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https://en.wikipedia.org/wiki/Tinkering%20with%20Trouble | Tinkering with Trouble is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd - Lonesome Luke aka Easy Otis
Snub Pollard - (as Harry Pollard)
Gene Marsh
Bebe Daniels
See also
Harold Lloyd filmography
External links
1915 films
American silent short films
1915 comedy films
1915 short films
American black-and-white films
Films directed by Hal Roach
Lonesome Luke films
American comedy short films
1910s American films
Silent American comedy films |
https://en.wikipedia.org/wiki/Great%20While%20It%20Lasted | Great While It Lasted is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Gene Marsh
Clifford Silsby
Snub Pollard
Bebe Daniels
Arthur Harrison
See also
Harold Lloyd filmography
External links
1915 films
1915 short films
American silent short films
1915 comedy films
American black-and-white films
Films directed by Hal Roach
Silent American comedy films
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Ragtime%20Snap%20Shots | Ragtime Snap Shots is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Snub Pollard (as Harry Pollard)
Earl Mohan
Gene Marsh
Bebe Daniels
See also
Harold Lloyd filmography
External links
1915 films
American silent short films
1915 comedy films
1915 short films
American black-and-white films
Films directed by Hal Roach
Silent American comedy films
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Webtag | Webtag is an on-line bioinformatics tool providing oligonucleotide sequences (usually called tags or anchors) that are absent from a specified genome. These tags can be appended to gene specific primers for reverse transcriptase polymerase chain reaction (RT-PCR) experiments, circumventing genomic DNA contamination.
Background
RT-PCR is a technique used for the detection of even very low copy mRNA transcripts. The sensitivity of the technique also makes it susceptible to DNA contamination. Since PCR is unable to distinguish between cDNA targets and genomic DNA contamination, false positives and/or erroneous quantitative results are possible.
In order to overcome genomic DNA contamination in transcriptional studies, reverse template-specific polymerase chain reaction, a modification of RT-PCR is used. The possibility of using tags whose sequences are not found in the genome further improves reverse specific polymerase chain reaction experiments. The use of anchors, or tags, in the 5' region of a gene specific primer or poly-T tail allows for RNA-specific amplification, and constitutes a viable strategy. Techniques such as RS-PCR and (EXACT) RT-PCR are based on the integration of such tags (unique sequences not present in genomic DNA) in the 5' end of the first strand cDNA, permitting RNA-specific amplification without loss of sensitivity.
Webtag
This web based service builds on the Tagenerator tool, but is very fast because all tags are pre-generated and stored in a databas |
https://en.wikipedia.org/wiki/A%20Foozle%20at%20the%20Tee%20Party | A Foozle at the Tee Party is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Snub Pollard (as Harry Pollard)
Earl Mohan
Gene Marsh
Bebe Daniels
Arthur Harrison
Clifford Silsby
See also
List of American films of 1915
Harold Lloyd filmography
References
External links
1915 films
Silent American comedy films
1915 short films
American silent short films
1915 comedy films
American black-and-white films
Films directed by Hal Roach
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Ruses%2C%20Rhymes%20and%20Roughnecks | Ruses, Rhymes and Roughnecks is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Snub Pollard (as Harry Pollard)
Gene Marsh
Bebe Daniels
Jack Spinks
See also
Harold Lloyd filmography
External links
1915 films
American silent short films
1915 comedy films
American black-and-white films
Films directed by Hal Roach
1915 short films
Silent American comedy films
Lonesome Luke films
American comedy short films
1910s American films
1910s English-language films |
https://en.wikipedia.org/wiki/Lonesome%20Luke%2C%20Social%20Gangster | Lonesome Luke, Social Gangster is a 1915 American short comedy film featuring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Snub Pollard (as Harry Pollard)
Gene Marsh
Bebe Daniels
See also
Harold Lloyd filmography
References
External links
1915 films
1915 short films
American silent short films
1915 comedy films
American black-and-white films
Films directed by Hal Roach
Films directed by J. Farrell MacDonald
Silent American comedy films
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Oracle%20Developer%20Studio | Oracle Developer Studio, formerly named Oracle Solaris Studio, Sun Studio, Sun WorkShop, Forte Developer, and SunPro Compilers, is the Oracle Corporation's flagship software development product for the Solaris and Linux operating systems. It includes optimizing C, C++, and Fortran compilers, libraries, and performance analysis and debugging tools, for Solaris on SPARC and x86 platforms, and Linux on x86/x64 platforms, including multi-core systems.
Oracle Developer Studio is downloadable and usable at no charge; however, there are many security and functionality patch updates which are only available with a support contract from Oracle.
Version 12.4 added partial support for the C++11 language standard. All C++11 features are supported except for concurrency and atomic operations, and user-defined literals. Version 12.6 supports the C++14 language standard.
Languages
C
C++
Fortran
Supported architectures
SPARC
i86pc (x86 and x86-64)
Components
The Oracle Developer software suite includes:
C, C++, and Fortran compilers and support libraries
dbx and frontends
lint
A NetBeans-based IDE
Performance Analyzer
Thread analyzer
Sun performance library
Distributed make
Compiler optimizations
A common optimizing backend is used for code generation.
A high-level intermediate representation called Sun IR is used, and high-level optimizations done in the iropt (intermediate representation optimizer) component are operated at the Sun IR level. Major optimizations include: |
https://en.wikipedia.org/wiki/Luke%20Lugs%20Luggage | Luke Lugs Luggage is a 1916 American short comedy film starring Harold Lloyd.
Cast
Harold Lloyd as Lonesome Luke
Gene Marsh
Snub Pollard
Bebe Daniels
See also
Harold Lloyd filmography
References
External links
1916 films
1916 comedy films
Silent American comedy films
American black-and-white films
Films directed by Hal Roach
1916 short films
American silent short films
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Lonesome%20Luke%20Lolls%20in%20Luxury | Lonesome Luke Lolls in Luxury is a 1916 American short comedy film featuring Harold Lloyd. It was a silent film.
Cast
Harold Lloyd - Lonesome Luke
Gene Marsh
Snub Pollard
Bebe Daniels
See also
Harold Lloyd filmography
References
External links
1916 films
1916 comedy films
Silent American comedy films
American black-and-white films
1916 short films
American silent short films
Films directed by Hal Roach
Lonesome Luke films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/Luke%2C%20the%20Candy%20Cut-Up | Luke, the Candy Cut-Up is a 1916 American short comedy film starring Harold Lloyd. A print of the film survives in George Eastman House.
Cast
Harold Lloyd - Lonesome Luke
Snub Pollard
Gene Marsh
Bebe Daniels
Sammy Brooks
Billy Fay
Fred C. Newmeyer
Charles Stevenson
See also
Harold Lloyd filmography
References
External links
1916 films
1916 comedy films
Silent American comedy films
American black-and-white films
Films directed by Hal Roach
Lonesome Luke films
1916 short films
American silent short films
American comedy short films
1910s American films |
https://en.wikipedia.org/wiki/U-quadratic%20distribution | In probability theory and statistics, the U-quadratic distribution is a continuous probability distribution defined by a unique convex quadratic function with lower limit a and upper limit b.
Parameter relations
This distribution has effectively only two parameters a, b, as the other two are explicit functions of the support defined by the former two parameters:
(gravitational balance center, offset), and
(vertical scale).
Related distributions
One can introduce a vertically inverted ()-quadratic distribution in analogous fashion.
Applications
This distribution is a useful model for symmetric bimodal processes. Other continuous distributions allow more flexibility, in terms of relaxing the symmetry and the quadratic shape of the density function, which are enforced in the U-quadratic distribution – e.g., beta distribution and gamma distribution.
Moment generating function
Characteristic function
Beamforming
The quadratic U and inverted quadratic U distribution has an application to beamforming and pattern synthesis.
References
Continuous distributions |
https://en.wikipedia.org/wiki/Occupational%20Employment%20and%20Wage%20Statistics | The Occupational Employment and Wage Statistics) (OEWS) survey is a semi-annual survey of approximately 200,000 non-farm business establishments conducted by the Bureau of Labor Statistics (BLS), headquartered in Washington, DC with six regional offices and one office in each state. Until the spring of 2021 it was officially called the Occupational Employment Statistics (OES), and it is often cited or documented with that name or abbreviation.
Purpose
The OEWS survey is designed to produce estimates of employment and wages by occupation by four-digit North American Industry Classification System (NAICS) in each State-level Metropolitan Statistical Area (MSA-“urban”) or Balance-of-State (BOS-“rural”) geographic level, and their aggregates. Semi-annually, a "current" sample is combined with the immediate five prior samples to produce a “combined” sample of approximately 1.2 million establishments (6 x 200,000) to produce OES Estimates.
Process
During the sampling process, the National frame (using data collected by the Quarterly Census of Employment and Wages) of business establishments (approximately 7 million frame business establishments in-scope) is allocated for 1.2 million sample cases, then “divided” by 6 for each geography/industry cell (1.2 million/6=200,000).
After the sample of 200,000 is selected, data from each selected business establishment are collected by each state over the next nine months and reported back to BLS. These data include employment counts |
https://en.wikipedia.org/wiki/William%20Shockley%20%28disambiguation%29 | William Shockley (1910–1989) was a British-born American physicist and Nobel Prize winner for co-inventing the transistor.
