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https://en.wikipedia.org/wiki/PTPN2 | Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene.
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation.
Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Three alternatively spliced variants of this gene, which encode isoforms differing at their extreme C-termini, have been described.
The different C-termini are thought to determine the substrate specificity, as well as the cellular localization of the isoforms. Two highly related but distinctly processed pseudogenes that localize to distinct chromosomes have been reported.
References
Further reading |
https://en.wikipedia.org/wiki/SAT1%20%28gene%29 | Diamine acetyltransferase 1 is an enzyme that in humans is encoded by the SAT1 gene found on the X chromosome.
Function
Spermidine/spermine N(1)-acetyltransferase (SPD/SPM acetyltransferase) is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the N(1)-acetylation of spermidine and spermine and, by the successive activity of polyamine oxidase, spermine can be converted to spermidine and spermidine to putrescine. The SAT1 gene is used to help regulate polyamine levels inside the cell by regulating their transport in and out of the cell. SAT1 is also involved in the first step to synthesize N-acetylputrescine from putrescine. PMF1 and NRF2 work together to transcript the SAT1 gene.
Structure
The SAT1 gene is 3,069 base pairs long. There are 171 amino acids and its molecular mass is 20024 Da Daltons). In 1992 at The Johns Hopkins University School of Medicine, Lei Xiao and several others cloned over 4000 base pairs of the region containing the coding sequence of the SAT1 gene also referred to as SSAT-1, SSAT, SAT, KFSD, DC21, KFSDX gene. This gene is located on the X chromosome in the region Xp22.1. The primer extension analysis indicated that the transcription started 179 bases upstream from the translational start site. Furthermore, they determined that it appeared to be controlled by a "TATA-less" promoter. Normally, there would be a TATA box where RNA polymerase II would be involved in assisting with initiation by properly posi |
https://en.wikipedia.org/wiki/Small%20nuclear%20ribonucleoprotein%20polypeptide%20N | Small nuclear ribonucleoprotein-associated protein N is a protein that in humans is encoded by the SNRPN gene.
The protein encoded by this gene is one polypeptide of a small nuclear ribonucleoprotein complex and belongs to the snRNP SMB/SMN family. The protein plays a role in pre-mRNA processing, possibly tissue-specific alternative splicing events. Although individual snRNPs are believed to recognize specific nucleic acid sequences through RNA-RNA base pairing, the specific role of this family member is unknown. The protein arises from a bicistronic transcript that also encodes a protein identified as the SNRPN upstream reading frame (SNURF). Multiple transcription initiation sites have been identified and extensive alternative splicing occurs in the 5' untranslated region. Additional splice variants have been described but sequences for the complete transcripts have not been determined. The 5' UTR of this gene has been identified as an imprinting center. Alternative splicing or deletion caused by a translocation event in this paternally-expressed region is responsible for Prader-Willi syndrome due to parental imprint switch failure.
SNRPN-methylation is used to detect uniparental disomy of chromosome 15. After fluorescent-in-situ-hybridization has confirmed the presence of either SNRPN or UBE3A (a neighboring gene that is also imprinted), the methylation test (of SNRPN) can reveal whether the patient has uniparental disomy. SNRPN is maternally methylated (silenced). UBE |
https://en.wikipedia.org/wiki/ST14 | Suppressor of tumorigenicity 14 protein, also known as matriptase, is a protein that in humans is encoded by the ST14 gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.
Function
Matriptase is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is found to be activated by sphingosine-1-phosphate. This protease has been shown to cleave and activate hepatocyte growth factor/scatter factor, and urokinase plasminogen activator, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors.
Matriptase is a type II transmembrane serine protease expressed in most human epithelia, where it is coexpressed with its cognate transmembrane inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. Activation of the matriptase zymogen requires sequential N-terminal cleavage, activation site autocleavage, and transient association with HAI-1. Matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth. Matriptase is an 80- to 90-kDa cell surface glycoprotein with a complex modular structure that is common to all matriptases.
Clinical significance
The expression of this protease h |
https://en.wikipedia.org/wiki/TP53BP2 | Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
Nomenclature
ASPP2 (amino acid residues 600 –1128) was initially identified as 53BP2 (p53-binding protein 2) in a yeast two hybrid screen using p53 as the bait. Another yeast two hybrid screening in which Bcl-2 was used as the bait gave rise to the discovery of another fragment of ASPP2 (residues 123-1128) and it was called Bbp. The full length ASPP2 (1128 amino acids) was identified later.
Function
ASPP2 plays a central role in regulation of apoptosis and cell growth via its interactions. ASPP2 regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. ASPP2 binds to wild-type p53 but fails to bind to mutant p53, suggesting that ASPP2 may be involved in the ability of wild-type p53 to suppress transformation. ASPP2 induces apoptosis but no cell cycle arrest.
Structure
ASPP2 contains several structural and functional domains. Its N-terminus (residues 1–83) has the structure of a β-grasp ubiquitin-like fold. It is followed by a predicted α-helical domain located between aa 123 and 323. and a proline-rich (ASPP2 Pro) domain between aa 674 and 902. The C-terminal part of ASPP2 contains four ankyrin repeats and an SH3 dom |
https://en.wikipedia.org/wiki/Nucleoporin%20214 | Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.
Function
The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene is a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is localized to the cytoplasmic face of the nuclear pore complex where it is required for proper cell cycle progression and nucleocytoplasmic transport. The 3' portion of this gene forms a fusion gene with the DEK gene on chromosome 6 in a t(6,9) translocation associated with acute myeloid leukemia and myelodysplastic syndrome.
Structure
The structure of the N-terminal domain of Nup214 reveals a sevenbladed beta-propeller fold followed by a 30-residue C-terminal extended peptide segment (CTE). The CTE folds back onto the beta propeller and binds to its bottom face. The structure of the Nup214 NTD bound to the helicase Ddx19 in its ADP-bound state reveals the molecular basis for the interaction between the two proteins. A conserved residue of Ddx19 is shown to be crucial for complex formation in vitro and in vivo. Strikingly, the interaction surfaces exhibit strongly opposing surface potentials, with the helicase surface being positively and the Nup214 surface being negatively charged. Ddx19 is shown to bind RNA o |
https://en.wikipedia.org/wiki/ARHGEF7 | Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.
ARHGEF7 is commonly known as the p21-activated protein kinase exchange factor beta (beta-PIX or βPIX), because it was identified by binding to p21-activated kinase (PAK) and also contains a guanine nucleotide exchange factor domain.
Domains and functions
βPIX is a multidomain protein that functions both as a signaling scaffold protein and as an enzyme. βPIX shares this domain structure and signaling function with the highly similar ARHGEF6/αPIX protein.
βPIX undergoes extensive alternative splicing to generate multiple variant proteins containing or lacking particular protein domains. Adult forms all lack the amino terminal CH domain, and the two major adult variants have alternate carboxyl terminal region (termed β1 and β2): β1 forms contain the coiled-coil trimerization domain and the PDZ-target motif for binding to PDZ proteins (see below), while β2 forms lack both domains and their corresponding functions.
βPIX contains a central DH/PH RhoGEF domain that functions as a guanine nucleotide exchange factor (GEF) for small GTPases of the Rho family, and specifically Rac and Cdc42. Like other GEFs, βPIX can promote both release of GDP from an inactive small GTP-binding protein and binding of GTP to promote its activation.
Signaling scaffolds bind to specific partners to promote efficient signal transduction by arranging sequential elements of a pathway near each other to |
https://en.wikipedia.org/wiki/DNA%20polymerase%20lambda | DNA polymerase lambda, also known as Pol λ, is an enzyme found in all eukaryotes. In humans, it is encoded by the POLL gene.
Function
Pol λ is a member of the X family of DNA polymerases. It is thought to resynthesize missing nucleotides during non-homologous end joining (NHEJ), a pathway of DNA double-strand break (DSB) repair. NHEJ is the main pathway in higher eukaryotes for repair of DNA DSBs. Chromosomal DSBs are the most severe type of DNA damage. During NHEJ, duplexes generated by the alignment of broken DNA ends usually contain small gaps that need to be filled in by a DNA polymerase. DNA polymerase lambda can perform this function.
The crystal structure of pol λ shows that, unlike the DNA polymerases that catalyze DNA replication, pol λ makes extensive contacts with the 5' phosphate of the downstream DNA strand. This allows the polymerase to stabilize the two ends of a double-strand break and explains how pol λ is uniquely suited for a role in non-homologous end joining.
In addition to NHEJ, pol λ can also participate in base excision repair (BER), where it provides backup activity in the absence of Pol β. BER is the major pathway for repair of small base damages resulting from alkylation, oxidation, depurination/depyrimidination, and deamination of DNA.
Besides its catalytic polymerase domain, pol λ has an 8 kDa domain and a BRCT domain. The 8 kDa domain has lyase activity that can remove a 5' deoxyribosephosphate group from the end of a strand break. |
https://en.wikipedia.org/wiki/HtrA%20serine%20peptidase%202 | Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This protein is involved in caspase-dependent apoptosis and in Parkinson's disease.
Structure
Gene
The gene HTRA2 encodes a serine protease. The human gene has 8 exons and locates at chromosome band 2p12.
Protein
Protein HtrA2, also known as Omi, is a mitochondrially-located serine protease. The human protein Serine protease HTRA2, mitochondrial is 49kDa in size and composed of 458 amino acids. The peptide fragment of 1-31 amino acid is the mitochondrial transition sequence, fragment 32-133 amino acid is propertied, and 134-458 is the mature protein Serine protease HTRA2, mitochondrial, and its theoretical pI of this protein is 6.12. HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and a carboxy-terminal PDZ domain, which is characteristic of the HtrA family. The PDZ domain preferentially binds C-terminus of the protein substrate and modulate the proteolytic activity of the trypsin-like protease domain.
Function
The high-temperature requirement (HtrA) family are conserved evolutionarily and these oligomeric serine proteases has been classified in family S1B of the PA protease clan in the MEROPS protease database. The protease activity of the HtrA member HtrA2/Omi is required for mitochondrial homeostasis in mice and humans and inactivating mutat |
https://en.wikipedia.org/wiki/Argininosuccinate%20synthetase%201 | Argininosuccinate synthetase is an enzyme that in humans is encoded by the ASS1 gene.
