
Transcriptionally active hetero- and homodimers involving Max can promote cell proliferation as well as apoptosis.
Interactions
The protein product of Max has been shown to interact with:
Myc,
MNT,
MSH2,
MXD1,
MXI1,
MYCL1,
N-Myc,
SPAG9,
TEAD1, and
Transformation/transcription domain-associated protein.
Clinical relevance
This gene has been shown mutated in cases of hereditary pheochromocytoma. More recently the Max gene becomes mutated and becomes inactivated in small cell lung cancer (SCLC). This is mutually exclusive with alterations at Myc and BRG1, the latter coding for an ATPase of the SWI/SNF complex. It was demonstrated that the BRG1 product regulates the expression of Max through direct recruitment to the Max promoter region, and that depletion of BRG1 s |
https://en.wikipedia.org/wiki/PRKCH | Protein kinase C eta type is an enzyme that in humans is encoded by the PRKCH gene.
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/Proteasome%20%28prosome%2C%20macropain%29%20subunit%2C%20alpha%201 | Proteasome subunit alpha type-1 is a protein that in humans is encoded by the PSMA1 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, and beta5i) that contributes to the complete assembly of 20S proteasome complex.
Structure
Protein expression
Th gene PSMA1 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. In a study of mouse gene PSMA1 which share 98% homology with human gene, the gene was isolated and cloned, and then identified as C2 subunit of the 20S proteasome (old nomenclature). The gene has 10 exons that are distributed over a 12kb region on mouse chromosome 7. The same study showed that mouse genes Psma1 and Pde3b are closely linked, residing between cM 53 and 53.3 in a region syntenic to human chromosome 11p15. The human protein proteasome subunit alpha type-1 is also known as 20S proteasome subunit alpha-6 (based on systematic nomenclature). The protein is 30 kDa in size and composed of 263 amino acids. The calculated theoretical pI of this protein is 6.15.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: The two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and be |
https://en.wikipedia.org/wiki/PSMA7 | Proteasome subunit alpha type-7 also known as 20S proteasome subunit alpha-4 is a protein that in humans is encoded by the PSMA7 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
Function
The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. As a component of alpha ring, proteasome subunit alpha type-7 contributes to the formation of heptameric alpha rings and substrate entrance gate. Importantly, this subunit plays a critical role in the assembly of 19S base and 20S. This particular subunit has been shown to interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. In addition, this subunit is involved in regulating hepatitis virus C internal ribosome entry site (IRES) activity, an activity essential for viral replication. This core alpha subunit is also involved in regulating the hypoxia-inducible factor-1alpha, a transcription factor important for cellular responses to oxygen tension. Recent study on underlying mechanisms of E3 ligase Parkin-related neurodegeneration identified this proteasome subuni |
https://en.wikipedia.org/wiki/PSMB5 | Proteasome subunit beta type-5 as known as 20S proteasome subunit beta-5 is a protein that in humans is encoded by the PSMB5 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "chymotrypsin-like" activity and is capable of cleaving after large hydrophobic residues of peptide. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.
Structure
Protein expression
The gene PSMB5 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit beta5i (proteasome beta 8 subunit). The gene has 5 exons and locates at chromosome band 14q11.2. The human protein proteasome subunit beta type-5 is 22 kDa in size and composed of 204 amino acids. The calculated theoretical pI of this protein is 8.66.
Comp |
https://en.wikipedia.org/wiki/PSMC1 | 26S protease regulatory subunit 4, also known as 26S proteasome AAA-ATPase subunit Rpt2, is an enzyme that in humans is encoded by the PSMC1 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. Six 26S proteasome AAA-ATPase subunits (Rpt1, Rpt2 (this protein), Rpt3, Rpt4, Rpt5, and Rpt6) together with four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13) form the base sub complex of 19S regulatory particle for proteasome complex.
Gene
The gene PSMC1 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. The human PSMC1 gene has 11 exons and locates at chromosome band 14q32.11.
Protein
The human protein 26S protease regulatory subunit 4 is 49kDa in size and composed of 440 amino acids. The calculated theoretical pI of this protein is 526S protease regulatory subunit 5.68. One expression isoform is generated by alternative splicing, in which 1-73 of the amino acid sequence is missing.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic acti |
https://en.wikipedia.org/wiki/S100-A1 | Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the S100A1 gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 has shown promise as an effective candidate for gene therapy to treat post-myocardially infarcted cardiac tissue.