William Shockley may also refer to:
Bill Shockley (1937–1992), American footballer
William R. Shockley (1918–1945), Medal of Honor recipient
William Shockley (actor) (born 1963), American actor and musician
William Hillman Shockley, American mining engineer and plant collector, father of William Bradford Shockley |
https://en.wikipedia.org/wiki/Phase%20%28video%20game%29 | Phase is a music-themed iPod game created by Harmonix exclusively for the iPod click wheel interface. It is similar to other Harmonix games Amplitude and FreQuency.
Gameplay
Phase is played in a forced single-point perspective view of a three line track. Down each line come colored circles, and the player must click the corresponding button on the click wheel when the circle reaches the bottom of the screen. The circles are arranged on the track in relation to the beat of the music track being played.
Additionally, there are occasional series of smaller, more closely spaced dots that will sweep across the track. These require the player to swipe their finger across the click wheel at the correct pace, instead of clicking the wheel buttons.
The game comes with Easy, Medium, and Hard settings available for immediate play. After completing a marathon with the Hard difficulty setting, Expert mode is made available. In the same way, completing a marathon on Expert unlocks Insane mode. The difficulty settings control the speed of the track and the number of the dots, as well as their value.
Soundtrack
Phase ships with seven songs, some by bands of Harmonix employees, but can be made to work with any song on the iPod as long as it is longer than 30 seconds but less than 30 minutes long. Custom songs must be added to a Phase playlist in iTunes, where they are processed for proper interpretation and become available in the game. The Phase music playlist is limited to 1,000 song |
https://en.wikipedia.org/wiki/Carbonic%20anhydrase%20II | Carbonic anhydrase II (gene name CA2), is one of sixteen forms of human α carbonic anhydrases. Carbonic anhydrase catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis.
Renal carbonic anhydrase allows the reabsorption of bicarbonate ions in the proximal tubule.
Loss of carbonic anhydrase activity in bones impairs the ability of osteoclasts to promote bone resorption, leading to osteopetrosis.
Interactions
Carbonic anhydrase II has been shown to interact with band 3 and sodium-hydrogen antiporter 1.
References
Further reading |
https://en.wikipedia.org/wiki/ERBB3 | Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound protein that in humans is encoded by the ERBB3 gene.
ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. The kinase-impaired ErbB3 is known to form active heterodimers with other members of the ErbB family, most notably the ligand binding-impaired ErbB2.
Gene and expression
The human ERBB3 gene is located on the long arm of chromosome 12 (12q13). It is encoded by 23,651 base pairs and translates into 1342 amino acids.
During human development, ERBB3 is expressed in skin, bone, muscle, nervous system, heart, lungs, and intestinal epithelium. ERBB3 is expressed in normal adult human gastrointestinal tract, reproductive system, skin, nervous system, urinary tract, and endocrine system.
Structure
ErbB3, like the other members of the ErbB receptor tyrosine kinase family, consists of an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain contains four subdomains (I-IV). Subdomains I and III are leucine-rich and are primarily involved in ligand binding. Subdomains II and IV are cysteine-rich and most likely contribute to protein conformation and stability through the formation of disulfide bonds. Subdomain II also contains the dimerization loop required for dimer formation. The cytoplasmic domain contains a juxtamembrane segment, a kinase domain, and a |
https://en.wikipedia.org/wiki/Interleukin-12%20subunit%20beta | Subunit beta of interleukin 12 (also known as IL-12B, natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor p40, or interleukin-12 subunit p40) is a protein subunit that in humans is encoded by the IL12B gene. IL-12B is a common subunit of interleukin 12 and interleukin 23.
Function
This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kDa cytokine receptor like subunit encoded by this gene, and a 35 kDa subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children.
Role as IL-23 subunit
Interleukin-12 p40 also serves as a subunit of interleukin 23.
References
Further reading
Human proteins
Interleukins |
https://en.wikipedia.org/wiki/STX1A | Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.
Function
Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization of both synaptic vesicles and calcium channels to the presynaptic active zone. Syntaxins function in this vesicle fusion process.
Syntaxin-1A is a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. Syntaxin-1A is a key protein in ion channel regulation and synaptic exocytosis.
Clinical significance
Syntaxins serve as a substrate for botulinum neurotoxin type C, a metalloprotease that blocks exocytosis and has high affinity for a molecular complex that includes the alpha-latrotoxin receptor which produces explosive exocytosis.
The expression level of STX1A is directly correlated with intelligence in Williams syndrome.
Interactive pathway map
Interactions
STX1A has been shown to interact with:
CPLX1,
CFTR,
NAPA,
RNF40,
SCNN1G,
SLC6A1,
|
https://en.wikipedia.org/wiki/SOCS3 | Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the SOCS3 gene.
This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.
SOCS3 is a conserved gene, found in across the animal kingdom, including Drosophila, chickens, and crocodiles.
Function
The expression of SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma.
For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3.
Overexpression of SOCS3 inhibits insulin signaling in adipose tissue and the liver, but not in muscle. But deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related insulin resistance.
SOCS3 contributes to both leptin resistance and insulin resistance as a result of increased ceramide synthesis. For that reason, studies have shown that removal of the SOCS gene prevents against insulin resistance in obesity
Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development.
The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase.
Interactions
SOCS3 has been shown to interact with:
Erythropoietin receptor,
G |
https://en.wikipedia.org/wiki/Interleukin%208%20receptor%2C%20beta | Interleukin 8 receptor, beta is a chemokine receptor. IL8RB is also known as CXCR2, and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name.
Function
The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein-activated second messenger system (Gi/o-coupled). This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. In addition, it binds ligands CXCL2, CXCL3, and CXCL5.
The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. IL8RB, IL8RA, which encodes another high affinity IL8 receptor, and IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36.
Mutations in CXCR2 cause hematological traits.
Senescence
Knock-down studies involving the chemokine receptor CXCR2 alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Also, ectopic expression of CXCR2 results in premature senescence via a p53-d |
https://en.wikipedia.org/wiki/TSG101 | Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.
Function
The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression.
The main role of TSG101 is to participate in ESCRT pathway. This pathway facilitates reverse topology budding and formation of multivesicular bodies (MVB) which delivers cargo destined for degradation to the lysosomes. TSG101 recognises short linear motif : P(T/S)AP via the UEV protein domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping |
https://en.wikipedia.org/wiki/FHL1 | Four and a half LIM domains protein 1 is a protein that in humans is encoded by the FHL1 gene.
Structure
LIM proteins, named for 'LIN11, ISL1, and MEC3,' are defined by the possession of a highly conserved double zinc finger motif called the LIM domain.
Role in muscle disorders
FHL1 has been shown to be heavily expressed in skeletal and cardiac muscles. In 2008 this was borne out by the discovery that defects in the FHL1 gene are responsible for a number of Muscular dystrophy-like muscle disorders, ranging from severe, childhood onset diseases through to adult-onset disorders similar to Limb girdle muscular dystrophy. At least 15 disease-causing mutations in this gene have been discovered. At present different research groups are using different terminology for these disorders, which include:
X-linked myopathy with postural muscle atrophy (XMPMA) An adult-onset muscle disorder known to affect families in Austria and the UK.
Reducing body myopathy (RBM) A rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. The effects of the disorder can be either severe, with onset of weakness at approximately five years, or adult onset, with weakness occurring in the late 20s, early 30s.
Scapuloperoneal (SP) syndrome Another adult-onset muscle disorder, especially affecting the shoulder girdle and legs.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Emery–Dreifuss muscular dystrophy
|
https://en.wikipedia.org/wiki/HF2 | HF2 may refer to:
Factor H, a glycoprotein.
Housefull 2, a 2012 Bollywood film featuring an ensemble cast. |
https://en.wikipedia.org/wiki/PLK1 | Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 (polo-like kinase 1) gene.
Structure
PLK1 consists of 603 amino acids and is 66kDa. In addition to the N-terminus kinase domain, there are two conserved polo-box regions of 30 amino acids at the C-terminus. Kinase activity is regulated at least in part, by the polo-boxes that are functionally important for both auto-inhibition and subcellular localization.
Localization
During interphase, PLK1 localizes to centrosomes. In early mitosis, it associates with mitotic spindle poles. A recombinant GFP-PLK1 protein localizes to centromere/kinetochore region, suggesting a possible role for chromosome separation.
Cell cycle regulation
Plk1 is an early trigger for G2/M transition. Plk1 supports the functional maturation of the centrosome in late G2/early prophase and establishment of the bipolar spindle. Plk1 phosphorylates and activates cdc25C, a phosphatase that dephosphorylates and activates the cyclinB/cdc2 complex. Plk phosphorylates and activates components of the anaphase-promoting complex (APC). The APC, which is activated by Fizzy-Cdc20 family proteins, is a cell cycle ubiquitin-protein ligase (E3) that degrades mitotic cyclins, chromosomal proteins that maintain cohesion of sister chromatids, and anaphase inhibitors. Abnormal spindle (Asp), a Polo kinase substrate, is a microtubule-associated |
https://en.wikipedia.org/wiki/HLA-DO | Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunodominant epitope selection. As a non-classical MHC class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in antigenic peptide chaperoning and loading, as opposed to its classical counterparts, which are polymorphic and involved in antigen presentation. Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body—namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells—indicate that it may be of physiological importance and has inspired further research. Although HLA-DM can be found without HLA-DO, HLA-DO is only found in complex with HLA-DM and exhibits instability in the absence of HLA-DM. The evolutionary conservation of both DM and DO, further denote its biological significance and potential to confer evolutionary benefits to its host.