The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Two transcript variants encoding the same protein have been found for this gene.
Clinical significance
Mutations in the chromosome 9 copy of ASS cause citrullinemia.
40% to 90% of bladder cancers are deficient in argininosuccinate synthetase.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Urea Cycle Disorders Overview
GeneReviews/NCBI/NIH/UW entry on Argininosuccinate Synthetase Deficiency; ASS Deficiency; Argininosuccinic Acid Synthetase Deficiency; CTLN1; Citrullinemia, Classic |
https://en.wikipedia.org/wiki/CYLD%20%28gene%29 | The CYLD lysine 63 deubiquitinase gene, also termed the CYLD gene, CYLD is an evolutionary ancient gene found to be present as far back on the evolutionary scale as in sponges. In humans, this gene is located in band 12.1 on the long (or "q") arm of chromosome 16 and is known to code (i.e. direct the production of) multiple proteins through the process of alternative splicing.
The CYLD gene in known to code for a cytoplasmic protein, termed CYLD lysine 63 deubiquitinase (here termed CYLD protein), which has three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains (areas or the protein controlling critical functions). CYLD protein is a deubiquitinating enzyme, i.e. a protease that removes ubiquitin from certain proteins and thereby regulates these proteins' activities. CYLD protein removes ubiquitin from proteins involved in regulating the NF-κB, Wnt, notch, TGF-β, and JNK cell signaling pathways; these pathways normally act to regulate hair formation, cell growth, cell survival, inflammatory responses, and/or tumor development.
The CYLD gene is classified as a tumor suppressor gene, i.e. a gene that regulates cell growth and when inactivated by a mutation leads to uncontrolled cell growth and the formation of tumors. Inactivating mutations in this gene occur in essentially all cases of the CYLD cutaneous syndrome, a hereditary disorder in which individuals develop multiple skin tumors. The CYLD cutaneous syndrome includes three somewhat different forms of t |
https://en.wikipedia.org/wiki/FSHB | Follitropin subunit beta also known as follicle-stimulating hormone beta subunit (FSH-B) is a protein that in humans is encoded by the FSHB gene. Alternative splicing results in two transcript variants encoding the same protein.
Function
The pituitary glycoprotein hormone family includes follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid-stimulating hormone. All of these glycoproteins consist of an identical alpha subunit and a hormone-specific beta subunit. This gene encodes the beta subunit of follicle-stimulating hormone. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production.
The FSHB gene in human DNA encodes the follicle-stimulating hormone subunit beta protein (FSH-B), or Follitropin Beta. More specifically, the FSHB gene encodes for the beta subunit of follicle-stimulating hormone (FSH). Therefore, proper transcription of FSHB allows for the proper production of FSH. FSH is a peptide hormone the pituitary gland produces that is involved with the reproductive system. FSH promotes follicular oocyte (egg) production, growth, and maturation and helps control a female's menstrual cycle. Additionally, FSH is involved in the male reproductive system by stimulating spermatogenesis (maturation of sperm cells) and initiating puberty. Studies show that variations in the FSHB gene can contribute to the likelihood of a woman becoming pregnant with fraternal, or dizygotic, twins. This is becaus |
https://en.wikipedia.org/wiki/IFNA2 | Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.
Protein family
Human interferon alpha-2 (IFNα2) is a cytokine belonging to the family of type I IFNs. IFNα2 is a protein secreted by cells infected by a virus and acting on other cells to inhibit viral infection. The first description of IFNs as a cellular agent interfering with viral replication was made by Alick Isaacs and Jean Lindenmann in 1957. The history of this finding was recently reviewed. There are 3 types of IFNs: Interferon type I, Interferon type II and Interferon type III. The type II IFN, also called IFNγ, is produced by specific cells of the immune system. Unlike type I and type III IFNs, IFNγ has only a modest role in directly restricting viral infections. Type I and type III IFNs act similarly. However, the action of type III IFNs, also known as IFNλ, is limited to epithelial cells while type I IFNs act on all body's cells.
Type I IFNs form a family of several proteins: in humans, there are 13 α subtypes, 1 β subtype, 1 ω subtype and other less studied subtypes (κ and ε). IFNα2 was the first subtype to be characterized in the early eighties. As a result, IFNα2 was widely used in basic research to elucidate biological activities, structure and mechanism of action of type I IFNs. IFNα2 was also the first IFN to be produced by the pharmaceutical industry for use as a drug. Thereby, IFNα2 is the best known type I IFN subtype. The properties of IFNα2 are widely shared by the other t |
https://en.wikipedia.org/wiki/MARCKS | Myristoylated alanine-rich C-kinase substrate is a protein that in humans is encoded by the MARCKS gene.
It plays important roles in cell shape, cell motility, secretion, transmembrane transport, regulation of the cell cycle, and neural development. Recently, MARCKS has been implicated in the exocytosis of a number of vesicles and granules such as mucin and chromaffin.
It is also the name of a protein family, of which MARCKS is the most studied member. They are intrinsically disordered proteins, with an acidic pH, with high proportions of alanine, glycine, proline, and glutamic acid. They are membrane-bound through a lipid anchor at the N-terminus, and a polybasic domain in the middle. They are regulated by Ca2+/calmodulin and protein kinase C. In their unphosphorylated form, they bind to actin filaments, causing them to crosslink, and sequester acidic membrane phospholipids such as PIP2.
The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis.
Interactions
MARCKS has been shown to interact with TOB1 and with NMT2.
References
Further reading |
https://en.wikipedia.org/wiki/FOXO4 | Forkhead box protein O4 is a protein that in humans is encoded by the FOXO4 gene.
Structure and function
FOXO4 is a member of the forkhead family transcription factors O subclass, which is characterized by a winged helix domain used for DNA binding. There are 4 members of the FOXO family, including FOXO1, FOXO3, and FOXO6. Their activity is modified by many post translational activities, such as phosphorylation, ubiquitination, and acetylation. Depending on this modified state, FOXO4 binding affinity for DNA is altered, allowing for FOXO4 to regulate many cellular pathways including oxidative stress signaling, longevity, insulin signaling, cell cycle progression, and apoptosis. Two of the main upstream regulators of FOXO4 activity are phosphoinositide 3- kinase (PI3K) and serine/threonine kinase AKT/PKB. Both PI3K and AKT modify FOXO4 and prevent it from translocating to the nucleus, effectively preventing the transcription of the downstream FOXO targets.
Clinical significance
Associations with longevity
FOXO transcription factors have been shown to be the down downstream effector molecules of insulin-like growth factor (IGF) signaling pathway. In the absence of insulin, PI3K is inactive, so the FOXO homolog daf-16 is able to translocate to the nucleus and turn on many genetic pathways associated with longevity in the roundworm Caenorhabditis elegans. FOXO's activation of these pathways produces an increase in lifespan for worms, flies, mice; similar variants of FOXO3a |
https://en.wikipedia.org/wiki/PLA2G1B | Phospholipase A2, group 1B is an enzyme that in humans is encoded by the PLA2G1B gene.
Function
Phospholipase A2 (EC 3.1.1.4) catalyzes the release of fatty acids from glycero-3-phosphocholines. The best known varieties are the digestive enzymes secreted as zymogens by the pancreas of mammals as well as fish. Sequences of pancreatic PLA2 enzymes from a variety of mammals have been reported. One striking feature of these enzymes is their close homology to venom phospholipases of snakes. Other forms of PLA2 have been isolated from brain, liver, lung, spleen, intestine, macrophages, leukocytes, erythrocytes, inflammatory exudates, chondrocytes, and platelets (Seilhamer et al., 1986) .
References
Further reading |
https://en.wikipedia.org/wiki/Radixin | Radixin is a protein that in humans is encoded by the RDX gene.
Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses.
Interactions
Radixin has been shown to interact with GNA13.
See also
ERM protein family
References
Further reading |
https://en.wikipedia.org/wiki/RFC1 | Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.
Function
The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replication factor C is a DNA-dependent ATPase that is required for eukaryotic DNA replication and repair. The protein acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It also may have a role in telomere stability.
Interactions
RFC1 has been shown to interact with:
BRD4,
HDAC1,
PCNA,
RELA and
RFC3.
Clinical relevance
Biallelic intronic repeat expansions (a series of repeating nucleotide sequences) in the replication factor C subunit 1 (RFC1) gene causes cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Within the poly(A) tail of an AluSx3 element in RFC1, there are eleven repeats of the pentanucleotide "AAAAG". Repeat expansion and polymorphic configuration are observed in part of the population, with increased number of repeats associated to alternative "AAAGG", "AAGGG" and "ACAGG" pentanucleotides. In particular, biallelic "AAGGG" and "ACAGG" repeat expansion have disproportionately been observed in patients with CANVAS. Biallelic "AAGGG" repeat expansion is also reported in a high number of sporadic cases of late-onset ataxia, isolate sensory neuropathy and, less frequently, isolate cerebellar ataxia. Due to a diagnostic overlap |
https://en.wikipedia.org/wiki/RPS6KA2 | Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.
This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine and threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
Interactions
RPS6KA2 has been shown to interact with MAPK3 and MAPK1.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/S100A6 | S100 calcium-binding protein A6 (S100A6) is a protein that in humans is encoded by the S100A6 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 stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma.
Interactions
S100A6 has been shown to interact with S100B and SUGT1.
Pathology
S100A6 to be reported as possible diagnostic marker of papillary thyroid carcinoma.
References
Further reading
S100 proteins |
https://en.wikipedia.org/wiki/Semenogelin%20I | Semenogelin-1 is a protein that in humans is encoded by the SEMG1 gene.
The protein encoded by this gene is the predominant protein in semen. The encoded secreted protein is involved in the formation of a gel matrix that encases ejaculated spermatozoa. The prostate-specific antigen (PSA) protease processes this protein into smaller peptides, with each possibly having a separate function. The proteolysis process breaks down the gel matrix and allows the spermatozoa to move more freely. Two transcript variants encoding different isoforms have been found for this gene.