Structure
S100A1 is a member of the S100 family of proteins expressed in cardiac muscle, skeletal muscle and brain, with highest density at Z-lines and sarcoplasmic reticulum. S100A1 contains 4 EF-hand calcium-binding motifs in its dimerized form, and can exist as either a hetero or homodimer. The S100A1 homodimer is high affinity (nanomolar range or tighter), and is formed through hydrophobic packing of an X-type 4-helix bundle created between helices 1, 1', 4, and 4'. Protein nuclear magnetic resonance spectroscopy structural information on the homodimeric form of this protein shows that each monomer is helical and contains two EF-hand calcium-binding loops; one in the N-terminus and a canonical EF hand in the C-terminus having higher calcium affinity (dissociation constant of roughly 20 micromolar). The two EF hand domains neighbor each other in three dimensional space, and are connected to each other through a short beta sheet region (residues 27–29 and 68–70).
Upon binding calcium, helix 3 of S100A1 re-orients from being relatively antiparallel to helix 4 to being roughly perpendicular. This conformational change is |
https://en.wikipedia.org/wiki/TNFAIP3 | Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene.
This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and a deubiquitinating enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The A20 protein is ancient, and protein homolog can be found as far back as cnidaria (corals, jellyfish, anemones) with a conserved protein domain composition. Using knockout mouse models of TNFAIP3 and its transcriptional repressor (i.e. KCHIP3), TNFAIP3 has been shown to be critical for limiting inflammation by terminating endotoxin- and TNF-induced NF-kappa B responses. In brief, deubiquitinase function of TNFAIP3 was shown to remove ubiquitin chains from VE-cadherin to prevent loss of VE-cadherin at the endothelial adherens junctions.
Interactions
TNFAIP3 has been shown to interact with TNIP1, TRAF1, TRAF2, IKBKG, TAX1BP1, YWHAB, YWHAZ, TRAF6 and YWHAH.
Association with rheumatoid arthritis
The TNFAIP3 locus is implicated as a positively associated factor in rheumatoid arthritis (RA). The rs5029937 (T) and the rs6920220 (A) SNPs increase risk of RA by 20 to 40% respectively. A third SNP, rs10499194 (T) is found less often in rheumatoid arthritis but this negative association may not be statistically meaningful.
Other diseases
An association with infantile onset intractable infl |
https://en.wikipedia.org/wiki/WFS1 | Wolframin is a protein that in humans is encoded by the WFS1 gene.
Function
This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Wolframin appears to function as a cation-selective ion channel.
Clinical significance
Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease is characterized by non-immune insulin-dependent diabetes mellitus and bilateral progressive optic atrophy, usually presenting in childhood or early adult life. Diverse neurologic symptoms, including a predisposition to psychiatric illness, may also be associated with this disorder. A large number and variety of mutations in this gene, particularly in exon 8, can be associated with this syndrome. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38.
Mutations in this gene have also been associated with congenital cataracts.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on WFS1-Related Disorders |
https://en.wikipedia.org/wiki/PAX8 | Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.
Function
This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins which contain a paired box domain, an octapeptide, and a paired-type homeodomain. The PAX gene family has an important role in the formation of tissues and organs during embryonic development and maintaining the normal function of some cells after birth. The PAX genes give instructions for making proteins that attach themselves to certain areas of DNA. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. PAX8 releases the hormones important for regulating growth, brain development, and metabolism. Also functions in very early stages of kidney organogenesis, the müllerian system, and the thymus. Additionally, PAX8 is expressed in the renal excretory system, epithelial cells of the endocervix, endometrium, ovary, Fallopian tube, seminal vesicle, epididymis, pancreatic islet cells and lymphoid cells. PAX8 and other transcription factors play a role in binding to DNA and regulating the genes that drive thyroid hormone synthesis (Tg, TPO, Slc5a5 and Tshr).
PAX8 (and PAX2) is one of the important regulators of urogenital system morphogenesis. They play a role in the specification of the first renal cells of the embryo and remain essential players throughout development.
PAX8 has |
https://en.wikipedia.org/wiki/PDCD6IP | Programmed cell death 6-interacting protein also known as ALIX is a protein that in humans is encoded by the PDCD6IP gene.