Discovery
Studies on HLA-DO transfected fibroblast cells lines and on the HLA-DO mouse homolog, H-2O, provide most of the current knowledge on the protein. In 1985, the α- and β-chains were separately discovered, and in 1990, both chains were found to be co-expressed in one protein in H-2O. In contrast to other molecules of MHC class II, interferon gamma does not induce HLA-DO expr |
https://en.wikipedia.org/wiki/Gp180 | Term Gp180 may refer to:
PTPRC, an enzyme that is in humans encoded by the PTPRC gene
Metallocarboxypeptidase D, an enzyme class |
https://en.wikipedia.org/wiki/Dynasty%20Tour | The Dynasty Tour was a concert tour by the rock band Kiss.
Background
The Dynasty Tour, also known as "The Return of Kiss", was the first tour to feature the famous flying stunt by Gene Simmons. This was also the first tour to feature Ace Frehley's "lighted guitar" and his rocket-shooting guitar, where after his smoke-spewing guitar solo, the still-smoking guitar would float up. As it was floating upward, he would appear with another guitar, aim the neck at the floating guitar, shoot the rockets, and blow it up. John Elder Robison, who served as a technician for the band during the late 1970's, documented the lengths he went to create the elaborate effects for the tour. A trick was designed for Paul Stanley that involved his putting on a headset and shooting a laser out of his left eye to mock the effect seen in Kiss Meets the Phantom of the Park the year before. After several runthroughs, both Stanley and manager Bill Aucoin nixed the idea, citing the danger involved.
The tour, dubbed "The Return Of Kiss", also saw a decline in audience. Additional dates at the Pontiac Silverdome were cancelled. Reviews and recordings have confirmed the tour was also of poor musical quality. This was the last tour with Peter Criss on drums until 1996. He would later admit he would intentionally stop playing during shows just to upset the rest of the band.
This tour is also famous for being the only tour to feature songs from all four members’ solo albums. Simmons performed "Radioactive", |
https://en.wikipedia.org/wiki/Retinoic%20acid%20receptor%20alpha | Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a nuclear receptor that in humans is encoded by the RARA gene.
NR1B1 is a gene with a protein product and has a chromosomal location of 17q21.2. RARA codes for the nuclear hormone receptor retinoic acid receptor, alpha subtype, a transcription factor. There are another two subtypes of RARs: beta and gamma subtypes.
Function
Retinoid signaling is transduced by 2 families of nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), which form RXR/RAR heterodimers. In the absence of ligand, DNA-bound RXR/RARA represses transcription by recruiting the corepressors NCOR1, SMRT (NCOR2), and histone deacetylase. When ligand binds to the complex, it induces a conformational change allowing the recruitment of coactivators, histone acetyltransferases, and the basic transcription machinery.
Retinoic acid receptor-alpha, the protein, interacts with retinoic acid, a derivative of vitamin A, which plays an important role in cell growth, differentiation, and the formation of organs in embryonic development.
Once retinoic acid binds to the RAR, the heterodimer initiates transcription and allows for its target genes to be expressed.
Clinical significance
RA signaling has been correlated with several signaling pathways in early embryonic development. First, it participates in the formation of the embryonic axis, which establishes symmetry in the offspring |
https://en.wikipedia.org/wiki/8PB | 8PB may also refer to:
ABC NewsRadio, in Australia (Frequency callsign 8PB in the Northern Territory)
The Port of Bridgetown (Port callsign 8PB) |
https://en.wikipedia.org/wiki/Wilson%E2%80%93Cowan%20model | In computational neuroscience, the Wilson–Cowan model describes the dynamics of interactions between populations of very simple excitatory and inhibitory model neurons. It was developed by Hugh R. Wilson and Jack D. Cowan and extensions of the model have been widely used in modeling neuronal populations. The model is important historically because it uses phase plane methods and numerical solutions to describe the responses of neuronal populations to stimuli. Because the model neurons are simple, only elementary limit cycle behavior, i.e. neural oscillations, and stimulus-dependent evoked responses are predicted. The key findings include the existence of multiple stable states, and hysteresis, in the population response.
The model was inspired as the neural analog of Rayleigh–Bénard convection cloud patterns in fluid thermodynamics.
Mathematical description
The Wilson–Cowan model considers a homogeneous population of interconnected neurons of excitatory and inhibitory subtypes. All cells receive the same number of excitatory and inhibitory afferents, that is, all cells receive the same average excitation, x(t). The target is to analyze the evolution in time of number of excitatory and inhibitory cells firing at time t, and respectively.
The equations that describes this evolution are the Wilson-Cowan model:
where:
and are functions of sigmoid form that depends on the distribution of the trigger thresholds (see below)
is the stimulus decay function
and ar |
https://en.wikipedia.org/wiki/APEX1 | DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene.
Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication. All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as base excision repair (BER). The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. Splice variants have been found for this gene; all encode the same protein.
Interactions
APEX1 has been shown to interact with MUTYH, Flap structure-specific endonuclease 1 and XRCC1.
Aging
Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging. This finding is consistent with the theory that DNA damage is a primary cause of aging.
References
Further reading
External links |
https://en.wikipedia.org/wiki/TSC2 | Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.
Function
Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. Hamartin coded by the gene TSC1 functions as a facilitator of Hsp90 in chaperoning of Tuberin, therefore preventing its ubiquitination and degradation in the proteasome. Alternative splicing results in multiple transcript variants encoding different isoforms of the protein. Mutations in TSC2 can cause Lymphangioleiomyomatosis, a disease caused by the enlargement of tissue in the lungs, creating cysts and tumours and causing difficulty breathing. Because Tuberin regulates cell size, along with the protein Hamartin, mutations to TSC1 and TSC2 genes may prevent the control of cell growth in the lungs of individuals.
Cell Pathology
Cells from individuals with pathogenic mutations in the TSC2 gene display depletion of lysosomes, impairment of autophagy, and abnormal accumulation of glycogen. Defects in the autophagy-lysosome pathway are associated with excessive ubiquitination and degradation of LC3 and LAMP1/2 proteins.
Signaling Pathways
Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.
The defective degradation of glycogen by the autophagy-lysosome pathway is, at least in part, independent of impaired regulation of mTORC1 and |
https://en.wikipedia.org/wiki/RAS%20p21%20protein%20activator%201 | RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:
Inactivation of Ras from its active GTP-bound form to its inactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain
Mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains
The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues.
Domains
RasGAP contains one SH3 domain and two SH2 domains, a PH domain, a C2 domain, and a GAP domain.
Interactions
RAS p21 protein activator 1 has been shown to interact with:
ANXA6,
CAV2,
DNAJA3,
DOK1,
EPHB2,
EPHB3,
GNB2L1
HCK,
HRAS,
HTT,
|
https://en.wikipedia.org/wiki/Calcium/calmodulin-dependent%20protein%20kinase%20type%20II%20subunit%20alpha | Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), protein kinase , is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the CAMK2A gene.
Function
The product of the CAMK2A gene is an enzyme that belongs to the serine/threonine-specific protein kinase family, as well as the Ca2+/calmodulin-dependent protein kinase II subfamily. Ca2+ signaling is crucial for several aspects of synaptic plasticity at glutamatergic synapses. This enzyme is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Two transcript variants encoding distinct isoforms have been identified for this gene. According to a 2018 study by Bruno Reversade, the recessive mutation of CAMK2A in humans cause a syndrome of severe intellectual disability with growth retardation.
Interactions
CAMK2A has been shown to interact with:
Actinin alpha 4,
CDK5R1, and
DLG1.
References
Further reading
External links
EC 2.7.11 |
https://en.wikipedia.org/wiki/Coagulation%20factor%20XIII%2C%20A1%20polypeptide | Coagulation factor XIII A chain is a protein that in humans is encoded by the F13A1 gene.
Function
This gene encodes the coagulation factor XIII A subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as plasma carrier molecules. Platelet factor XIII is composed of just 2 A subunits, which are identical to those of plasma origin. Upon cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion.
Interactions
Coagulation factor XIII, A1 polypeptide has been shown to interact with F13B.
References
Further reading |
https://en.wikipedia.org/wiki/HBG2 | Hemoglobin subunit gamma-2 is a protein that in humans is encoded by the HBG2 gene.
Function
The gamma globin genes (HBG1 and HBG2, this gene) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5' - epsilon – gamma-G – gamma-A – delta – beta - 3'.
References
Further reading
External links
Hemoglobins |
https://en.wikipedia.org/wiki/Sterol%20regulatory%20element-binding%20protein%201 | Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene.
This gene is located within the Smith–Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. The isoforms are SREBP-1a and SREBP-1c (the latter also called ADD-1). SREBP-1a is expressed in the intestine and spleen, whereas SREBP-1c is mainly expressed in liver, muscle, and fat (among other tissues).