See also
Semenogelin
References
Further reading |
https://en.wikipedia.org/wiki/Secreted%20frizzled-related%20protein%201 | Secreted frizzled-related protein 1, also known as SFRP1, is a protein which in humans is encoded by the SFRP1 gene.
Function
Secreted frizzled-related protein 1 (SFRP1) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. SFRP1 and SFRP5 may be involved in determining the polarity of photoreceptor cells in the retina. SFRP1 is expressed in several human tissues, with the highest levels in the heart.
The Secreted frizzled-related protein (SFRP) family consists of five secreted glycoproteins in humans (SFRP1, SFRP2, SFRP3, SFRP4, SFRP5) that act as extracellular signaling ligands. Each SFRP is ~300 amino acids in length and contains a cysteine-rich domain (CRD) that shares 30-50% sequence homology with the CRD of Frizzled (Fz) receptors. SFRPs are able to bind Wnt proteins and Fz receptors in the extracellular compartment. The interaction between SFRPs and Wnt proteins prevents the latter from binding the Fz receptors. SFRPs are also able to downregulate Wnt signaling by the formation of an inhibitory complex with the Frizzled receptors. The Wnt pathway plays a key role in embryonic development, cell differentiation and cell proliferation. It has been shown that the deregulation of this critical developmental pathway occurs in several human tumor entities.
SFRP1 is a 35 kDa prototypical member of the SFRP family. It acts as a biphasic mod |
https://en.wikipedia.org/wiki/PMEL%20%28gene%29 | Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
Structure and function
PMEL is a 100 kDa, 661 amino acids long type I transmembrane glycoprotein that is expressed primarily in melanosomes, which are the melanin-producing organelles in melanocytes of pigment cells of the skin and eye, and in most malignant melanomas.
This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization (Eisenberg) . The transmembrane form of PMEL is modified in the secretory pathway by elaboration of N-linked oligosaccharides and addition and modification of O-linked oligosaccharides. It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments. Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure. PMEL cleavage is mediated by several proteases including a proprotein convertase of the furin family, a "sheddase" that might include members of the a disintegrin and metalloproteinase (ADAM) family, and additional proteases in melanosomes or their precursors. After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is |
https://en.wikipedia.org/wiki/Structure%20specific%20recognition%20protein%201 | FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.
Function
The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63.
Interactions
Structure specific recognition protein 1 has been shown to interact with NEK9.
SSRP1 further interacts with transcriptional activator p63. SSRP1 enhances the activity of full-length p63, but it has no effect on the N-terminus-deleted p63 (DeltaN-p63) variant.
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Peroxiredoxin%202 | Peroxiredoxin-2 is a protein that in humans is encoded by the PRDX2 gene.
PRDX2 encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. The crystal structure of this protein has been resolved to 0.27 nm (= 2.7 angstroms). Transcript variants encoding distinct isoforms have been identified for this gene.
References
Further reading |
https://en.wikipedia.org/wiki/Trefoil%20factor%202 | Trefoil factor 2 is a protein that in humans is encoded by the TFF2 gene.
Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. The encoded protein inhibits gastric acid secretion. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.
Glycan binding
All human trefoil factors are lectins that interact specifically with the disaccharide GlcNAc-α-1,4-Gal. This disaccharide is an unusual glycotope that is only known to exist on the large, heavily glycosylated, mucins in the mucosa. By cross-linking mucins through the bivalent binding of this glycotope, the trefoil factors are then able to reversible modulate the thickness and viscosity of the mucus.
References
Further reading |
https://en.wikipedia.org/wiki/USF2 | Upstream stimulatory factor 2 is a protein that in humans is encoded by the USF2 gene.
Function
This gene encodes a member of the basic helix-loop-helix leucine zipper family, and can function as a cellular transcription factor. The encoded protein can activate transcription through Pyridine-rich initiator (Inr) elements and E-box motifs. Two transcript variants encoding distinct isoforms have been identified for this gene.
Interactions
USF2 has been shown to interact with USF1 (human gene), PPRC1 and BRCA1.
Regulation
The USF2 gene is repressed by the microRNA miR-10a.
References
Further reading
External links |
https://en.wikipedia.org/wiki/Protein%20BTG2 | Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the BTG2 gene (B-cell translocation gene 2) and in other mammals by the homologous Btg2 gene. This protein controls cell cycle progression and proneural genes expression by acting as a transcription coregulator that enhances or inhibits the activity of transcription factors.
The protein BTG2 is the human homolog of the PC3 (pheochromocytoma cell 3) protein in rat and of the Tis21 (tetradecanoyl phorbol acetate-inducible sequence 21) protein in mouse. Tis21 had been originally isolated as a sequence induced by TPA in mouse fibroblasts, whereas PC3 was originally isolated as sequence induced at the beginning of neuron differentiation; BTG2 was then isolated in human cells as sequence induced by p53 and DNA damage.
The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2). This family has structurally related proteins that appear to have antiproliferative properties. In particular, the BTG2 protein has been shown to negatively control a cell cycle checkpoint at the G1 to S phase transition in fibroblasts and neuronal cells by direct inhibition of the activity of cyclin D1 promoter.
Regulator of neuron differentiation
A number of studies in v |
https://en.wikipedia.org/wiki/GIPC1 | GIPC PDZ domain containing family, member 1 (GIPC1) is a protein that in humans is encoded by the GIPC1 gene. GIPC was originally identified as it binds specifically to the C terminus of RGS-GAIP, a protein involved in the regulation of G protein signaling. GIPC is an acronym for "GAIP Interacting Protein C-terminus". RGS proteins are "Regulators of G protein Signaling" and RGS-GAIP is a "GTPase Activator protein for Gαi/Gαq", which are two major subtypes of Gα proteins. The human GIPC1 molecule is 333 amino acids or about 36 kDa in molecular size and consists of a central PDZ domain, a compact protein module which mediates specific protein-protein interactions. The RGS-GAIP protein interacts with this domain and many other proteins interact here or at other parts of the GIPC1 molecule. As a result, GIPC1 was independently discovered by several other groups and has a variety of alternate names, including synectin, C19orf3, RGS19IP1 and others. The GIPC1 gene family in mammals consisting of three members, so the first discovered, originally named GIPC, is now generally called GIPC1, with the other two being named GIPC2 and GIPC3. The three human proteins are about 60% identical in protein sequence. GIPC1 has been shown to interact with a variety of other receptor and cytoskeletal proteins including the GLUT1 receptor, ACTN1, KIF1B, MYO6, PLEKHG5, SDC4/syndecan-4, SEMA4C/semaphorin-4 and HTLV-I Tax. The general function of GIPC family proteins therefore appears to be mediating |
https://en.wikipedia.org/wiki/PLCB1 | 1-Phosphatidylinositol-4,5-bisphosphate phospholipase beta-1 is an enzyme that in humans is encoded by the PLCB1 gene.
Function
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.
Interactions
PLCB1 has been shown to interact with TRPM7.
Pathology
Homozygous PLCB1 deletion is associated with malignant migrating partial seizures in infancy.
References
Further reading
EC 3.1.4 |
https://en.wikipedia.org/wiki/WNK1 | WNK (lysine deficient protein kinase 1), also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).
Structure
The WNK1 protein is composed of 2382 amino acids (molecular weight 230 kDa). The protein contains a kinase domain located within its short N-terminaldomain and a long C-terminal tail. The kinase domain has some similarity to the MEKK protein kinase family. As a member of the WNK family, the kinase's catalytic lysine residue is uniquely located in beta strand 2 of the glycine loop. In order to have kinase activity, WNK1 must autophosphorylate the serine 382 residue found in its activation loop. Further, phosphorylation at another site (Ser378) increases WNK1 activity. An autoinhibitory domain is located within the C-terminal domain along with a HQ domain that is needed for WNK1 interactions with other WNKs. The interactions between WNKs play an important role in function; WNK1 mut |
https://en.wikipedia.org/wiki/ABL2 | Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene.
Function
ABL2 is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins includes the tyrosine kinase domains and extends amino-terminal to include the SH2 and SH3 domains. ABL2 is expressed in both normal and tumor cells. The expression of ABL2 gene is higher in KRAS mutant non-small cell lung cancer. The ABL2 gene product is expressed as two variants bearing different amino termini, both approximately 12-kb in length.
Interactions
ABL2 has been shown to interact with three proteins: Abl gene, catalase, and SORBS2. The protein Abl gene is also known as abelson murine leukemia viral oncogene homolog 1 and is a protein that is encoded by the human ABL1 gene. Catalase is a common enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen. SORBS2 is also known as Sorbin and SH3 domain-containing protein 2 and is a protein encoded by the SORBS2 gene in humans.
References
Further reading
External links
ABL2 Info with links in the Cell Migration Gateway
Tyrosine kinases
Oncogenes |
https://en.wikipedia.org/wiki/CHRNB2 | Neuronal acetylcholine receptor subunit beta-2 is a protein that in humans is encoded by the CHRNB2 gene.
Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy.
It has been discovered that suppression, rather than stimulation, of B2-containing nAChR currents yields an antidepressant effect. This is believed to explain the significantly increased prevalence of cigarette smoking in depressed individuals and the profound rise in depressive symptoms during abstinence.
Interactive pathway map
See also
Nicotinic acetylcholine receptor
References
Further reading
External links
Ion channels
Nicotinic acetylcholine receptors |
https://en.wikipedia.org/wiki/DFFB | DFFB may refer to:
Deutsche Film- und Fernsehakademie Berlin
A human gene that encodes the caspase-activated DNase protein |
https://en.wikipedia.org/wiki/ERG%20%28gene%29 | ERG (ETS-related gene) is an oncogene. ERG is a member of the ETS (erythroblast transformation-specific) family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.