This gene encodes a protein thought to participate in programmed cell death. Studies using mouse cells have shown that overexpression of this protein can block apoptosis. In addition, the product of this gene binds to the product of the PDCD6 gene, a protein required for apoptosis, in a calcium-dependent manner. This gene product also binds to endophilins, proteins that regulate membrane shape during endocytosis. Overexpression of this gene product and endophilins results in cytoplasmic vacuolization which may be partly responsible for the protection against cell death.
Function
PDCD6IP protein is part of ESCRT pathway. It participates in the membrane scission of the revers topology budding and participates in multivesicular body formation. It is also vital at the later stages and for successful completion of cytokinesis.
Interactions
PDCD6IP has been shown to interact with PDCD6. The V domain of PDCD6IP recognises Short linear motif LYPxLxxL and this motif is mimicked by p6 late domain of HIV and related viruses which facilitates viral hijacking of ESCRT pathway and consequential budding of viral particles.
References
Further reading
External links |
https://en.wikipedia.org/wiki/GNE%20%28gene%29 | Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is an enzyme that in humans is encoded by the GNE gene.
The bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase/N-acetylmannosamine kinase) regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. UDP-GlcNAc 2-epimerase activity is rate-limiting for the biosynthesis of sialic acid and is required for sialylation in hematopoietic cells. The activity of the enzyme can be controlled at the transcriptional level and can affect the sialylation and function of specific cell surface molecules expressed on B cells and myeloid cells. Modification of cell surface molecules with sialic acid is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free NeuAc.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Sialuria |
https://en.wikipedia.org/wiki/PSME3 | Proteasome activator complex subunit 3 is a protein that in humans is encoded by the PSME3 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the gamma subunit of the 11S regulator. Six gamma subunits combine to form a homohexameric ring. Two transcript variants encoding different isoforms have been identified.
Interactions
PSME3 has been shown to interact with P53 and Mdm2.
References
Further reading
External links |
https://en.wikipedia.org/wiki/PYCARD | PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome.
NMR structure of full-length ASC: PDB ID 2KN6
Function
This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery.
PYCARD can occur in four different isoforms. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with nucleotide oligomerization domain-like receptors (NLRs) and caspase-1. Unlike isoform 1, isoform 2 is involved in direct IL-1β processing regulation. Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to |
https://en.wikipedia.org/wiki/ATP2B4 | Plasma membrane calcium-transporting ATPase 4 is an enzyme that in humans is encoded by the ATP2B4 gene.
The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified.
Interactions
ATP2B4 has been shown to interact with CASK.
References
Further reading
External links |
https://en.wikipedia.org/wiki/DDR1 | Discoidin domain receptor family, member 1, also known as DDR1 or CD167a (cluster of differentiation 167a), is a human gene.
Function
Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene is a RTK that is widely expressed in normal and transformed epithelial cells and is activated by various types of collagen. This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the Dictyostelium discoideum protein discoidin I in their extracellular domain. Its autophosphorylation is achieved by all collagens so far tested (type I to type VI). A closely related family member is the DDR2 protein. In situ studies and Northern-blot analysis showed that expression of this encoded protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, this protein is significantly over-expressed in several human tumors from breast, ovarian, esophageal, and pediatric brain. This gene is located on chromosome 6p21.3 in proximity to several HLA class I genes. Alternative splicing of this gene results in multiple transcript variants.
References
Further reading
Clusters of differentiation
Tyrosine kinase receptors |
https://en.wikipedia.org/wiki/Tripeptidyl%20peptidase%20I | Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the TPP1 gene. TPP1 should not be confused with the TPP1 shelterin protein which protects telomeres and is encoded by the ACD gene. Mutations in the TPP1 gene leads to late infantile neuronal ceroid lipofuscinosis.
Structure
Gene
The human gene TPP1 encodes a member of the sedolisin family of serine proteases. The human gene has 13 exons and locates at the chromosome band 11p15.