Expression
The proteins encoded by this gene are transcription factors that bind to a sequence in the promoter of different genes, called sterol regulatory element-1 (SRE1). This element is a decamer (oligomer with ten subunits) flanking the LDL receptor gene and other genes involved in, for instance, sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family.
SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell.
SREBP- |
https://en.wikipedia.org/wiki/SIN3A | Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
Function
The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex.
Interactions
SIN3A has been shown to interact with:
CABIN1
HBP1,
HDAC1,
HDAC9,
Histone deacetylase 2,
Host cell factor C1,
IKZF1,
ING1,
KLF11,
MNT,
MXD1,
Methyl-CpG-binding domain protein 2,
Nuclear receptor co-repressor 2,
OGT,
PHF12,
Promyelocytic leukemia protein,
RBBP4,
RBBP7,
SAP130,
SAP30,
SMARCA2,
SMARCA4,
SMARCC1,
SUDS3,
TAL1, and
Zinc finger and BTB domain-containing protein 16.
See also
Transcription coregulator
References
Further reading
External links
Gene expression
Transcription coregulators |
https://en.wikipedia.org/wiki/ARF1 | ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.
Function
ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.
The major mechanism of action of Brefeldin A is through inhibition of ARF1.
Interactions
ARF1 has been shown to interact with:
CHRM3,
COPB1,
GGA3, and
PLD2.
References
Further reading
External links |
https://en.wikipedia.org/wiki/ERBB4 | Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.
Function
Receptor tyrosine-protein kinase erbB-4 is a receptor tyrosine kinase that is a member of the epidermal growth factor receptor family. ERBB4 is a single-pass type I transmembrane protein with multiple furin-like cysteine rich domains, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins-2, -3 and -4, heparin-binding EGF-like growth factor and betacellulin. Ligand binding induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment.
Clinical significance
Mutations in this gene have been associated with cancer. Other single-nucleotide polymorphisms and a risk haplotype have been linked to schizophrenia. Single-nucleotide polymorphisms in ERBB4 have also been found in a study of patients with familial amyotrophic lateral sclerosis type 19.
Interactions
ERBB4 has been shown to interact with:
DLG4
NRG1,
STAT5A, and
YAP1.
References
Further reading
External links
Tyrosine kinase receptors |
https://en.wikipedia.org/wiki/PPP2CA | Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that (in humans) is encoded by the PPP2CA gene.
Function
This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes an alpha isoform of the catalytic subunit.
Interactions
PPP2CA has been shown to interact with:
Bcl-2,
Bestrophin 1,
CCNG2,
CTTNBP2NL,
CTTNBP2,
Cyclin-dependent kinase 2,
Cyclin-dependent kinase 6,
FAM40A,
IGBP1,
MOBKL3,
PPP2R1A,
PPP2R1B,
PPP2R2A,
PPP2R3B,
PPP2R5A,
PPP2R5B,
PPP2R5C,
PPP2R5D,
PPP2R5E,
STRN3,
STRN, and
TLX1.
See also
PPP2CB
References
Further reading |
https://en.wikipedia.org/wiki/MAP2K2 | Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2.
Function
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK3/ERK1.
The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases.
The inhibition or degradation of this kinase is found to be involved in the pathogenesis of Yersinia and anthrax.
Interactions
MAP2K2 has been shown to interact with MAPK3 and ARAF.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome
EC 2.7.12 |
https://en.wikipedia.org/wiki/MAP3K7 | Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.
Structure
TAK1 is an evolutionarily conserved kinase in the MAP3 K family and clusters with the tyrosine-like and sterile kinase families. The protein structure of TAK1 contains an N (residues 1–104)- and C (residues 111–303)-terminus connected through the hinge region (Met 104-Ser 111). The ATP binding pocket is located in the hinge region of the kinase. Additionally, TAK1 has a catalytic lysine (Lys63) in the active site. Crystal structure of TAK1-ATP have shown that ATP forms two hydrogen bonds with residues Ala 107 and Glu 105. Further hydrogen bonding is observed to Asp 175, which is the leading residue of the DFG motif. This residue is thought to interact with Lys 63 through polar interactions and is catalytically important for phosphate transfer to substrate molecules. Critical for the TAK1-TAB1 complex is a helical loop around Phe 484, which provides extensive surface contact between the two proteins.
Signaling
The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates signal transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. TAK1 is a central regulator of cell death and is activated through a diverse set of intra- and extracellular stimuli. TAK1 regulates cell surviva |
https://en.wikipedia.org/wiki/TAP1 | Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the TAP1 gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2.
Function
The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease.
See also
ATP-binding cassette transporter
Interactions
TAP1 has been shown to interact with:
HLA-A, and
Tapasin.
References
Further reading
External links
ATP-binding cassette transporters |
https://en.wikipedia.org/wiki/TNNI3 | Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene.
It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.
The TNNI3 gene encoding cardiac troponin I (cTnI) is located at 19q13.4 in the human chromosomal genome. Human cTnI is a 24 kDa protein consisting of 210 amino acids with isoelectric point (pI) of 9.87. cTnI is exclusively expressed in adult cardiac muscle.
Gene evolution
cTnI has diverged from the skeletal muscle isoforms of TnI (slow TnI and fast TnI) mainly with a unique N-terminal extension. The amino acid sequence of cTnI is strongly conserved among mammalian species (Fig. 1). On the other hand, the N-terminal extension of cTnI has significantly different structures among mammal, amphibian and fish.
Tissue distribution
TNNI3 is expressed as a heart specific gene. Early embryonic heart expresses solely slow skeletal muscle TnI. cTnI begins to express in mouse heart at approximately embryonic day 10, and the level gradually increases to one-half of the total amount of TnI in the cardiac muscle at birth. cTnI completely replaces slow TnI in the mouse heart approximately 14 days after birth
Protein structure
Based on in vitro
structure-function relationship studies, the structure of cTnI can be divided into six functional segments: a) a cardiac-specific N-terminal extension (residue 1–30) that is not present in fast TnI and slow TnI; b)
an N-terminal region (residue 42–79) that binds the |
https://en.wikipedia.org/wiki/AKT2 | AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.
Function
This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins.
AKT2 has important roles in controlling glycogenesis, gluconeogenesis, and glucose transport as part of the insulin signal transduction pathway.
Clinical significance
The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.
Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that Akt2 plays a key role in signal transduction downstream of the insulin receptor. Mice lacking Akt2 show worse outcome in breast cancer initiated by the large T antigen as well as the neu oncogene.
Interactions
AKT2 has been shown to interact with:
APPL1,
CHUK,
SH3RF1 and
TCL1A.
References
Further reading
External links
EC 2.7.11
Protein kinases |
https://en.wikipedia.org/wiki/Importin%20subunit%20alpha-5 | Importin subunit alpha-5 is a protein that in humans is encoded by the KPNA1 gene.
Interactions
Importin subunit alpha-5 has been shown to interact with KPNB1 and UBR5.
References
Further reading
Armadillo-repeat-containing proteins |
https://en.wikipedia.org/wiki/UCP2 | Mitochondrial uncoupling protein 2 is a protein that in humans is encoded by the UCP2 gene.
Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate, or uncouple, oxidative phosphorylation from ATP synthesis by dissipating the mitochondrial membrane potential as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells, which reduces production of reactive oxygen species (ROS).
In contrast to UCP1 and UCP3, which are primarily expressed in adipose and smooth muscle, UCP2 is expressed on many different tissues including the kidney, liver, GI tract, brain, and skeletal muscle.
The exact mechanisms of anion transfer by UCPs are not known. UCPs contain the three homologous protein domains of MACPs. Although it was originally thought to play a role in non-shivering thermogenesis, obesity, diabetes and atherosclerosis, it now appears that the main function of UCP2 is the control of mitochondria-derived reactive oxygen species.
Chromosomal order is 5'-UCP3-UCP2-3'.
See also
Uncoupling protein
References
Further reading
Solute carrier family |
https://en.wikipedia.org/wiki/IRS2 | Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.
Function
This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment.
Mice lacking IRS2 have a diabetic phenotype as well as a 40% reduction in brain mass.
Interactions
IRS2 has been shown to interact with:
PLCG1,
SOCS1, and
PIK3R1,
References
Further reading |
https://en.wikipedia.org/wiki/Cadherin-2 | Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the CDH2 gene. CDH2 has also been designated as CD325 (cluster of differentiation 325).
Cadherin-2 is a transmembrane protein expressed in multiple tissues and functions to mediate cell–cell adhesion. In cardiac muscle, Cadherin-2 is an integral component in adherens junctions residing at intercalated discs, which function to mechanically and electrically couple adjacent cardiomyocytes. Alterations in expression and integrity of Cadherin-2 has been observed in various forms of disease, including human dilated cardiomyopathy. Variants in CDH2 have also been identified to cause a syndromic neurodevelopmental disorder.
Structure
Cadherin-2 is a protein with molecular weight of 99.7 kDa, and 906 amino acids in length. Cadherin-2, a classical cadherin from the cadherin superfamily, is composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Cadherin-2, as well as other cadherins, interact with Cadherin-2 on an adjacent cell in an anti-parallel conformation, thus creating a linear, adhesive "zipper" between cells.