Function
Transcriptional regulator ERG is a nuclear protein that binds purine-rich sequences of DNA. Transcriptional regulator ERG is required for platelet adhesion to the subendothelium and regulates hematopoiesis. It has a DNA binding domain and a PNT (pointed) domain. ERG is expressed at higher levels in early myelocytes than in mature lymphocytes (types of white blood cells). Therefore, ERG may act as a regulator of differentiation of early hematopoietic cells.
The Mld2 mutation, generated through an ENU mutagenesis screen, was the first non-functional allele of Erg. Homozygous Mld2 is embryonic lethal at day 13.5. Adult mice heterozygous for the Mld2 mutation have hematopoietic stem cell defects. This means that when the ERG gene was not actively transcribed and the ERG protein produced, a mouse's hematopoietic cells were unable to function properly. Since ERG is important to the ability of the hematopoietic cells to function and self-renew, there may be applications in using blood stem cells for tissue repair, transplantation and other therapeutic applications.
Cancer
This gene can be classified a |
https://en.wikipedia.org/wiki/EXT2%20%28gene%29 | Exostosin glycosyltransferase-2 is a protein that in humans is encoded by the EXT2 gene.
This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of Hereditary Multiple Exostoses (HME).
Gene location
The EXT2 gene is located on chromosome 11 in the human genome, its location is on the p arm of this chromosome. The p arm of a chromosome is the shorter arm of a chromosome.
Interactions
Included in the EXT family are EXT2, EXT1, EXTL1, EXTL2, and EXTL3. The proteins formed by these genes work together to form and extend heparan sulfate chains. Heparan sulfate chains are proteoglycans present in the extracellular matrix of most tissue types. There is a lot about its function that is not entirely understood, however it is known that they have an important role for bone and cartilage formation. Cartilage is located at the growth plates of long bones and is placed in a specific pattern before it is later ossified into bone when it grows further away from the growth plate. New cartilage in a growing bone is placed through signaling proteins which bind to the heparan sulfate chains.
EXT2 (protein) has also been shown to interact with TRAP1, a heat shock protein. Heat shock proteins will bind to specific proteins to help them keep their shape when the cell is stressed. TRAP1 has been found to bind to a region (in the c-terminal end) of EXT1 and EXT2 proteins to help it ke |
https://en.wikipedia.org/wiki/FANCG | Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.
Function
FANCG, involved in Fanconi anemia, confers resistance to both hygromycin B and mitomycin C. FANCG contains a 5-prime GC-rich untranslated region characteristic of housekeeping genes. The putative 622-amino acid protein has a leucine-zipper motif at its N-terminus. Fanconi anemia is an autosomal recessive disorder with diverse clinical symptoms, including developmental anomalies, bone marrow failure, and early occurrence of malignancies. A minimum of 8 FA genes have been identified. The FANCG gene is responsible for complementation group G.
The clinical phenotype of all Fanconi anemia (FA) complementation groups is similar. This phenotype is characterized by progressive bone marrow failure, cancer proneness and typical birth defects. The main cellular phenotype is hypersensitivity to DNA damage, particularly inter-strand DNA crosslinks. The FA proteins interact through a multiprotein pathway. DNA interstrand crosslinks are highly deleterious damages that are repaired by homologous recombination involving coordination of FA proteins and breast cancer susceptibility gene 1 (BRCA1), but the exact biochemical roles of these proteins is currently unclear.
A nuclear complex containing FANCG (as well as FANCA, FANCB, FANCC, FANCE, FANCF, FANCL and FANCM) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform. In normal, non-mutant, cells FANCD |
https://en.wikipedia.org/wiki/Folate%20receptor%201 | Folate receptor 1 (Folate receptor alpha, FOLR1) is a protein that in humans is encoded by the FOLR1 gene.
The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this family have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells.
Functions
This receptor is responsible for binding to folic acid and its derivatives, which becomes crucial during fetal development. By adding folate supplementation during pregnancy, neural tube defects in the fetus are prevented. Folate derivatives are necessary for important metabolic processes such as DNA, protein and lipid methylation. More importantly, folate plays a major role in DNA replication and cell division, which are common characteristics of rapid growth. Even though it is unclear how folate affects neural tube formation, scientists are certain that without appropriate folate levels, neural tube defects can develop through human and mice studies. Neural tube defects refer to the improper development of the neural tube by not being sealed correctly. This results in exencephaly or spina bifida, both nervous system abnormalities.
This gene is composed of 7 exons; exons 1 through 4 encode the 5' UTR and exons 4 through 7 encode the open reading frame. Due to the presence of 2 promoters, multiple transcription start sites, and alternative splicing of exons, several transcript variants are derived |
https://en.wikipedia.org/wiki/RNA-binding%20protein%20FUS | RNA-binding protein FUS/TLS (FUsed in Sarcoma/Translocated in LipoSarcoma), also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the FUS gene.
Discovery
FUS/TLS was initially identified as a fusion protein (FUS-CHOP) produced as a result of chromosomal translocations in human cancers, especially liposarcomas. In these instances, the promoter and N-terminal part of FUS/TLS is translocated to the C-terminal domain of various DNA-binding transcription factors (e.g. CHOP) conferring a strong transcriptional activation domain onto the fusion proteins.
FUS/TLS was independently identified as the hnRNP P2 protein, a subunit of a complex involved in the maturation of pre-mRNA.
Structure
FUS/TLS is a member of the FET protein family that also includes the EWS protein, the TATA-binding protein TBP-associated factor TAFII68/TAF15, and the Drosophila cabeza/SARF protein.
FUS/TLS, EWS and TAF15 have a similar structure, characterised by an N-terminal QGSY-rich region, a highly conserved RNA recognition motif (RRM), multiple RGG repeats, which are extensively demethylated at arginine residues and a C-terminal zinc finger motif.
Function
The N-terminal end of FUS appears to be involved in transcriptional activation, while the C-terminal end is involved in protein and RNA binding. In addition recognition sites for the transcription factors AP2, GCF, Sp1 have been identified in FUS.
Consistently, in vitro studies have shown that FUS/TL |
https://en.wikipedia.org/wiki/Glypican%203 | Glypican-3 is a protein that, in humans, is encoded by the GPC3 gene. The GPC3 gene is located on human X chromosome (Xq26) where the most common gene (Isoform 2, GenBank Accession No.: NP_004475) encodes a 70-kDa core protein with 580 amino acids. Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).
Structure and function
The protein core of GPC3 consists of two subunits, where the N-terminal subunit has a size of ~40 kDa and the C-terminal subunit is ~30 kDa. Six glypicans (GPC1-6) have been identified in mammals. Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. GPC3 has been found to regulate Wnt/β-catenin and Yap signaling pathways. GPC3 interacts with both Wnt and frizzled (FZD) to form a complex and triggers downstream signaling. The core protein of GPC3 may serve as a co-receptor or a receiver for Wnt. A cysteine-rich domain at the N-lobe of GPC3 has been identified as a hydrophobic groove that interacts with Wnt3a. Blocking the Wnt binding domain on GPC3 using the HN3 single domain antibo |
https://en.wikipedia.org/wiki/Laminin%20subunit%20alpha-2 | Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.
Function
Laminin, an extracellular matrix protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
LOVD mutation database: LAMA2
Laminins |
https://en.wikipedia.org/wiki/LMAN1 | Protein ERGIC-53 also known as ER-Golgi intermediate compartment 53 kDa protein or lectin mannose-binding 1 is a protein that in humans is encoded by the LMAN1 gene.
Function
ERGIC-53 (also named LMAN1) is a type I integral membrane protein localized in the intermediate region (ERGIC) between the endoplasmic reticulum and the Golgi, presumably recycling between the two compartments. The protein is a mannose-specific lectin and is a member of a novel family of plant lectin homologs in the secretory pathway of animal cells. Mutations in the gene are associated with a coagulation defect. Using positional cloning, the gene was identified as the disease gene leading to combined deficiency of factor V-factor VIII, a rare, autosomal recessive disorder in which both coagulation factors V and VIII are diminished. MCFD2 is the second gene that leads to combined deficiency of factor V-factor VIII. ERGIC-53 and MCFD2 form a protein complex and serve as a cargo receptor to transport FV and FVIII from the ER to the ERGIC and then the Golgi,as illustrated here.
Clinical significance
LMAN1 mutational inactivation is a frequent and early event potentially contributing to colorectal tumorigenesis.
References
Further reading |
https://en.wikipedia.org/wiki/Matrix%20metallopeptidase%2012 | Matrix metalloproteinase-12 (MMP-12) also known as macrophage metalloelastase (MME) or macrophage elastase (ME) is an enzyme that in humans is encoded by the MMP12 gene.
Function
Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins. The prodomain is cleaved by extracellular proteinases when the enzyme is activated. The active enzyme is constituted by two domains, the catalytic domain responsible for its enzymatic activity and the hemopexin-like domain that in some MMPs plays a role in substrate recognition and can contribute to increasing catalytic efficiency. It is thought that the protein encoded by this gene is cleaved at both ends to yield the active enzyme, but this processing has not been fully described. The enzyme degrades soluble and insoluble elastin. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.
Clinical significance
MMP12 may play a role in aneurysm formation and studies in mice and humans suggest a role in the development of emphysema.
References
Further reading
External links
The MEROPS online database for peptidases and their inhibitors: M10.009
PDBe-KB provides an overview of all the structure information available in the PDB for Human Macrophage |
https://en.wikipedia.org/wiki/MST1R | Macrophage-stimulating protein receptor is a protein that in humans is encoded by the MST1R gene. MST1R is also known as RON (Recepteur d'Origine Nantais) kinase, named after the French city in which it was discovered. It is related to the c-MET receptor tyrosine kinase.
Interactions
MST1R has been shown to interact with Grb2.
References
Further reading
Tyrosine kinase receptors |
https://en.wikipedia.org/wiki/CEACAM6 | Carcinoembryonic antigen-related cell adhesion molecule 6 (non-specific cross reacting antigen) (CEACAM6) also known as CD66c (Cluster of Differentiation 66c), is a member of the carcinoembryonic antigen (CEA) gene family..
See also
Cluster of differentiation
References
Further reading
External links
Clusters of differentiation |
https://en.wikipedia.org/wiki/PIK3CB | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform is an enzyme that in humans is encoded by the PIK3CB gene.