Protein
The human TPP1 is 61kDa in size and composed of 563 amino acids. An isoform of 34.5kDa and 320 amino acids is generated by alternative splicing and a peptide fragment of 1-243 amino acid is missing. TPP1 contains a globular structure with a subtilisin-like fold, a Ser475-Glu272-Asp360 catalytic triad. It also contains an octahedrally coordinated Ca2+-binding site that are characteristic features of the S53 sedolisin family of peptidases. Unlike other S53 peptidases, it has steric constraints on the P4 substrate pocket, which might contribute to its preferential cleavage of tripeptides from the unsubstituted N-terminus of proteins. Two alternative conformations of the catalytic Asp276 are associated with the activation status of TPP1.
Function
High expression of TPP1 is found in bone marrow, placenta, lung, pineal and lymphocytes. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates and has weaker endopeptidase activity. It is syn |
https://en.wikipedia.org/wiki/CUTL1 | Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.
Function
The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It regulates gene expression, morphogenesis, and differentiation and it also plays a role in cell cycle progression, particularly at S-phase. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined, and the p200 isoform of Cux1 is processed proteolytically to smaller active isoforms, such as p110. Cux1 DNA binding is stimulated by activation of the PAR2/F2RL1 cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulate Matrix metalloproteinase 10, Interleukin1-alpha, and Cyclo-oxygenase 2 (COX2) genes.
Role in tumor growth
Genetic data from over 7,600 cancer patients shows that over 1% has the deactivated CUX1 which links to progression of tumor growth. Researchers from the Wellcome Trust Sanger Institute reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor, PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other known gene mutations that cause cancer, this deactivated gene is found across many cancer t |
https://en.wikipedia.org/wiki/HNRNPC | Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.
It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these ART.
Function
This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing(reference: Koenig J. nature structural and Molecular Biology 2010: iCLIP) and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. Transcriptional regulation by hormonal 1,25-dihydroxyvitamin D(3) (calcitriol) involves occupancy of vitamin D response elements (VDREs) by HNRNPC or 1,25(OH)(2)D(3)-bound vitamin D receptor (VDR). This relationship is disrupted by elevated HNRNPC, causing a form of hereditary vitamin D-resistant rickets (HVDRR) in both humans and non-human primates. The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Species-specific tetramerization of HNRNPC subunits is important to its nucleic acid binding, whereby over-expression of major human HNRNPC subunits in mouse osteoblastic ce |
https://en.wikipedia.org/wiki/KCNA5 | Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or Kv1.5, is a protein that in humans is encoded by the KCNA5 gene.
Function
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. KCNA5 encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, the function of which could restore the resting membrane potential of beta cells after depolarization, thereby contributing to the regulation of insulin secretion. This gene is intronless, and the gene is clustered with genes KCNA1 and KCNA6 on chromosome 12. Mutations in this gene have been related to both atrial fibrillation and sudden cardiac death. KCNA5 are also key players in pulmonary vascular function, where they play a role in setting the resting membrane potential and its involvement during hypoxic pulmonary vasoconstriction.
Interactions
KCNA5 has been shown to interact with DLG4, PDZ domain-containing proteins such as SAP97, and Actinin, alpha 2.
See also
Voltage-gated potassium channel
References
Further reading
External links
Ion channels |
https://en.wikipedia.org/wiki/Laminin%2C%20alpha%203 | Laminin subunit alpha-3 is a protein that in humans is encoded by the LAMA3 gene.
Function
Laminins are basement membrane components thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. The protein encoded by this gene is the alpha-3 chain of laminin 5, which is a complex glycoprotein composed of three subunits (alpha, beta, and gamma). Alternatively spliced transcript variants encoding different isoforms have been identified.
Laminin 5 is thought to be involved in cell adhesion, signal transduction and differentiation of keratinocytes.
Clinical significance
Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa.
It may be associated with Laryngoonychocutaneous syndrome.
Interactions
Laminin, alpha 3 has been shown to interact with SDC2.
References
Further reading
Laminins |
https://en.wikipedia.org/wiki/Thrombopoietin%20receptor | The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 (Cluster of Differentiation 110) is a protein that in humans is encoded by the MPL (myeloproliferative leukemia virus) oncogene.
Discovery
In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation.
Function
The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation.
The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin, CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.
Interactions
Myeloproliferative leukemia virus oncogene |
https://en.wikipedia.org/wiki/PITX2 | Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.
Function
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. This protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein is involved in the development of the eye, tooth, and abdominal organs. This protein acts as a transcriptional regulator involved in the basal and hormone-regulated activity of prolactin. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Three transcript variants encoding distinct isoforms have been identified for this gene.