Function
Cadherin-2, originally named Neural cadherin for its role in neural tissue, plays a role in neurons and later was found to also play a role in cardiac muscle and in cancer metastasis. Cadherin-2 is a transmembrane, homophilic glycoprotein belonging to the calcium-dependent cell adhesion molecule family. Thes |
https://en.wikipedia.org/wiki/Interleukin-6%20receptor | Interleukin 6 receptor (IL6R) also known as CD126 (Cluster of Differentiation 126) is a type I cytokine receptor.
Function
Interleukin 6 (IL6) is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in immune response. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer.
In melanocytes IL6R gene expression may be regulated by MITF.
Structure
The IL6 receptor is a protein complex consisting of an IL-6 receptor subunit (IL6R) and interleukin 6 signal transducer Glycoprotein 130. IL6R also denotes the human gene encoding this subunit. Alternatively spliced transcript variants encoding distinct isoforms have been reported. IL6R subunit is also shared by many other cytokines.
Interactions
Interleukin-6 receptor has been shown to interact with Interleukin 6 and ciliary neurotrophic factor.
See also
Cluster of differentiation
Anti-IL-6
Tocilizumab, a monoclonal antibody against IL6R
Sarilumab, a monoclonal antibody against IL6R
References
Further reading
External links
Type I cytokine receptors
Clusters of differentiation |
https://en.wikipedia.org/wiki/POLR2C | DNA-directed RNA polymerase II subunit RPB3 is an enzyme that in humans is encoded by the POLR2C gene.
Function
This gene encodes the third largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a cysteine rich region and exists as a heterodimer with another polymerase subunit, POLR2J. These two subunits form a core subassembly unit of the polymerase. A pseudogene has been identified on chromosome 21.
Interactions
POLR2C has been shown to interact with:
ATF4,
CCHCR1,
Myogenin,
POLR2A,
POLR2B,
POLR2E and
POLR2F,
POLR2G,
POLR2H,
POLR2J,
POLR2K,
POLR2L, and
TAF15.
References
Further reading |
https://en.wikipedia.org/wiki/POLR2E | DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene.
This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11.
Interactions
POLR2E has been shown to interact with TAF15, POLR2C, POLR2G, POLR2H, POLR2A, POLR2B, POLR2L and GTF2F2.
References
Further reading |
https://en.wikipedia.org/wiki/Retinoblastoma-like%20protein%202 | Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.
Interactions
Retinoblastoma-like protein 2 has been shown to interact with:
BRCA1,
BRF1
C-Raf,
Cyclin E1,
Cyclin-dependent kinase 2,
HDAC1,
Prohibitin, and
RBBP8.
See also
Pocket protein family
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/S100-A4 | Protein S100-A4 (S100A4) is a protein that in humans is encoded by the S100A4 gene.
Function
The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified.
Interactions
S100A4 has been shown to interact with S100 calcium binding protein A1.
Therapeutic targeting for cancer
S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. Research demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of th |
https://en.wikipedia.org/wiki/SGK | Serine/threonine-protein kinases SGK represent a kinase subfamily with orthologs found across animal clades and in yeast (compare Treefam family TF320906). In most vertebrates, including humans, there are three isoforms encoded by the genes SGK1, SGK2, and SGK3. The name Serum/glucocorticoid-regulated kinase refers to the first cloning of a SGK family member from a cDNA library screen for genes upregulated by the glucocorticoid dexamethasone in a rat mammary epithelial tumor cell line.
The first human family member (human SGK1) was cloned in a screen of hepatocellular genes regulated in response to cellular hydration or swelling.
The term SGK is also used as a synonym for SGK1.
Function
Among the three SGK genes, the SGK1 gene is the most intensively studied. This gene encodes a serine/threonine protein kinase that is highly similar to the rat serum-and glucocorticoid-induced protein kinase (SGK). This gene was identified in a screen of hepatocellular genes regulated in response to cellular hydration or swelling. Cellular hydration is a catabolic signal, stimulating glycogenolysis and proteolysis, and inhibiting protein and glycogen synthesis. This kinase has been shown to be important in activating certain potassium, sodium, and chloride channels. Expression of this gene in hepatocytes is stimulated by transforming growth factor-beta (TGF-beta), which participates in the pathophysiology of diabetic complications. Since both TGF-beta expression and SGK expression are ele |
https://en.wikipedia.org/wiki/HMGA1 | High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.
Function
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin organization, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells.
HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins.
HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive post-transcriptional modifications in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks. It has little secondary structure in solution but assumes distinct conformations when bound to substrates such as DNA or other proteins. HMGA1 proteins have high amounts of diverse posttranslational modifications and are located mainly in the nucleus, especially in heterochromatin, but also in mitochondria and the cytoplasm.
Recently it has been shown that HMGA1 proteins, HMGA1a and HMGA1b, can cros |
https://en.wikipedia.org/wiki/HNRNPA1 | Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the HNRNPA1 gene. Mutations in hnRNP A1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy.
Function
This gene belongs to the A/B 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 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. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs in the N-terminal domain which are pivotal for RNA specificity and binding. The protein also has a glycine rich arginine-glycine-glycine (RGG) region called the RGG box which enables protein and RNA binding. It affects many critical genes that are responsible for controlling metabolic pathways at the transcriptional, post-transcriptional, translation, and post-translation levels. It is one of the most abundant core proteins of hnRNP complexes and it is localized to the nucleoplasm. This protein, along with other hnRNP proteins, is exported from the nucleus, probably bound to mRNA, and is immediately re-imported. Its M9 nuclear locali |
https://en.wikipedia.org/wiki/HSF1 | Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the HSF1 gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.
Structure
Human HSF1 consists of several domains which regulate its binding and activity.
DNA-Binding Domain (DBD)
This N-terminal domain of approximately 100 amino acids is the most highly conserved region in the HSF protein family and consists of a helix-turn-helix loop. The DBD of each HSF1 monomer recognizes the sequence nGAAn on target DNA. Repeated sequences of the nGAAn pentamer constitute heat shock elements (HSEs) for active HSF1 trimers to bind.
Oligomerization Domain (Leucine Zipper Domains)
The two regions responsible for oligomerization between HSF1 monomers are leucine zipper (LZ) domains 1-3 and 4 (these regions are also commonly referred to as HR-A/B and HR-C). LZ1-3 is situated just downstream of the DBD while LZ4 is located between the RD and the C-terminal TAD. Under non-stress conditions, spontaneous HSF1 activation is negatively regulated by the interaction between LZ1-3 and LZ4. When induced by stress, the LZ1-3 region breaks away from the LZ4 region and forms a trimer with other HSF1 LZ1-3 domains to form a triple coiled-coil.
Regulatory Domain (RD)
The structures of the C-terminal RD and TAD of HSF1 have not been clearly resolved due to their dynamic nature. However |
https://en.wikipedia.org/wiki/POLR2B | DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.
This gene encodes the second largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit, in combination with at least two other polymerase subunits, forms a structure within the polymerase that maintains contact in the active site of the enzyme between the DNA template and the newly synthesized RNA.
Interactions
POLR2B has been shown to interact with POLR2C, POLR2E, POLR2H and POLR2L.
References
Further reading |
https://en.wikipedia.org/wiki/RELB | Transcription factor RelB is a protein that in humans is encoded by the RELB gene.
Interactions
RELB has been shown to interact with NFKB2, NFKB1, and C22orf25.
Activation and function
In resting cells, RelB is sequestered by the NF-κB precursor protein p100 in the cytoplasm. A select set of TNF-R superfamily members, including lymphotoxin β-receptor (LTβR), BAFF-R, CD40 and RANK, activate the non-canonical NF-κB pathway. In this pathway, NIK stimulates the processing of p100 into p52, which in association with RelB appears in the nucleus as RelB:p52 NF-κB heterodimers. RelB:p52 activates the expression homeostatic lymphokines, which instruct lymphoid organogenesis and determine the trafficking of naive lymphocytes in the secondary lymphoid organs.
Recent studies has suggested that the functional non-canonical NF-κB pathway is modulated by canonical NF-κB signalling. For example, syntheses of the constituents of the non-canonical pathway, viz RelB and p52, are controlled by canonical IKK2-IκB-RelA:p50 signalling. Moreover, generation of canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are mechanistically interlinked. These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway.
Most intriguingly, a recent study identified that TNF-induced can |
https://en.wikipedia.org/wiki/MAP2K4 | Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.
MAP2K4 encodes a dual-specificity kinase that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains a kinase domain that is phosphorylated and activated by MAP3K1(aka MEKK1). MAP2K4 contains multiple amino acid sites that are phosphorylated and ubiquitinated. Genetic studies using Map2k4 knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation. Analysis of chimeric mice identified a role for Map2k4 in T cell cytokine production and proliferation. Map2k4-deficient chimeric mice frequently develop lymphadenopathy. MAP2K4 is altered in 1.97% of all human cancers.
Interactions
MAP2K4 has been shown to interact with:
MAP3K1,
FLNC,
MAPK8,
MAPK8IP3 and
AKT1.
ITCH.
References
Further reading
Mitogen-activated protein kinases
EC 2.7.11 |
https://en.wikipedia.org/wiki/KHDRBS1 | KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the KHDRBS1 gene.