Phosphoinositide 3-kinases (PI3Ks) phosphorylate the 3-prime OH position of the inositol ring of inositol lipids. They have been implicated as participants in signaling pathways regulating cell growth by virtue of their activation in response to various mitogenic stimuli. PI3Ks are composed of a 110-kD catalytic subunit, such as PIK3CB, and an 85-kD adaptor subunit (Hu et al., 1993).[supplied by OMIM]
References
Further reading |
https://en.wikipedia.org/wiki/PSMB6 | Proteasome subunit beta type-6 also known as 20S proteasome subunit beta-1 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB6 gene.
This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-6, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Caspase-like" activity and is capable of cleaving after acidic residues of peptide. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.
Structure
Gene
The human gene contains 6 exons and is located at chromosome band 17p13.
Protein
The human protein proteasome subunit beta type-6 is 22 kDa in size and composed of 205 amino acids. The calculated theoretical pI of this protein is 4.91.
The 20S proteasome subunit beta-1 (systematic nomenclature) is originally expressed as a precursor with 239 amino acids. The fragment of 34 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At th |
https://en.wikipedia.org/wiki/PSMD9 | 26S proteasome non-ATPase regulatory subunit 9 is an enzyme that in humans is encoded by the PSMD9 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator.
Clinical significance
The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in |
https://en.wikipedia.org/wiki/Troponin%20C%20type%201 | Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle (cardiac, fast-twitch skeletal, or slow-twitch skeletal) and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.
Structure
Cardiac troponin C (cTnC) is a 161-amino acid protein organized into two domains: the regulatory N-terminal domain (cNTnC, residues 1-86), the structural C-terminal domain (cCTnC, residues 93-161), and a flexible linker connecting the two domains (residues 87-92). Each domain contains two EF-hands, Ca2+-binding helix-loop-helix motifs exemplified by proteins like parvalbumin and calmodulin. In cCTnC the two EF-hand motifs constitute two high affinity Ca2+-binding sites. that are occupied at all physiologically relevant calcium concentrations. In contrast, only the second EF-hand in cNTnC binds Ca2+ with low affinity, while the first EF-hand Ca2+-binding site is defunct.
In a typical EF-hand protein like calmodulin, Ca2+ binding induces a closed-to-open conformational transition, exposing a large hydrophobic patch in the open state. Likewise, the cardiac troponin regulatory domain, cNTnC, is in a closed conformation in the apo state (no calcium bound). Upon Ca2+ binding, cNTnC enters into a rapid equilibrium between closed and open forms, however, the closed form still predominates. The structural domain, cCTnC, exi |
https://en.wikipedia.org/wiki/IKBKE | Inhibitor of nuclear factor kappa-B kinase subunit epsilon also known as I-kappa-B kinase epsilon or IKK-epsilon is an enzyme that in humans is encoded by the IKBKE gene.
Interactions
IKBKE has been shown to interact with TANK.
Function
It is a Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD (TANK-binding kinase 1-binding protein 1) can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultim |
https://en.wikipedia.org/wiki/B-cell%20linker | B-cell linker (BLNK) protein is expressed in B cells and macrophages and plays a large role in B cell receptor signaling. Like all adaptor proteins, BLNK has no known intrinsic enzymatic activity. Its function is to temporally and spatially coordinate and regulate downstream signaling effectors in B cell receptor (BCR) signaling, which is important in B cell development. Binding of these downstream effectors is dependent on BLNK phosphorylation. BLNK is encoded by the BLNK gene and is also known as SLP-65, BASH, and BCA.
Structure and localization
BLNK consists of a N-terminal leucine zipper motif followed by an acidic region, a proline-rich region, and a C-terminal SH2 domain. The leucine zipper motif allows BLNK to localize to the plasma membrane, presumably by coiled-coil interactions with a membrane protein. This leucine zipper motif distinguishes BLNK from lymphoctye cytosolic protein 2, also known as LCP-2 or SLP-76, which plays a similar role in T cell receptor signaling. Although LCP-2 has an N-terminal heptad-like organization of leucine and isoleucine residues like BLNK, it has not been experimentally shown to have the leucine zipper motif. Recruitment of BLNK to the plasma membrane is also achieved by binding of the SH2 domain of BLNK to a non-ITAM phospho-tyrosine on the cytoplasmic domain of CD79A, which is a part of Igα and the B cell receptor complex.
Function
BLNK's function and importance in B cell development were first illustrated in BLNK deficient DT4 |
https://en.wikipedia.org/wiki/Calsenilin | Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.
Function
This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the neuronal calcium sensor family of proteins. Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. In addition, the protein has been shown to transcriptionally repress A20 (TNFAIP3) expression and thus modulate the anti-inflammatory signaling. Alternatively spliced transcript variants encoding different isoforms have been described.
Interactions
Calsenilin has been shown to interact with PSEN1 and PSEN2.
See also
Voltage-gated potassium channel
References
Further reading
External links
NCS proteins
EF-hand-containing proteins |
https://en.wikipedia.org/wiki/APBA1 | Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.
Function
The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adaptor protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilises APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion.
Interactions
APBA1 has been shown to interact with KCNJ12, CCS, CASK and Amyloid precursor protein.
References
Further reading
External links |
https://en.wikipedia.org/wiki/Bcl-2-interacting%20killer | Bcl-2-interacting killer is a protein that in humans is encoded by the BIK gene.
Function
The protein encoded by this gene is known to interact with cellular and viral survival-promoting proteins, such as BCL2 and the Epstein–Barr virus in order to enhance programmed cell death. Because its activity is suppressed in the presence of survival-promoting proteins, this protein is suggested as a likely target for antiapoptotic proteins. This protein shares a critical BH3 domain with other death-promoting proteins, BAX and BAK.
Interactions
Bcl-2-interacting killer has been shown to interact with BCL2-like 1 and Bcl-2.
References
External links
Further reading |
https://en.wikipedia.org/wiki/Collagen%2C%20type%20IV%2C%20alpha%206 | Collagen alpha-6(IV) chain is a protein that in humans is encoded by the COL4A6 gene.
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Two splice variants have been identified for this gene.
References
Further reading
Collagens |
https://en.wikipedia.org/wiki/MAP3K8 | Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene.
Function
The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases. This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer. However, it functions in other organs as a oncogene, promoting cancer.
Interactions
MAP3K8 has been shown to interact with AKT1, CHUK, NFKB2, NFKB1, C22orf25 and TNIP2.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/EPH%20receptor%20A4 | EPH receptor A4 (ephrin type-A receptor 4) is a protein that in humans is encoded by the EPHA4 gene.
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.
In 2012, a publication in Nature Medicine revealed a connection between EPHA4 and the neurodegenerative disease Amyotrophic lateral sclerosis (ALS), where a defective gene allows ALS patients to live considerably longer than patients with an intact gene. This opens up for development of treatment for this currently untreatable disease.
References
Further reading
Tyrosine kinase receptors |
https://en.wikipedia.org/wiki/FLNC%20%28gene%29 | Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.
Structure
Filamin-C is a 290.8 kDa protein composed of 2725 amino acids. Filamin-C, like the ubiquitously-expressed isoform Filamin-A, have an N-terminal filamentous actin-binding domain, followed by a lengthy C-terminal self-association domain containing a series of immunoglobulin-like domains, and a membrane glycoprotein-binding domain. Filamin-C interacts with γ-sarcoglycan and δ-sarcoglycan at the sarcolemma; myotilin and FATZ/calsarcin/myozenin at Z-lines, as well as LL5β. Filamin-C has also been shown to interact with INPPL1, KCND2, and MAP2K4.
Function
The family of Filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. However, the precise function of the Filamin-C isoform is still under investigation. As Filamin-C is localized mainly to striated muscle, its functions are likely specific to the specialized sarcomeric cytoskeleton present in muscle. As Filamin-C is found at both subsarcolemmal regions and at Z-lines, one plausible function of Filamin-C would be to act as a mode of communication between the membrane and the sarcomere. In skeletal muscle, Filamin-C is found at sites of core form |
https://en.wikipedia.org/wiki/GP1BB | Glycoprotein Ib (platelet), beta polypeptide (GP1BB) also known as CD42c (Cluster of Differentiation 42c), is a protein that in humans is encoded by the GP1BB gene.
Function
Platelet glycoprotein Ib (GPIb) is a heterodimeric transmembrane protein consisting of a disulfide-linked 140 kD alpha chain and 22 kD beta chain. It is part of the Glycoprotein Ib-IX-V Receptor Complex (GPIb-V-IX) system that constitutes the receptor for von Willebrand factor (VWF), and mediates platelet adhesion in the arterial circulation. GPIb alpha chain provides the VWF binding site, and GPIb beta contributes to surface expression of the receptor and participates in transmembrane signaling through phosphorylation of its intracellular domain. Mutations in the GPIb beta subunit have been associated with Bernard–Soulier syndrome, velocardiofacial syndrome and giant platelet disorder. The 206 amino acid precursor of GPIb beta is synthesized from a 1.0 kb mRNA expressed in plateletes and megakaryocytes. A 411 amino acid protein arising from a longer, unspliced transcript in endothelial cells has been described; however, the authenticity of this product has been questioned. Yet another less abundant GPIb beta mRNA species of 3.5 kb, expressed in nonhematopoietic tissues such as endothelium, brain and heart, was shown to result from inefficient usage of a non-consensus polyA signal within a separate gene (septin 5) located upstream of this gene. In the absence of polyadenylation from its own imperfect s |
https://en.wikipedia.org/wiki/Histidine-rich%20glycoprotein | Histidine-rich glycoprotein (HRG) is a glycoprotein that in humans is encoded by the HRG gene. The HRG protein is produced in the liver, and it could also be synthesized by monocytes, macrophages, and megakaryocytes. It possesses a multi-domain structure, which makes it capable of binding to numerous ligands and modulating various biological processes including immunity, vascularization and coagulation.