Pitx2 is responsible for the establishment of the left-right axis, the asymmetrical development of the heart, lungs, and spleen, twisting of the gut and stomach, as well as the development of the eyes. Once activated Pitx2 will be locally expressed in the left lateral mesoderm, tubular heart, and early gut which leads to the asymmetrical development of organs and looping of the gut. When Pitx2 is deleted, the irregular morphogenesis of organs results on the left hand side. Pitx2 is left-laterally expressed controlling the morphology of the left visceral organs. Expression of Pitx2 is controlled by an intronic enhancer ASE and Nodal. It appears that while Nodal controls cranial expression of Pitx2, ASE controls |
https://en.wikipedia.org/wiki/PSMA2 | Proteasome subunit alpha type-2 is a protein that in humans is encoded by the PSMA2 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
Structure
Protein expression
The gene PSMA2 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. Using FISH, the human gene HC3 (old nomenclature for PMSA2, 4.3kb with 3 exons) was mapped at chromosome band 6q27. The human protein proteasome subunit alpha type-2 is also known as 20S proteasome subunit alpha-2 (based on systematic nomenclature). The protein is 25.9 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.77.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.
Function
Crystal structures of isolated 20S proteasome c |
https://en.wikipedia.org/wiki/PSMC4 | 26S protease regulatory subunit 6B, also known as 26S proteasome AAA-ATPase subunit Rpt3, is an enzyme that in humans is encoded by the PSMC4 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex Six 26S proteasome AAA-ATPase subunits (Rpt1, Rpt2, Rpt3 (this protein), Rpt4, Rpt5, and Rpt6) together with four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13) form the base sub complex of 19S regulatory particle for proteasome complex.
Gene
The gene PSMC4 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit has been shown to interact with an orphan member of the nuclear hormone receptor superfamily highly expressed in liver, and with gankyrin, a liver oncoprotein. Two transcript variants encoding different isoforms have been identified. The human PSMC3 gene has 11 exons and locates at chromosome band 19q13.11-q13.13.
Protein
The human protein 26S protease regulatory subunit 6B is 47kDa in size and composed of 418 amino acids. The calculated theoretical pI of this protein is 5.09.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolyt |
https://en.wikipedia.org/wiki/PSMD7 | 26S proteasome non-ATPase regulatory subunit 7, also known as 26S proteasome non-ATPase subunit Rpn8, is an enzyme that in humans is encoded by the PSMD7 gene.
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.
Gene
The gene PSMD7 encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. The human gene PSMD7 has 7 Exons and locates at chromosome band 16q22.3.
Protein
The human protein 26S proteasome non-ATPase regulatory subunit 14 is 37 kDa in size and composed of 324 amino acids. The calculated theoretical pI of this protein is 6.11.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-sh |
https://en.wikipedia.org/wiki/PTPRF | Receptor-type tyrosine-protein phosphatase F is an enzyme that, in humans, is encoded by the PTPRF gene.
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig-like domains similar to those of the neural cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherens junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.
Interactions
PTPRF has been shown to interact with Beta-catenin and liprin-alpha-1.
References
Further reading |
https://en.wikipedia.org/wiki/RAC2 | Rac2 (Ras-related C3 botulinum toxin substrate 2) is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.
Members of Rho family of GTPases appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.
Interactions
Rac2 has been shown to interact with ARHGDIA and Nitric oxide synthase 2A.
See also
NADPH oxidase
References
Further reading
External links
RAC2 Info with links in the Cell Migration Gateway |
https://en.wikipedia.org/wiki/RALA | Ras-related protein Ral-A (RalA) is a protein that in humans is encoded by the RALA gene on chromosome 7. This protein is one of two paralogs of the Ral protein, the other being RalB, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.
Structure
The Ral isoforms share an 80% overall match in amino acid sequence and 100% match in their effector-binding region. The two isoforms mainly differ in the C-terminal hypervariable region, which contains multiple sites for post-translational modification, leading to diverging subcellular localization and biological function. For example, phosphorylation of Serine 194 on RalA by the kinase Aurora A results in the relocation of RalA to the inner mitochondrial membrane, where RalA helps carry out mitochondrial fission; whereas phosphorylation of Serine 198 on RalB by the kinase PKC results in the relocation of RalB to other internal membranes and activation of its tumorigenic function.