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression.
Function
Sam68 (the Src-Associated substrate in Mitosis of 68 kDa) is officially called KHDRBS1 (KH domain containing, RNA binding, signal transduction associated 1). Sam68 is a KH-type RNA binding protein that recognizes U(U/A)AA direct repeats with relative high affinity. Sam68 is predominantly nuclear and its major function in the nucleus is to regulate alternative splicing by recognizing RNA sequences neighboring the included/excluded exon(s).
Clinical significance
Sam68 influences the alternative splicing of a number of genes central to processes such as neurogenesis and adipogenesis as well as diseases such as spinal muscular atrophy (SMA) and cancer.
Neurogenesis
Sam68 was demonstrated to be involved in the alternative splicing of mRNAs implicated in normal neurogenesis using splicing-sensitive microarrays. Sam68 was also shown to participate in the epithelial-to-mesenchymal transition by regulating the alternative splicing of SF2/ASF. Sam68 was sh |
https://en.wikipedia.org/wiki/Adenosine%20A2A%20receptor | {{DISPLAYTITLE:Adenosine A2A receptor}}
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it.
Structure
This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alpha helices, as well as an extracellular N-terminus and an intracellular C-terminus. Furthermore, located in the intracellular side close to the membrane is a small alpha helix, often referred to as helix 8 (H8). The crystallographic structure of the adenosine A2A receptor reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin). Below this primary (orthosteric) binding pocket lies a secondary (allosteric) binding pocket. The crystal-structure of A2A bound to the antagonist ZM241385 (PDB code: 4EIY) showed that a sodium-ion can be found in this location of the protein, thus giving it the name 'sodium-ion binding pocket'.
Heteromers
The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. Heteromers consisting of adenosine A1/A2A, dopamine D2/A2A and D3/A2A, glutamate mGluR5/A2A and cannabinoid CB1/A2A have all been observed, as well as CB1/A2A/ |
https://en.wikipedia.org/wiki/CRKL | Crk-like protein is a protein that in humans is encoded by the CRKL gene.
Function
v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL. In addition, CRKL has oncogenic potential.
CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.
Interactions
CRKL has been shown to interact with:
Abl gene,
BCAR1,
BCR gene,
CBLB,
CD117,
CD34,
Cbl gene,
Dock2,
EPOR,
GAB1,
GAB2,
INPP5D,
MAP4K1,
MAP4K5,
NEDD9,
PIK3R2,
Paxillin
RAPGEF1,
RICS,
STAT5A,
Syk, and
WAS.
See also
Crk
References
Further reading
External links |
https://en.wikipedia.org/wiki/DLG1 | Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the SAP97 gene.
SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein Dlg1 (the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in epithelial cells. In the brain it is involved in the trafficking of ionotropic receptors from the endoplasmic reticulum to the plasma membrane, and may be involved in the trafficking AMPAR during synaptic plasticity.
Function
SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain. There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.
SAP97's function has been investigated by reducing its expression by knockout or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function. Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.
Clinical significance
Mutations in DLG1 are associated to Crohn's Disease.
Structure
SAP97's protein structure consists of an alternatively-spliced n-terminal domain, three PDZ domains, an SH3 domain, hook domain, I3 domain, and fin |
https://en.wikipedia.org/wiki/Interleukin%208%20receptor%2C%20alpha | Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD181 (cluster of differentiation 181). The IUPHAR Committee on Receptor Nomenclature and Drug Classification use the HGNC recommended name, CXCR1.
Function
The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein-activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. IL8RA, IL8RB, which encodes another high affinity IL8 receptor, and IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.
Clinical significance
Blocking CXCR1 (e.g., with repertaxin) inhibits some human breast cancer stem cells (in vitro and in mice).
In malignant melanoma expression of CXCR1 at the cell surface is present, independent of the cancers stage. It is thought to have a role in the cell growth and angiogenesis required for tumour survival. In this way it has been identified as a potential therapeutic target.
CXCR1 can be |
https://en.wikipedia.org/wiki/POU2F1 | POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the POU2F1 gene.
Interactions
POU2F1 has been shown to interact with:
EPRS,
Glucocorticoid receptor,
Glyceraldehyde 3-phosphate dehydrogenase,
Host cell factor C1,
Ku80,
MNAT1
NPAT,
Nuclear receptor co-repressor 2,
POU2AF1,
RELA,
Retinoid X receptor alpha,
SNAPC4,
Sp1 transcription factor, and
TATA binding protein.
See also
Octamer transcription factor
References
Further reading
External links
POU-domain proteins |
https://en.wikipedia.org/wiki/Tight%20junction%20protein%201 | Zonula occludens-1 ZO-1, also known as Tight junction protein-1 is a 220-kD peripheral membrane protein that is encoded by the TJP1 gene in humans. It belongs to the family of zonula occludens proteins (ZO-1, ZO-2, and ZO-3), which are tight junction-associated proteins and of which, ZO-1 is the first to be cloned. It was first isolated in 1986 by Stevenson and Goodenough using a monoclonal antibody raised in rodent liver to recognise a 225-kD polypeptide in whole liver homogenates and in tight junction-enriched membrane fractions. It has a role as a scaffold protein which cross-links and anchors Tight Junction (TJ) strand proteins, which are fibril-like structures within the lipid bilayer, to the actin cytoskeleton.
Function
This gene encodes a protein located on a cytoplasmic membrane surface of intercellular tight junctions. The encoded protein may be involved in signal transduction at cell–cell junctions. Two transcript variants encoding distinct isoforms have been identified for this gene.
Interactions
Tight junction protein 1 has been shown to interact with:
F11 receptor,
GJA3,
GJA8,
Gap junction protein, alpha 1,
KIRREL,
MLLT4,
Occludin,
TJP3, and
Tight junction protein 2.
See also
Tight junction
References
Further reading
External links |
https://en.wikipedia.org/wiki/Melanocortin%204%20receptor | Melanocortin 4 receptor (MC4R) is a melanocortin receptor that in humans is encoded by the gene. It encodes the MC4R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.
Clinical significance
In 2009, two very large genome-wide association studies of body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the MC4R gene with insulin resistance, obesity, and other anthropometric traits. MC4R may also have clinical utility as a biomarker for predicting individual susceptibility to drug-induced adverse effects causing weight gain and related metabolic abnormalities. Another GWAS performed in 2012 identified twenty SNPs located ~190 Kb downstream of MC4R in association with severe antipsychotic-induced weight gain. This locus overlapped with the region previously identified in the 2009 studies. The rs489693 polymorphism, in particular, sustained a statistically robust signal across three replication cohorts and demonstrated consistent recessive effects. This finding was replicated again by another research group in the following year. In accordance with the above, MC4 receptor agonists have garnered interest as potential treatments for obesity and insulin resistance, while MC4 receptor antagonists have attracted interest as potential treat |
https://en.wikipedia.org/wiki/NFE2L2 | Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
NRF2 appears to participate in a complex regulatory network and performs a pleiotropic role in the regulation of metabolism, inflammation, autophagy, proteostasis, mitochondrial physiology, and immune responses. Several drugs that stimulate the NFE2L2 pathway are being studied for treatment of diseases that are caused by oxidative stress.
A mechanism for hormetic dose responses is proposed in which Nrf2 may serve as an hormetic mediator that mediates a vast spectrum of chemopreventive processes.
Structure
NRF2 is a basic leucine zipper (bZip) transcription factor with a Cap “n” Collar (CNC) structure. NRF2 possesses seven highly conserved domains called NRF2-ECH homology (Neh) domains. The Neh1 domain is a CNC-bZIP domain that allows Nrf2 to heterodimerize with small Maf proteins (MAFF, MAFG, MAFK). The Neh2 doma |
https://en.wikipedia.org/wiki/POLR2G | DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.
This gene encodes the seventh largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, the association of this subunit with the polymerase under suboptimal growth conditions indicates it may play a role in regulating polymerase function.
Interactions
POLR2G has been shown to interact with TAF15, POLR2C, POLR2H and POLR2E.
References
Further reading |
https://en.wikipedia.org/wiki/POLR2H | DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene.
This gene encodes one of the essential subunits of RNA polymerase II that is shared by the other two eukaryotic DNA-directed RNA polymerases, I and III.
Interactions
POLR2H has been shown to interact with POLR2C, POLR2G, POLR2A, POLR2B and POLR2E.
References
Further reading |
https://en.wikipedia.org/wiki/TNNT2 | Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.
The TNNT2 gene is located at 1q32 in the human chromosomal genome, encoding the cardiac muscle isoform of troponin T (cTnT). Human cTnT is an ~36-kDa protein consisting of 297 amino acids including the first methionine with an isoelectric point (pI) of 4.88. It is the tropomyosin- binding and thin filament anchoring subunit of the troponin complex in cardiac muscle cells. TNNT2 gene is expressed in vertebrate cardiac muscles and embryonic skeletal muscles.
Structure
Cardiac TnT is a 35.9 kDa protein composed of 298 amino acids. Cardiac TnT is the largest of the three troponin subunits (cTnT, troponin I (TnI), troponin C (TnC)) on the actin thin filament of cardiac muscle. The structure of TnT is asymmetric; the globular C-terminal domain interacts with tropomyosin (Tm), TnI and TnC, and the N-terminal tether which strongly binds Tm. The N-terminal region of TnT is alternatively spliced, accounting for multiple isoforms observed in cardiac muscle.