Structure
Gene
The HRG gene lies on location of 3q27 on the chromosome 3, spans approximately 11kb, and consist of 7 exons. Two common isoforms of the HRG gene have been found in humans. These isoforms exist due to a polymorphism occurring in exon 5.
Protein
HRG is a glycoprotein of 70-75kDa present at a relatively high concentration in the plasma of vertebrates. The primary structure of human HRG is predicted to be a 507 amino acid multidomain polypeptide consisting of two cystatin-like regions at the N-terminus, a histidine-rich region (HRR) flanked by proline-rich regions (PRR), and a C-terminal domain. HRG has an unusually high concentration of histidine and proline residues, each constituting approximately 13% of total amino acids, concentrated within the HRR and PRR. The high concentration of both histidine and proline residues has resulted in HRG also being termed 'histidine–proline-rich glycoprotein' (HPRG). Human HRG is also composed of approximately 14% carbohydrate attached to six predicted N-linked glycosylation sites.
Function
This histidine-rich glycoprote |
https://en.wikipedia.org/wiki/MTRR%20%28gene%29 | Methionine synthase reductase, also known as MSR, is an enzyme that in humans is encoded by the MTRR gene.
Function
Methionine is an essential amino acid required for protein synthesis and one-carbon metabolism. Its synthesis is catalyzed by the enzyme methionine synthase. Methionine synthase eventually becomes inactive due to the oxidation of its cobalamin cofactor. Methionine synthase reductase regenerates a functional methionine synthase via reductive methylation. It is a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases.
Methionine synthase reductase (MTRR) is primarily involved in the reductive methylation of homocysteine to methionine, utilizing methylcob(I)alamin as an intermediate methyl carrier. Methionine is an essential amino acid in mammals, necessary for protein synthesis and one carbon metabolism. In its activated form, S-adenosylmethionine acts as a methyl donor in biological transmethylation reactions and as a propylamine donor in polyamine synthesis. A major product of methionine demethylation is homocysteine. Remethylation of homocysteine occurs via a cobalamin dependent enzyme, methionine synthase (MTR). The folate cycle is linked to homocysteine metabolism via MTR. Circulating blood folate (5-methyl tetrahydrofolate, 5-MTHF) donates methyl groups to MTR to be utilized in cellular methylation. A methyl cobalt bond of the intermediary methyl carrier, methlycob(III)alamin is cleaved heterolytically producing cobalamin in it |
https://en.wikipedia.org/wiki/PTS%20%28gene%29 | 6-pyruvoyltetrahydropterin synthase, also known as PTS, is a human gene which facilitates folate biosynthesis.
See also
6-pyruvoyltetrahydropterin synthase
6-Pyruvoyltetrahydropterin synthase deficiency
References
Further reading |
https://en.wikipedia.org/wiki/40S%20ribosomal%20protein%20S19 | 40S ribosomal protein S19 is a protein that in humans is encoded by the RPS19 gene.
Function
Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.
Clinical significance
Mutations in this gene cause Diamond–Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed.
Interactions
Ribosomal protein S19 has been shown to interact with basic fibroblast growth factor. RPS19 is also secreted extracellularly and its extracellular oligomers (crosslinked by the transglutaminase Coagulation factor XIII) is also known to bind and probably inhibit Macrophage migration inhibitory factor; though S19 oligomers themselves share MCIP's function as anoth |
https://en.wikipedia.org/wiki/Retinoschisin | Retinoschisin also known as X-linked juvenile retinoschisis protein is a lectin that in humans is encoded by the RS1 gene.
It is a soluble, cell-surface protein that plays an important role in the maintenance of the retina where it is expressed and secreted by retinal bipolar cells and photoreceptors, as well as in the pineal gland. Retinoschisin (RS1) is encoded by the gene RS1 located on the X chromosome at p22.1. Young males who have an RS1 mutation are susceptible to retinoschisis, and X-linked eye disease which causes macular degeneration and can lead to a loss of vision.
Function
Retinoschisin is an extracellular protein that plays a crucial role in the cellular organization of the retina: it binds the plasma membranes of various retinal cells tightly to maintain the structure of the retina. In addition to enabling cell-to-cell adhesion, it has been shown that retinoschisin interacts with the sodium/potassium-ATPase (Na/K-ATPase) which resides in the plasma membrane. RS1 also plays a role in the regulation on intracellular MAP kinase signalling.
Structure
The retinoschisin monomer is 224 amino acids long, including a 23-amino acid signal peptide essential for secretion (this is cleaved off before the protein becomes functional), and a highly conserved sequence motif called the discoidin domain which consists of 157 amino acids, important for the protein's function in cell to cell adhesion. However, its oligomeric structure is a pairing of back-to-back octamers, for |
https://en.wikipedia.org/wiki/TYRP1 | Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene.
Function
Tyrp1 is a melanocyte-specific gene product involved in melanin synthesis within melanosomes. Most Tyrp1 possess 5,6-dihydroxyindole-2-carboxylic acid (melanogenic intermediate) oxidase activity. The catalytic function of Tyrp1 in human melanocytes is less clear. Tyrp1 is involved in stabilizing of tyrosinase protein and modulating its catalytic activity. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and melanocyte cell death. Melanocytes are derived from the neural crest and migrate into the overlying epidermal ectoderm of a developing organism which forms skin and hair. Therefore, Tyrp1 influences the expression of melanin notably in the skin and hair of an organism.
The Tyrp1 gene also has a non-coding function which indirectly promotes melanoma tumor cell proliferation, especially when highly expressed in a cell. Tyrp1 mRNA interacts with miR-16 and affects its ability to repress genes involved in melanoma cell production.
Clinical significance
Mutations in the mouse Tyrp1 gene are associated with brown pelage and in the human TYRP1 gene with oculocutaneous albinism type 3 (OCA3). An allele of TYRP1 common in Solomon Islanders results in blond hair. Although the phenotype is similar to Northern European blond hair, this allele is not found in Europeans. More recent study, Ju et al |
https://en.wikipedia.org/wiki/Zyxin | Zyxin is a protein that in humans is encoded by the ZYX gene.
Function
Focal adhesions are actin-rich structures that enable cells to adhere to the extracellular matrix and at which protein complexes involved in signal transduction assemble. Zyxin is a zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half. The proline-rich domain may interact with SH3 domains of proteins involved in signal transduction pathways while the LIM domains are likely involved in protein-protein binding. Zyxin may function as a messenger in the signal transduction pathway that mediates adhesion-stimulated changes in gene expression and may modulate the cytoskeletal organization of actin bundles. Alternative splicing results in multiple transcript variants that encode the same isoform.
Interactions
Zyxin has been shown to interact with:
Actinin, alpha 1
ENAH,
LASP1,
LATS1, and
Vasodilator-stimulated phosphoprotein.
References
Further reading
External links
Zyxin Info with links in the Cell Migration Gateway
Cytoskeleton |
https://en.wikipedia.org/wiki/Tubulin%20alpha-1A%20chain | Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.
Background
Tubulin alpha-1A chain is an alpha-tubulin that participates in the formation of microtubules - structural proteins that participate in cytoskeletal structure. Specifically, microtubules are composed of a heterodimer of alpha and beta-tubulin molecules. Cowan et al. demonstrated that bα1 is a primary α-tubulin of the human fetal brain, and that it is expressed solely in that structure, by way of Northern blot. Miller et al. further elaborated on the role of α-tubulins and the process of neuronal development and maturation, comparing the expressions of rat α-tubulins Tα1 and T26. These two rat α-tubulins are homologs of bα1 and kα1 showing that a rat homolog of human TUBA1A (Tα1) had elevated expression during the extension of neuronal processes. Culturing of pheochromocytoma cells with Nerve Growth Factor (NGF) induced differentiation and the development of neuronal processes. Northern blot assay showed markedly elevated levels of Tα1 mRNA expression; T26 mRNA expression increased minimally with exposure to NGF. These data suggest that TUBA1A models the brain by participating in the directing of neuronal migration through the ability of microtubules to readily form and break polymers to extend and retract processes to induce nucleokinesis. Poirier et al. used RNA in situ hybridization to show TUBA1A expression in mice embryo; embryo sections from embryonic day 16.5 “showed a strong l |
https://en.wikipedia.org/wiki/Electrogenic%20sodium%20bicarbonate%20cotransporter%201 | Electrogenic sodium bicarbonate cotransporter 1, sodium bicarbonate cotransporter is a membrane transport protein that in humans is encoded by the SLC4A4 gene.
Function
Sodium bicarbonate cotransporters (NBCs) mediate the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. This is an electrogenic process with an apparent stoichiometry of 3 bicarbonate ions per sodium ion. Sodium bicarbonate co-transport is involved in bicarbonate secretion/absorption and intracellular pH regulation. Romero and Boron (1999) reviewed NBCs. Soleimani and Burnham (2000) reviewed NBCs and their regulation in physiologic and pathophysiologic states.[supplied by OMIM]
Clinical significance
In the brain, the sodium bicarbonate transporter is predominantly expressed by astrocytes. They may participate in regulation of brain extracellular space pH. Some mutations in the gene have been associated with familial hemiplegic migraine. Other mutations disrupt kidney bicarbonate transport and cause proximal renal tubular acidosis.
Splice variants
NBCe1-A aka kNBC1 (mainly expressed in the kidney)
NBCe1-B aka pNBC1 (expressed in the pancreas and elsewhere)
NBCe1-C (expressed in the brain)
Distribution
The renal SLC4A4 gene product NBCe1-A is specifically expressed in the basolateral membranes of proximal tubule epithelia.
See also
Solute carrier family
References
Further reading
Solute carrier family |
https://en.wikipedia.org/wiki/Barrier%20to%20autointegration%20factor%201 | Barrier-to-autointegration factor is a protein that in humans is encoded by the BANF1 gene. It is a member of the barrier-to-autointegration factor family of proteins.