Function
RalA is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. As a Ras GTPase, RalA functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. RalA can be activated by RalGEFs and, in turn, activate effectors in signal transduction pathways leading to biological outcomes. |
https://en.wikipedia.org/wiki/S100A10 | S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the S100A10 gene in humans and the S100a10 gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells. They regulate a number of cellular processes such as cell cycle progression and differentiation. The S100 protein is implicated in exocytosis and endocytosis by reorganization of F-actin.
The p11 protein is linked with the transport of neurotransmitters. Found in the brain of humans and other mammals, it has been implicated in the regulation of mood. In addition, due to its interaction with serotonin-signaling proteins and its correlation with symptoms of mood disorders, p11 is a new potential target for drug therapy.
Gene
The S100 gene family, localized in the cytoplasm and nucleus of cells, includes at least 13 members that are located as a cluster on chromosome 1q21. In humans, 19 family members are
currently known, with most S100 genes (S100A1 to S100A16). Proteins in the S100 gene family are known to regulate a number of cellular processes, such as cell cycle progression and differentiation.
Structure
The p11 protein can be found as a free monomer, a homodimer, or a heterotetramer composed of a p11 dimer complex with two molecules of annexin II. The homodimer or heterotetramer can, in turn, dimerize through formation of two di |
https://en.wikipedia.org/wiki/SCNN1A | The SCNN1A gene encodes for the α subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by SCNN1B, SCNN1G, and SCNN1D.
ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation of action potentials in neurons. The abbreviation for the genes encoding for voltage-gated sodium channel starts with three letters: SCN. In contrast to these sodium channels, ENaC is constitutively active and is not voltage-dependent. The second N in the abbreviation (SCNN1A) represents that these are NON-voltage-gated channels.
In most vertebrates, sodium ions are the major determinant of the osmolarity of the extracellular fluid. ENaC allows transfer of sodium ions across the epithelial cell membrane in so-called "tight-epithelia" that have low permeability. The flow of sodium ions across epithelia affects osmolarity of the extracellular fluid. Thus, ENaC plays a central role in the regulation of body fluid and electrolyte homeostasis and consequently affects blood pressure.
As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel".
History
The first mRNA encoding the alpha subunit of ENaC was isolated by two independent groups by screening a rat colon cDNA library.
Gene structure
The human gene SCNN1A is located in the short a |
https://en.wikipedia.org/wiki/Excitatory%20amino%20acid%20transporter%202 | Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the SLC1A2 gene. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.
Function
SLC1A2 / EAAT2 is a member of a family of the solute carrier family of proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. EAAT2 is responsible for over 90% of glutamate reuptake within the brain.
Clinical significance
Mutations in and decreased expression of this protein are associated with amyotrophic lateral sclerosis (ALS). The drug riluzole approved for the treatment of ALS upregulates EAAT2.
Ceftriaxone, an antibiotic, has been shown to induce/enhance the expression of EAAT2, resulting in reduced glutamate activity. Ceftriaxone has been shown to reduce the development and expression of tolerance to opiates and other drugs of abuse. EAAT2 may possess an important role in drug addiction and tolerance to addictive drugs.
Upregulation of EAAT2 (GLT-1) causes impairment of prepulse inhibition, a sensory gating deficit present in schizophrenics and schizophrenia animal mo |
https://en.wikipedia.org/wiki/SNRPB | Small nuclear ribonucleoprotein-associated proteins B and B' is a protein that in humans is encoded by the SNRPB gene.
Function
The protein encoded by this gene is one of several nuclear proteins that are found in common among U1, U2, U4/U6, and U5 small ribonucleoprotein particles (snRNPs). These snRNPs are involved in pre-mRNA splicing, and the encoded protein may also play a role in pre-mRNA splicing or snRNP structure. Autoantibodies from patients with systemic lupus erythematosus frequently recognize epitopes on the encoded protein. Two transcript variants encoding different isoforms (B and B') have been found for this gene.
Interactions
SNRPB has been shown to interact with DDX20 and Coilin.