Function
As part of the Troponin complex, the function of cTnT is to regulate muscle contraction. The N-terminal region of TnT that strongly binds actin most likely moves with Tm and actin during strong myos |
https://en.wikipedia.org/wiki/Cyclin%20D3 | G1/S-specific cyclin-D3 is a protein that in humans is encoded by the CCND3 gene.
Function
The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation.
Clinical significance
Mutations in CCND3 are implicated in cases of breast cancer.
Interactions
Cyclin D3 has been shown to interact with:
AKAP8,
CDC2L1,
CDKN1B,
CRABP2,
Cyclin-dependent kinase 4,
Cyclin-dependent kinase 6,
EIF3K, and
Retinoic acid receptor alpha.
See also
Cyclin
Cyclin D
References
Further reading
Cell cycle regulators |
https://en.wikipedia.org/wiki/Cyclin-dependent%20kinase%207 | Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene.
The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression.
This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle.
Clinical significance e.g. cancer
Given that CDK7 is involved in two important regulation roles, it's expected that CDK7 regulation may play a role in cancerous cells. Cells from breast cancer tumors were found to have elevated levels of CDK7 and Cyclin H when compared to normal breast cells. It was also found that the higher levels were generally found in ER-positive breast cancer. Together, these findings indicate that CDK7 therapy might make sense for some breast cancer patients. Further confirming these findings, recent research indicates that inhibition of CDK7 may be an effective therapy for HER2-positive breast cancers, even overcoming therapeutic resistance. THZ1 was tested on HER2-positive breast cancer cells and e |
https://en.wikipedia.org/wiki/NFATC2 | Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.
Function
This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
Clinical significance
Translocation forming an in frame fusions product between EWSR1 gene and the NFATc2 gene has been described in bone tumor with a Ewing sarcoma-like clinical appearance. The translocation breakpoint led to the loss of the controlling elements of the NFATc2 protein and the fusion of the N terminal region of the EWSR1 gene conferred constant activation of the protein.
Interactions
NFATC2 has been shown to interact with MEF2D, EP300, IRF4 and Protein kinase Mζ. Prostaglandin F2alpha stimulates a NFCT2 pathway stimulating growth of skeletal muscle cells.
References
Further reading
External links
Transcription factors
Human proteins |
https://en.wikipedia.org/wiki/P2RX7 | P2X purinoceptor 7 is a protein that in humans is encoded by the P2RX7 gene.
The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced variants which would encode different isoforms have been identified although some fit nonsense-mediated decay criteria.
The receptor is found in the central and peripheral nervous systems, in microglia, in macrophages, in uterine endometrium, and in the retina. The P2X7 receptor also serves as a pattern recognition receptor for extracellular ATP-mediated apoptotic cell death, regulation of receptor trafficking, mast cell degranulation, and inflammation.
Structure and kinetics
The P2X7 subunits can form homomeric receptors only with a typical P2X receptor structure.
The P2X7 receptor is a ligand-gated cation channel that opens in response to ATP binding and leads to cell depolarization. The P2X7 receptor requires higher levels of ATP than other P2X receptors; however, the response can be potentiated by reducing the concentration of divalent cations such as calcium or magnesium. Continued binding leads to increased permeability to N-methyl-D-glucamine (NMDG+). P2X7 receptors do not become desensitized readily and continued signaling leads to the aforementioned increased permeability and an increase in current amplitude.
Pharmacology
Agonists
P2X7 receptors respond to BzATP more readily than ATP. ADP and AMP are weak agonists of P2X7 receptors, but a brief exposure to ATP can increase their |
https://en.wikipedia.org/wiki/POLR2F | DNA-directed RNA polymerases I, II, and III subunit RPABC2 is a protein that in humans is encoded by the POLR2F gene.
This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes, that is also shared by the other two DNA-directed RNA polymerases. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template.
Interactions
POLR2F has been shown to interact with POLR2C.
See also
RNA polymerase II
References
Further reading |
https://en.wikipedia.org/wiki/POLR2L | DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.
Function
This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases.
Interactions
POLR2L has been shown to interact with POLR2C, POLR2A, POLR2B and POLR2E.
References
Further reading |
https://en.wikipedia.org/wiki/APOA5 | Apolipoprotein A-V is a protein that in humans is encoded by the APOA5 gene on chromosome 11. It is significantly expressed in liver. The protein encoded by this gene is an apolipoprotein and an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of several lipoprotein fractions including VLDL, HDL, chylomicrons. It is believed that apoA-V affects lipoprotein metabolism by interacting with LDL-R gene family receptors. Considering its association with lipoprotein levels, APOA5 is implicated in metabolic syndrome. The APOA5 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
Discovery
The gene for apolipoprotein A5 (APOA5, gene ID 116519, OMIM accession number – 606368) was originally found by comparative sequencing of human and mice DNA as a last member of the gene cluster of apolipoproteins APOA1/APOC3/APOA4/APOA5, located on human chromosome 11 at position 11q23. The creation of two mice models (APOA5 transgenic and APOA5 knock-out) confirmed the important role of this gene in plasma triglyceride determination. The transgenic mice had lower and the knock-out mice higher levels of plasma triglycerides, while plasma cholesterol levels remained unchanged in both animal models. A Dutch group simultaneously described an identical gene as apolipoprotein which it is associated with the early phase of liver regeneration, but failed to recognise its important role in the de |
https://en.wikipedia.org/wiki/ELK1 | ETS Like-1 protein Elk-1 is a protein that in humans is encoded by the ELK1. Elk-1 functions as a transcription activator. It is classified as a ternary complex factor (TCF), a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences. Elk1 plays important roles in various contexts, including long-term memory formation, drug addiction, Alzheimer's disease, Down syndrome, breast cancer, and depression.
Structure
As depicted in Figure 1, the Elk1 protein is composed of several domains. Localized in the N-terminal region, the A domain is required for the binding of Elk1 to DNA. This region also contains a nuclear localization signal (NLS) and a nuclear export signal (NES), which are responsible for nuclear import and export, respectively. The B domain allows Elk1 to bind to a dimer of its cofactor, serum response factor (SRF). Located adjacent to the B domain, the R domain is involved in suppressing Elk1 transcriptional activity. This domain harbors the lysine residues that are likely to undergo SUMOylation, a post-translational event that strengthens the inhibition function of the R domain. The D domain plays the key role of binding to active Mitogen-activated protein kinases (MAPKs). Located in the C-terminal region of Elk1, the C domain includes the amino acids that actually become phosphorylated by MAPKs. In this region, Serine 383 and 389 are key sites that need to be phosphorylated for Elk1-mediated tran |
https://en.wikipedia.org/wiki/IGFBP2 | Insulin-like growth factor-binding protein 2 is a protein that in humans is encoded by the IGFBP2 gene.
References
Further reading |
https://en.wikipedia.org/wiki/PAK2 | Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene.
PAK2 is one of three members of Group I PAK family of serine/threonine kinases. The PAKs are evolutionary conserved. PAK2 and its cleaved fragment localize in both the cytoplasmic or nuclear compartments. PAK2 signaling modulates apoptosis, endothelial lumen formation, viral pathogenesis, and cancer including, breast, hepatocarcinoma, and gastric and cancer, at-large.
Discovery
The human PAK2 was identified as a downstream effector of Rac or Cdc42.
Gene and spliced variants
The PAK2 gene is about 92.7-kb long. The gene contains 15 exons and generates three alternatively spliced transcripts - two of which code proteins of 524 amino acids and 221 amino acids, while the third one is a 371-bp non-coding RNA transcript(Gene from review) There are two transcripts generated from the murine PAK2 gene, a 5.7-kb transcript coding a 524 amino acids long polypeptide and a 1.2-kb long non-coding RNA transcript.
Protein domains
Similar to PAK1, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation.
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. T |
https://en.wikipedia.org/wiki/POLR2J | DNA-directed RNA polymerase II subunit RPB11-a is an enzyme that in humans is encoded by the POLR2J gene.
Function
This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene exists as a heterodimer with another polymerase subunit; together they form a core subassembly unit of the polymerase. Two similar genes are located nearby on chromosome 7q22.1 and a pseudogene is found on chromosome 7p13.
Interactions
POLR2J has been shown to interact with:
Apoptosis antagonizing transcription factor,
POLR2C, and
SATB1.
References
Further reading |
https://en.wikipedia.org/wiki/Replication%20protein%20A1 | Replication protein A 70 kDa DNA-binding subunit is a protein that in humans is encoded by the RPA1 gene.
Interactions
Replication protein A1 has been shown to interact with:
BRCA2,
BLM,
MCM2,
MCM4,
MCM6,
MCM7,
MUTYH,
ORC2L,
ORC6L,
P53,
RPA2,
RPA3,
TIPIN,
TP53BP1, and
XPA.
See also
DNA-binding subunit
Replication protein A
Replication protein A2
Replication protein A3
Single-stranded binding protein
References
Further reading |
https://en.wikipedia.org/wiki/DJ-1 | Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene.