Function
The protein encoded by this gene was identified by its ability to protect retroviruses from intramolecular integration and therefore promote intermolecular integration into the host cell genome. The endogenous function of the protein is unknown. The protein forms a homodimer which localizes to the nucleus and is specifically associated with chromosomes during mitosis. This protein binds to DNA in a non-specific manner and studies in rodents suggest that it also binds to lamina-associated polypeptide 2, a component of the nuclear lamina. It also associates with the LEM Domain containing proteins LAP2, Emerin, and MAN1. The protein's DNA binding ability is modulated by ATP concentration.
Interactions
Barrier to autointegration factor 1 has been shown to interact with Thymopoietin.
Clinical relevance
Mutations in this gene have been shown to cause hereditary progeroid syndrome.
See also
Retroviral integration
References
Further reading
External links |
https://en.wikipedia.org/wiki/TNK2 | Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene.
TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.
Interactions
ACK1 or TNK2 has been shown to interact with AKT, Androgen receptor or AR, a tumor suppressor WWOX, FYN and Grb2. ACK1 interaction with its substrates resulted in their phosphorylation at specific tyrosine residues. ACK1 has been shown to directly phosphorylate AKT at tyrosine 176, AR at Tyrosine 267 and 363, and WWOX at tyrosine 287 residues, respectively. ACK1-AR signaling has also been reported to regulate ATM levels,
Clinical relevance
ACK1 is a survival kinase and shown to be associated with tumor cell survival, proliferation, hormone-resistance and radiation resistance. The activation of ACK1 |
https://en.wikipedia.org/wiki/Cyclin%20O | Cyclin-O is a protein that in humans is encoded by the CCNO gene.
Interactions
Cyclin O has been shown to interact with RPA2 and PCNA.
References
Further reading
External links |
https://en.wikipedia.org/wiki/ATP2C1 | Calcium-transporting ATPase type 2C member 1 is an enzyme that in humans is encoded by the ATP2C1 gene.
This gene encodes one of the SPCA proteins, a Ca2+ ion-transporting P-type ATPase. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified.
References
External links
Further reading |
https://en.wikipedia.org/wiki/Reticulon%204%20receptor | Reticulon 4 receptor (RTN4R) also known as Nogo-66 Receptor (NgR) or Nogo receptor 1 is a protein which in humans is encoded by the RTN4R gene. This gene encodes the receptor for reticulon 4, oligodendrocytemyelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system.
Function
The Nogo-66 Receptor (NgR) is a high affinity binding receptor for a region of Nogo, a myelin associated protein that inhibits axon outgrowth. NgR was identified by Strittmatter and colleagues using an expression cloning strategy.
NgR is implicated in neuronal plasticity and regeneration. Its relative importance in mediating myelin inhibition in vitro and in vivo is currently under intense investigation, since this protein might be a good drug target for treatment of various neurological conditions such as spinal cord injury and stroke.
Nogo pathway: rho kinase
While the entire pathway is not fully understood, the relationship between NgR and neuronal outgrowth has been fleshed out. NgR is a membrane protein that, when bound to neurite outgrowth inhibitor (Nogo), inhibits cell growth through the activation of rho kinase (ROCK).
NgR activation of p75
It was known that NgR, Nogo, and another membrane receptor called p75 were involved in inhibiting neurite outgrowth. Through a variety of experimental procedures Wang et al. were able to identify the bi |
https://en.wikipedia.org/wiki/ATP2A1 | Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) also known as Calcium pump 1, is an enzyme that in humans is encoded by the ATP2A1 gene.
Function
This gene encodes one of the SERCA Ca2+-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction.
Clinical significance
Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms.
Alternative splicing of ATP2A1 is also implicated in myotonic dystrophy type 1.
ATP2A1 SERCA pumps were very strongly down regulated in amyotrophic lateral sclerosis.
Interactions
ATP2A1 has been shown to interact with:
SLN, and
PLN.
References
External links
Further reading |
https://en.wikipedia.org/wiki/FOXL2 | Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.
Function
FOXL2 (OMIM 605597) is a transcription factor belonging to the forkhead box (FOX) superfamily, characterized by the forkhead box/winged-helix DNA-binding domain.
FOXL2 plays an important role in ovarian development and function. In postnatal ovaries FOXL2 regulates granulosa cell differentiation and supports the growth of the pre-ovulatory follicles during adult life.
In addition, the FOXL2 protein will prevent the formation of testes by suppressing expression of SOX9. In mice, FOXL2 is also expressed in pituitary cells where it is required for FSH expression.
Regulation
FOXL2 has several post-translational modifications that modulate its stability, subcellular localization and pro-apoptotic activity. By a yeast-two-hybrid screening, 10 novel protein partners of FOXL2 were discovered. The interactions were confirmed by co-immunoprecipitation experiments between FOXL2 and CXXC4 (IDAX), CXXC5 (RINF/WID), CREM, GMEB1 (P96PIF), NR2C1 (TR2), SP100, RPLP1, BAF (BANF1), XRCC6 (KU70) and SIRT1.
Clinical significance
Sex determination
FOXL2 is involved in sex determination. FOXL2 knockout in mature mouse ovaries appears to cause the ovary's somatic cells to transdifferentiate to the equivalent cell types ordinarily found in the testes. Polled Intersex Syndrome in goats is caused by a biallelic loss-of-function in FOXL2 transcription and leads to in utero female-to-male sex-reversal.
Ey |
https://en.wikipedia.org/wiki/CHRNA3 | Neuronal acetylcholine receptor subunit alpha-3, also known as nAChRα3, is a protein that in humans is encoded by the CHRNA3 gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR). Research with mecamylamine in animals has implicated alpha-3-containing nAChRs in the abusive and addictive properties of ethanol.
Interactive pathway map
See also
Nicotinic acetylcholine receptor
References
Further reading
External links
Nicotinic acetylcholine receptors |
https://en.wikipedia.org/wiki/CYP24A1 | Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the CYP24A1 gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D3). It has also been identified as vitamin D3 24-hydroxylase.()
Function
CYP24A1 is an enzyme expressed in the mitochondrion of humans and other species. It catalyzes hydroxylation reactions which lead to the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D. Hydroxylation of the side chain produces calcitroic acid and other metabolites which are excreted in bile.
CYP24A1 was identified in the early 1970s and was first thought to be involved in vitamin D metabolism as the renal 25-hydroxyvitamin D3-24-hydroxylase, modifying calcifediol (25-hydroxyvitamin D) to produce 24,25-dihydroxycholecalciferol (24,25-dihydroxyvitamin D). Subsequent studies using recombinant CYP24A1 showed that it could also catalyze multiple other hydroxylation reactions at the side chain carbons known as C-24 and C-23 in both 25-OH-D3 and the active hormonal form, 1,25-(OH)2D3. It is now considered responsible for the entire five-step, 24-oxidation pathway from 1,25-(OH)2D3 producing calcitroic acid.
CYP24A1 also is able to catalyse another pathway which starts with 23-hydroxylation of 1,25-(OH)2D3 and culminates in 1,25-(OH)2D3-26,23-lactone.
The side chains of the ergocalciferol |
https://en.wikipedia.org/wiki/Endothelin%203 | Endothelin-3 is a protein that in humans is encoded by the EDN3 gene.
The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety of biological functions. The active form of this protein is a 21 amino acid peptide processed from the precursor protein. The active peptide is a ligand for endothelin receptor type B (EDNRB). The interaction of this endothelin with EDNRB is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. Mutations in this gene and EDNRB have been associated with Hirschsprung disease (HSCR) and Waardenburg syndrome (WS), which are congenital disorders involving neural crest-derived cells. Four alternatively spliced transcript variants encoding three distinct isoforms have been observed.
References
Further reading
Endothelin receptor agonists |
https://en.wikipedia.org/wiki/EPH%20receptor%20B1 | Ephrin type-B receptor 1 is a protein that in humans is encoded by the EPHB1 gene.
Function
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members.
Interactions
EPH receptor B1 has been shown to interact with:
ACP1
GRB7 and
NCK1
Ephrin-B2
References
Further reading |
https://en.wikipedia.org/wiki/Glycoprotein%20IX | Glycoprotein IX (platelet) (GP9) also known as CD42a (Cluster of Differentiation 42a), is a human gene.
Platelet glycoprotein IX (GP9) is a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib (GP Ib), a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor (VWF; MIM 193400) (known as the Glycoprotein Ib-IX-V Receptor Complex). The main portion of the receptor is a heterodimer composed of 2 polypeptide chains, an alpha chain (GP1BA; MIM 606672) and a beta chain (GP1BB; MIM 138720), that are linked by disulfide bonds. The complete receptor complex includes noncovalent association of the alpha and beta subunits with GP9 and platelet glycoprotein V (GP5; MIM 173511).[supplied by OMIM]
See also
Cluster of differentiation
References
Further reading
External links
Clusters of differentiation |
https://en.wikipedia.org/wiki/Integrin%20beta%207 | Integrin beta-7 is an integrin protein that in humans is encoded by the ITGB7 gene. It can pair with ITGA4 (CD49d) to form the heterodimeric integrin receptor αβ, or with ITGAE (CD103) to form αβ.
Structure
Like all integrin subunits, β is a highly flexible, membrane-bound, extracellular protein that must pair with an α subunit for stability. The molecule's flexibility allows it to dynamically regulate its affinity for ligand through conformational changes. Beginning with the apical end of the protein, farthest from the cell membrane, the β is composed of a head and upper legs, collectively known as the headpiece, lower legs, a transmembrane domain and a cytoplasmic tail. The top of the head is the I-like domain, sometimes called the βI domain, which, in combination with the α subunit, binds ligand. Just below this is the hybrid domain, a portion of which is N-terminal to the I-like domain. Below the hybrid domain is the PSI domain, which completes the headpiece. The lower legs consist of EGF domains 1-4 and the β tail domain. Finally there is a transmembrane domain, and the C-terminal cytoplasmic tail.
Interactions
ITGB7 has been shown to interact with EED.
References
Further reading
External links
ITGB7 Info with links in the Cell Migration Gateway
Integrins |
https://en.wikipedia.org/wiki/KCND2 | Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.
Description
Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels.
Interactions
KCND2 has been shown to interact with FLNC.