References
Further reading |
https://en.wikipedia.org/wiki/Bestrophin%201 | Bestrophin-1 (Best1) is a protein that, in humans, is encoded by the BEST1 gene (RPD ID - 5T5N/4RDQ).
The bestrophin family of proteins comprises four evolutionary related genes (BEST1, BEST2, BEST3, and BEST4) that code for integral membrane proteins. This family was first identified in humans by linking a BEST1 mutation with Best vitelliform macular dystrophy (BVMD). Mutations in the BEST1 gene have been identified as the primary cause for at least five different degenerative retinal diseases.
The bestrophins are an ancient family of structurally conserved proteins that have been identified in nearly every organism studied from bacteria to humans. In humans, they function as calcium-activated anion channels, each of which has a unique tissue distribution throughout the body. Specifically, the BEST1 gene on chromosome 11q13 encodes the Bestrophin-1 protein in humans whose expression is highest in the retina.
Structure
Gene
The bestrophin genes share a conserved gene structure, with almost identical sizes of the 8 RFP-TM domain-encoding exons and highly conserved exon-intron boundaries. Each of the four bestrophin genes has a unique 3-prime end of variable length.
BEST1 has been shown by two independent studies to be regulated by Microphthalmia-associated transcription factor.
Protein
Bestrophin-1 is an integral membrane protein found primarily in the retinal pigment epithelium (RPE) of the eye. Within the RPE layer, it is mainly located on the basolateral plasma m |
https://en.wikipedia.org/wiki/Optineurin | Optineurin is a protein that in humans is encoded by the OPTN gene.
Function
This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.
Model organisms
Model organisms have been used in the study of OPTN function. A conditional knockout mouse line, called Optntm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program – a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists – at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty one tests were carried out on mutant mice, however no significant abnormalities were observed.
Interactions
Optineurin has been shown to interact with Huntingtin and RAB8A.
References
Fur |
https://en.wikipedia.org/wiki/F11%20receptor | Junctional adhesion molecule A is a protein that in humans is encoded by the F11R gene. It has also been designated as CD321 (cluster of differentiation 321).
Function
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is an important regulator of tight junction assembly in epithelia. In addition, the encoded protein can act as (1) a receptor for reovirus, (2) a ligand for the integrin LFA1, involved in leukocyte transmigration, and (3) a platelet receptor. Multiple transcript variants encoding two different isoforms have been found for this gene.
Interactions
F11 receptor has been shown to interact with MLLT4, CASK and Tight junction protein 1.
References
Further reading
External links
Clusters of differentiation |
https://en.wikipedia.org/wiki/Signal-regulatory%20protein%20alpha | Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
SIRPα acts as inhibitory receptor and interacts with a broadly expressed transmembrane protein CD47 also called the "don't eat me" signal. This interaction negatively controls effector function of innate immune cells such as host cell phagocytosis. SIRPα diffuses laterally on the macrophage membrane and accumulates at a phagocytic synapse to bind CD47 and signal 'self', which inhibits the cytoskeleton-intensive process of phagocytosis by the macrophage. This is analogous to the self signals provided by MHC class I molecules to NK cells via Ig-like or Ly49 receptors. NB. Protein shown to the right is CD47 not SIRP α.
Structure
The cytoplasmic region of SIRPα is highly conserved between rats, mice and humans. Cytoplasmic region contains a number of tyrosine residues, which likely act as ITIMs. Upon CD47 ligation, SIRPα is phosphorylated and recruits phosphatases like SHP1 and SHP2. The extracellular region contains three Immunoglobulin superfamily domains – single V-set and two C1-set IgSF domains. SIRP β and γ have the similar extracellular structure but different cytoplasmic regions giving contrasting types of signals. SIRP α polymorphisms are found in ligand-binding IgSF V-set domain but it does not affect ligand binding. One idea is that the polymorphism is important to protect the receptor of pathogens binding.
|
https://en.wikipedia.org/wiki/AXL%20receptor%20tyrosine%20kinase | Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene. The gene was initially designated as UFO, in allusion to the unidentified function of this protein. However, in the years since its discovery, research into AXL's expression profile and mechanism has made it an increasingly attractive target, especially for cancer therapeutics. In recent years, AXL has emerged as a key facilitator of immune escape and drug-resistance by cancer cells, leading to aggressive and metastatic cancers.