Structure
Gene
The gene PARK7, also known as DJ-1, encodes a protein of the peptidase C56 family. The human gene PARK7 has 8 exons and locates at chromosome band 1p36.23.
Protein
The human protein deglycase DJ-1 is 20 kDa in size and composed of 189 amino acids with seven β-strands and nine α-helices in total and is present as a dimer. It belongs to the peptidase C56 family of proteins.
The protein structures of human protein DJ-1, Escherichia coli chaperone Hsp31, YhbO, and YajL and an Archaea protease are evolutionarily conserved.
Function
Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity, thus functioning as a redox-sensitive chaperone and as a sensor for oxidative stress. Accordingly, DJ-1 apparently protects neurons against oxidative stress and cell death. In parallel, protein DJ-1 acts as a positive regulator of androgen receptor-dependent transcription. DJ-1 is expressed in both the neural retina and retinal pigment epithelium of mammals, where it exerts a neuroprotective role against oxidative stress under both physiological and pathological conditions.
Pyrroloquinoline quinone (PQQ) has been shown to reduce the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson's disease.
Functional DJ-1 protein has been shown to bind metal |
https://en.wikipedia.org/wiki/IGFBP5 | Insulin-like growth factor-binding protein 5 (IBF-5) is a protein that in humans is encoded by the IGFBP5 gene. An IGFBP5 gene was recently identified as being important for adaptation to varying water salinity in fish.
References
Further reading |
https://en.wikipedia.org/wiki/JUP | JUP may refer to:
JUP (gene), a gene on chromosome 17
Jamiat Ulema-e-Pakistan, a Political Party of Pakistan
Jupiter Fund Management, a Britispoolpur pplph fpliióund management Pl0
Juventud Uruguaya de Pie, a former Uruguayan far-right student organization
People with the name
Jup Weber (born 1950), Luxembourgian politician
See also
Jupp (disambiguation)
Jupe (disambiguation)
jup, ISO 639 code of the Hup language of the Amazon |
https://en.wikipedia.org/wiki/POLR2K | DNA-directed RNA polymerases I, II, and III subunit RPABC4 is a protein that in humans is encoded by the POLR2K gene.
This gene encodes one of the smallest subunits of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases.
Interactions
POLR2K has been shown to interact with POLR2C.
References
Further reading |
https://en.wikipedia.org/wiki/REL | The proto-oncogene c-Rel is a protein that in humans is encoded by the REL gene. The c-Rel protein is a member of the NF-κB family of transcription factors and contains a Rel homology domain (RHD) at its N-terminus and two C-terminal transactivation domains. c-Rel is a myeloid checkpoint protein that can be targeted for treating cancer. c-Rel has an important role in B-cell survival and proliferation. The REL gene is amplified or mutated in several human B-cell lymphomas, including diffuse large B-cell lymphoma and Hodgkin's lymphoma.
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Spastin | The human gene SPAST codes for the microtubule-severing protein of the same name, commonly known as spastin.
This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The encoded ATPase may be involved in the assembly or function of nuclear protein complexes. Two transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their full length sequences have not been determined. Mutations associated with this gene cause the most frequent form of autosomal dominant spastic paraplegia 4 (SPG4).
See also
Spastic paraplegia
Microtubule-associated protein
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia Type 4 |
https://en.wikipedia.org/wiki/YWHAH | 14-3-3 protein eta also referred to as 14-3-3η is a protein that in humans is encoded by the YWHAH gene.
Function
This gene product belongs to the 14-3-3 family of proteins that are normally intracellular in nature and help to mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat has been associated with early-onset schizophrenia.
Protein-protein interactions
YWHAH has been shown to interact with:
C-Raf,
CDC25B,
EPB41L3,
Glucocorticoid receptor,
KIF5B,
KLC3,
Phosphoinositide-dependent kinase-1,
RIMS1,
RIMS2,
TLX2,
TNFAIP3, and
ZFP36.
Externalization
14-3-3n is normally intracellular. Two main mechanisms resulting in the release of 14-3-3η into the extracellular environment have been reported:
exosomal mediated process; and
necroptosis;
14-3-3 proteins are components of small extracellular vesicles that are secreted by most, if not all cells. Tumor necrosis factor alpha stimulation of macrophages, but not IL-6, promotes the secretion of 14-3-3η into the extracellular space through a TNF alpha-dependent necroptotic mechanism.
Role in rheumatoid arthritis
A 2021 systematic literature review published by authors from the NHS Foundation Trust in the United Kingdom conclude the f |
https://en.wikipedia.org/wiki/HIST3H3 | Histone H3.1t is a protein that in humans is encoded by the HIST3H3 gene.
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is located separately from the other H3 genes that are in the histone gene cluster on chromosome 6p22-p21.3.
References
Further reading |
https://en.wikipedia.org/wiki/AXIN1 | Axin-1 is a protein that in humans is encoded by the AXIN1 gene.
Function
This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometrioid adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.
The AXIN proteins attract substantial interest in cancer research as AXIN1 and AXIN2 work synergistically to control pro-oncogenic β-catenin signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers.
Structure
The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved |
https://en.wikipedia.org/wiki/Caspase%206 | Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.
CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegeneration in Huntington's and Alzheimer's disease.
Function
This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene results in two transcript variants that encode different isoforms.
Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine interleukin-10 and cleaves the macrophage suppressing IRAK-M.
With respect to neurodegeneration, caspase-6 cleaves HTT in Huntington's and APP in Alzheimer's disease. Resulting in both cases in protein aggregation of the fragments.
Interactions
Caspase 6 ha |
https://en.wikipedia.org/wiki/CDX2 | Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The CDX2 protein is a homeobox transcription factor expressed in the nuclei of intestinal epithelial cells, playing an essential role in the development and function of the digestive system. CDX2 part of the ParaHox gene cluster, a group of three highly conserved developmental genes present in most vertebrate species. Together with CDX1 and CDX4, CDX2 is one of three caudal-related genes in the human genome.
Function
In common with the two other Cdx genes, CDX2 regulates several essential processes in the development and function of the lower gastrointestinal tract (from the duodenum to the anus) in vertebrates. In vertebrate embryonic development, CDX2 becomes active in endodermal cells that are posterior to the developing stomach. These cells eventually form the intestinal epithelium. The activity of CDX2 at this stage is essential for the correct formation of the intestine and the anus. CDX2 is also required for the development of the placenta.
Later in development, CDX2 is expressed in intestinal epithelial stem cells, which are cells that continuously differentiate into the cells that form the intestinal lining. This differentiation is dependent on CDX2, as illustrated by experiments where the expression of this gene was knocked-out or overexpressed in mice. Heterozygous CDX2 knock-outs have intestinal lesions caused by the differentiation of intestinal cells into gastric epithelium; this |
https://en.wikipedia.org/wiki/KSTB | KSTB (101.5 FM) was a radio station broadcasting a country music format. Licensed to serve the community of Crystal Beach, Texas, United States, it served the Houston area during its time on the air. The station was owned and operated by Cumulus Media.
Shutdown
On September 13, 2008, the transmitter facility and all of the transmitting equipment were "washed away" by Hurricane Ike. After Hurricane Ike, Cumulus had filed for permission for the station to cease operations and stated that it had no specific plans on whether it will attempt to rebuild the station given the scope of the disaster and the poor economic conditions, according to the FCC filing. The FCC accepted the filing, but did not approve the request as of January 2009. The FCC's standard position is that if a licensed facility remains silent for a year, the license expires as a matter of law, although some exceptions are made.
Prior to its country format, from 2001 to 2009, KSTB played an adult contemporary format under the brand "Star 101.5" with the slogan "The Star Of The Bay." The station was owned by Galtex Broadcasting. While the transmitter was located in Crystal Beach, the business offices and studios were located in Webster, Texas at 711 W. Bay Area Blvd. - in the Bay Area of Houston and Southern Harris County, about 25 miles south of downtown Houston.
Before KSTB broadcast on the 101.5 frequency, its dial position was 104.9 FM with the call sign KRTX, and was licensed to Galveston. At that time the s |
https://en.wikipedia.org/wiki/Myeloma%20protein | A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myeloma or Monoclonal gammopathy of undetermined significance. Other terms for such a protein are monoclonal protein, M protein, M component, M spike, spike protein, or paraprotein. This proliferation of the myeloma protein has several deleterious effects on the body, including impaired immune function, abnormally high blood viscosity ("thickness" of the blood), and kidney damage.
History
The concept and the term paraprotein were introduced by the Berlin pathologist Dr Kurt Apitz in 1940, then the senior physician of the pathological institute at the Charité hospital.
Paraproteins allowed the detailed study of immunoglobulins, which eventually led to the production of monoclonal antibodies in 1975.
Cause
Myeloma is a malignancy of plasma cells. Plasma cells produce immunoglobulins, which are commonly called antibodies. There are thousands of different antibodies, each consisting of pairs of heavy and light chains. Antibodies are typically grouped into five classes: IgA, IgD, IgE, IgG, and IgM. When someone has myeloma, a malignant clone, a rogue plasma cell, reproduces in an uncontrolled fashion, resulting in overproduction of the specific antibody the original cell was generated to produce. Each type of antibody has a different n |
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