See also
Voltage-gated potassium channel
References
Further reading
External links |
https://en.wikipedia.org/wiki/Megakaryocyte-associated%20tyrosine%20kinase | Megakaryocyte-associated tyrosine-protein kinase is an enzyme that in humans is encoded by the MATK gene.
The protein encoded by this gene has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer. Three alternatively spliced transcript variants that encode different isoforms have been described for this gene.
Interactions
Megakaryocyte-associated tyrosine kinase has been shown to interact with CD117 and TrkA.
References
Further reading
Human proteins
Tyrosine kinases |
https://en.wikipedia.org/wiki/Metallothionein%201A | Metallothionein-1A is a protein that in humans is encoded by the MT1A gene.
References
Further reading
Human proteins |
https://en.wikipedia.org/wiki/PPP1R12A | Protein phosphatase 1 regulatory subunit 12A is an enzyme that in humans is encoded by the PPP1R12A gene.
Myosin phosphatase target subunit 1, which is also called the myosin-binding subunit of myosin phosphatase, is one of the subunits of myosin phosphatase. Myosin phosphatase regulates the interaction of actin and myosin downstream of the guanosine triphosphatase Rho. The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP. RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase.
Interactions
PPP1R12A has been shown to interact with Interleukin 16.
References
Further reading
External links
PPP1R12A Info with links in the Cell Migration Gateway |
https://en.wikipedia.org/wiki/Peptidylglycine%20alpha-amidating%20monooxygenase | Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that catalyzes the conversion of glycine amides to amides and glyoxylate.
The enzyme is involved in the biosynthesis of many signaling peptides and some fatty acid amides.
In humans, the enzyme is encoded by the PAM gene. This transformation is achieved by conversion of a prohormone to the corresponding amide (C(O)NH2). This enzyme is the only known pathway for generating peptide amides, which renders the peptide more hydrophilic.
Function
This gene encodes a multifunctional protein. It has two enzymatically active domains with catalytic activities - peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). These catalytic domains work sequentially to catalyze neuroendocrine peptides to active alpha-amidated products. The reaction pathway catalyzed by PAM is accessed via quantum tunneling and substrate preorganization. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene, but some of their full-length sequences are not yet known.
The PHM subunit effects hydroxylation of an O-terminal glycine residue:
peptide-C(O)NHCH2CO2− + O2 + 2 [H] → peptide-C(O)NHCH(OH)CO2− + H2O
Involving hydroxylation of a hydrocarbon by O2, this process relies on a copper cofactor. Dopamine beta-hydroxylase, also a copper-containing enzyme, effects a similar transformation.
The PAL subunit then completes t |
https://en.wikipedia.org/wiki/Programmed%20cell%20death%20protein%201 | Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.
PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).
PD-1 inhibitors, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer.
The PD-1 protein in humans is encoded by the PDCD1 gene. PD-1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells and pro-B cells. PD-1 binds two ligands, PD-L1 and PD-L2.
Discovery
In a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University in 1992 discovered and named PD-1. In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses.
Structure
PD-1 is a type I membrane protein of 288 amino acid |
https://en.wikipedia.org/wiki/RNASE1 | Ribonuclease pancreatic is an enzyme that in humans is encoded by the RNASE1 gene.
Function
This gene encodes a member of the pancreatic-type of secretory ribonucleases, a subset of the ribonuclease A super-family. The encoded endonuclease cleaves internal phosphodiester RNA bonds on the 3'-side of pyrimidine bases. It prefers poly(C) as a substrate and hydrolyses 2',3'-cyclic nucleotides, with a pH optimum near 8.0. The encoded protein is monomeric and more commonly acts to degrade ss-RNA over ds-RNA. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified.
References
Further reading
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human Ribonuclease pancreatic |
https://en.wikipedia.org/wiki/SPTBN1 | Spectrin beta chain, brain 1 is a protein that in humans is encoded by the SPTBN1 gene.
Function
Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats that are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene.
Interactions
SPTBN1 has been shown to interact with Merlin.
Model organisms
Model organisms have been used in the study of spectrin function. A conditional knockout mouse line, called Spnb2tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and four significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation and those that were present displayed oedema. None survived until weaning. The remaining tests were carried out on heterozygous mutant |
https://en.wikipedia.org/wiki/EIF2B5 | Translation initiation factor eIF-2B subunit epsilon is a protein that in humans is encoded by the EIF2B5 gene.
Interactions
EIF2B5 has been shown to interact with EIF2B2 and EIF2B1.
References
Further reading |
https://en.wikipedia.org/wiki/WASF1 | Wiskott–Aldrich syndrome protein family member 1, also known as WASP-family verprolin homologous protein 1 (WAVE1), is a protein that in humans is encoded by the WASF1 gene.
Function
The protein encoded by this gene, a member of the Wiskott–Aldrich syndrome protein (WASP) family, plays a critical role downstream of Rac, a Rho-family small GTPase, through its involvement in the WAVE regulatory complex in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro.
Clinical significance
Wiskott–Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton.
Interactions
WASF1 has been shown to interact with BAIAP2 and Profilin 1.
References
Further reading |
https://en.wikipedia.org/wiki/BCAP31 | B-cell receptor-associated protein 31 is a protein that in humans is encoded by the BCAP31 gene.
Interactions
BCAP31 has been shown to interact with:
APP,
BCL2L1,
BCL2,
CASP8, and
VAMP3.
References
Further reading
External links |
https://en.wikipedia.org/wiki/AKAP13 | A-kinase anchor protein 13 is a protein that in humans, is encoded by the AKAP13 gene. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.
Function
A-kinase anchor protein 13/Rho guanine nucleotide exchange factor 13 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as AKAP13, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. In particular, active Rho is a major regulator of the cell actin cytoskeleton.
AKAP13 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF), and ARHGEF12 (also known as LARG). GPCR-regulated AKAP13 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. Unlike the other three members, AKAP13 does not function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins.
The A-kinase anchor |
https://en.wikipedia.org/wiki/GGA2 | ADP-ribosylation factor-binding protein GGA2 is a protein that in humans is encoded by the GGA2 gene.
Function
This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly.
Interactions
GGA2 has been shown to interact with RABEP1, Sortilin 1, BACE2 and CLINT1.
References
Further reading |
https://en.wikipedia.org/wiki/Exosome%20component%202 | Exosome component 2, also known as EXOSC2, is a protein which in humans is encoded by the EXOSC2 gene.
Function
Mammalian mRNAs contain AU-rich elements (AREs) within their three prime untranslated regions. In yeast, 3-prime-to-5-prime mRNA degradation is mediated by the exosome, a multisubunit particle. EXOSC2 (which is homologous to the yeast Rrp4 protein) is a component of the human exosome.
Interactions
Exosome component 2 has been shown to interact with:
Exosome component 4, and
Exosome component 7.
References
Further reading |
https://en.wikipedia.org/wiki/AGXT | Serine—pyruvate aminotransferase is an enzyme that in humans is encoded by the AGXT gene.
This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in this gene, some of which alter subcellular targeting, have been associated with type I primary hyperoxaluria.
See also
Peroxisomal disorder
References
External links
GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1
Further reading |
https://en.wikipedia.org/wiki/AZGP1 | Zinc-alpha-2-glycoprotein is a protein that in humans is encoded by the AZGP1 gene.
This gene expresses a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice, is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. In 2009, it was found that smoking increases expression of this gene, which is why smoking cessation leads to weight gain. Zinc-alpha-2-glycoprotein levels also rise with onset of diabetes 2, which accounts for weight loss thereafter.
References
External links
Further reading |
https://en.wikipedia.org/wiki/KLF5 | Krueppel-like factor 5 is a protein that in humans is encoded by the KLF5 gene.
Function
This gene encodes a member of the Kruppel-like factor subfamily of zinc finger proteins. Since the protein localizes to the nucleus and binds the epidermal growth factor response element, it is thought to be a transcription factor.
Interactions
KLF5 has been shown to interact with Protein SET.
See also
Kruppel-like factors
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Carboxylesterase%201 | Liver carboxylesterase 1 also known as carboxylesterase 1 (CES1, hCE-1 or CES1A1) is an enzyme that in humans is encoded by the CES1 gene. The protein is also historically known as serine esterase 1 (SES1), monocyte esterase and cholesterol ester hydrolase (CEH). Three transcript variants encoding three different isoforms have been found for this gene. The various protein products from isoform a, b and c range in size from 568, 567 and 566 amino acids long, respectively.
CES1 is present in most tissues with higher levels in the liver and low levels in the gastrointestinal tract.
Function
Carboxylesterase 1 is a serine esterase and member of a large multigene carboxylesterase family. It is also part of the alpha/beta fold hydrolase family. These enzymes are responsible for the hydrolysis of ester- and amide-bond-containing xenobiotics and drugs such as cocaine and heroin. They also hydrolyze long-chain fatty acid esters and thioesters. As part of phase II metabolism, the resulting carboxylates are then often conjugated by other enzymes to increase solubility and eventually excreted.
This enzyme is known to hydrolyze aromatic and aliphatic esters and can manage cellular cholesterol esterification levels. It may also play a role in detoxification in the lung and/or protection of the central nervous system from ester or amide compounds.
The protein contains an amino acid sequence at its N-terminus that sends it into the endoplasmic reticulum where a C-terminal sequence ca |
https://en.wikipedia.org/wiki/CHRNE | Acetylcholine receptor subunit epsilon is a protein that in humans is encoded by the CHRNE gene.
Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome.
Role in health and disease
Congenital myasthenic syndrome (CMS) is associated with genetic defects that affect proteins of the neuromuscular junction. Postsynaptic defects are the most frequent cause of CMS and often result in abnormalities in the acetylcholine receptor (AChR). The majority of mutations causing CMS are found in the AChR subunits genes.
Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult AChR subunits. Mutations of the AChR often result in endplate deficiency. The most common AChR gene mutation that underlies CMS is the mutation of the CHRNE gene. The CHRNE gene codes for the epsilon subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is associated with changing the kinetic properties of the AChR. One type of mutation of the epsilon subunit of the AChR introduces an |
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