AXL is a cell surface receptor tyrosine kinase, part of the TAM family of kinases including TYRO3 and MERTK.
Gene and protein structure
The Axl gene is evolutionarily conserved between vertebrate species. This gene has two different alternatively spliced transcript variants.
The protein encoded by this gene is a member of the receptor tyrosine kinase subfamily. Although it is similar to other receptor tyrosine kinases, the Axl protein represents a unique structure of the extracellular region that juxtaposes IgL and FNIII repeats.
The AXL protein is characterized by an extracellular structure consisting of two fibronectin type 3-like repeats and two immunoglobulin-like repeats along with its intracellular tyrosine kinase domain.
AXL is in close vicinity to the BCL3 oncogene, which is at 19q13.1-q13.2.
Function
The AXL receptor transduces signals from the extracellular matrix into the cytoplasm by binding growth factors like vitamin K-dependent protein g |
https://en.wikipedia.org/wiki/BCL2-related%20protein%20A1 | Bcl-2-related protein A1 is a protein in humans which is encoded by the BCL2A1 gene.
Function
This gene encodes a member of the bcl2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis, and tumorigenesis. The protein encoded by this gene can reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators and is up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester, and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival.
In melanocytic cells BCL2A1 gene expression may be regulated by MITF.
Interactions
BCL2-related protein A1 has been shown to interact with:
Bcl-2-associated X protein, and
Bcl-2-associated death promoter.
References
External links
Further reading |
https://en.wikipedia.org/wiki/CDH3%20%28gene%29 | Cadherin-3, also known as P-Cadherin, is a protein that in humans is encoded by the CDH3 gene.
Function
This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas.
Clinical significance
Mutations in this gene have been associated with congenital hypotrichosis with juvenile macular dystrophy.
Interactions
CDH3 (gene) has been shown to interact with:
Beta-catenin,
CDH1,
Catenin (cadherin-associated protein), alpha 1,
Nephrin and
Plakoglobin.
History
Cadherin-3 was first described in 1986 by Masatoshi Takeichi's laboratory as a new cadherin molecule most abundant in the developing mouse placenta – hence "P-cadherin".
See also
EEM syndrome
References
Further reading
External links |
https://en.wikipedia.org/wiki/Cystatin%20A | Cystatin-A is a protein that in humans is encoded by the CSTA gene.
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins, and kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer.
Interactions
Cystatin A has been shown to interact with Cathepsin B and CTSL1.
See also
Peptide Transporter Carbon Starvation (cstA) Family
References
Further reading
External links
Cystatin: a protein that flips out! QUite Interesting PDB Structure article at PDBe
The MEROPS online database for peptidases and their inhibitors: I25.001 |
https://en.wikipedia.org/wiki/DYRK1A | Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.
Function
DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene.
Dyrk1a has also been shown to modulate plasma homocysteine level in a mouse model of overexpression.
Clinical significance
DYRK1A is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. In addition, a polymorphism (SNP) in DYRK1A was found to be associated with HIV-1 replication in monocyte-derived macrophages, as well as with slower progression to AIDS in two independent cohorts of HIV-1-infected individuals. Mutations in DYRK1A are also associated with autism spectrum disorder.
Interactions
DYRK1A has been |
https://en.wikipedia.org/wiki/ERCC5 | DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.
Function
Excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G) is involved in excision repair of UV-induced DNA damage. Mutations cause Cockayne syndrome, which is characterized by severe growth defects, mental retardation, and cachexia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been described, but the biological validity of all variants has not been determined.
Mutations in ERCC5 cause arthrogryposis.
XPG is a structure specific endonuclease that incises DNA at the 3’ side of the damaged nucleotide during nucleotide excision repair.
Syndromes
Mutational defects in the Ercc5(Xpg) gene can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or in combination with the severe neurodevelopmental disorder Cockayne syndrome (CS) or the infantile lethal cerebro-oculo-facio-skeletal syndrome.
Mouse model
An Ercc5(Xpg) mutant mouse model presented features of premature aging including cachexia and osteoporosis with pronounced degenerative phenotypes in both liver and brain. These mutant mice developed a multi-system premature aging degenerative phenotype that appears to strengthen the link between DNA damage and aging. (see DNA damage theory of aging).
Dietary restriction, which extends lifespan of wild-type mice, also substantially |
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