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https://en.wikipedia.org/wiki/Forkhead%20box%20C1 | Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the FOXC1 gene.
Function
This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding fork head domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development.
Heart development and somitogenesis
FOXC1 and its close relative, FOXC2 are both critical components in the development of the heart and blood vessels, as well as the segmentation of the paraxial mesoderm and the formation of somites. Expression of the Fox proteins range from low levels in the posterior pre-somitic mesoderm (PSM) to the highest levels in the anterior PSM. Homozygous mutant embryos for both Fox proteins failed to form somites 1–8, which indicates the importance of these proteins early on in somite development.
In cardiac morphogenesis, FOXC1 and FOXC2 are required for the proper development of the cardiac outflow tract. The outflow tract forms from a cell population known as the secondary heart field. The Fox proteins are transcribed in the secondary heart field where they regulate the expression of key signaling molecules such as Fgf8, Fgf10, Tbx1, Isl1, and Bmp4.
Clinical significance
Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld–Rieger syndrome t |
https://en.wikipedia.org/wiki/HSPA9 | Mitochondrial 70kDa heat shock protein (mtHsp70), also known as mortalin, is a protein that in humans is encoded by the HSPA9 gene.
Function
The product encoded by this gene belongs to the heat shock protein 70 family which contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate proteins. This gene encodes a heat-shock cognate protein. This protein plays a role in the control of cell proliferation. It may also act as a chaperone.
Interactions
HSPA9 has been shown to interact with FGF1 and P53.
Clinical relevance and genetic deficiency
In 2015, a group around Andrea Superti-Furga showed that biallelic variants in the HSPA9 gene may result in a combination of congenital malformations called the EVEN-PLUS syndrome. These genetic variants have been shown to interfere with normal HSPA9 function
References
Further reading
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human Stress-70 protein, mitochondrial
Heat shock proteins
Molecular chaperones
Mitochondrial proteins |
https://en.wikipedia.org/wiki/Ribosomal%20protein%20SA | 40S ribosomal protein SA is a ribosomal protein that in humans is encoded by the RPSA gene. It also acts as a cell surface receptor, in particular for laminin, and is involved in several pathogenic processes.
Function
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. The RPSA gene encodes a multifunctional protein, which is both a ribosomal protein and a high-affinity, non-integrin laminin receptor. This protein has been variously called Ribosomal protein SA; RPSA; LamR; LamR1; 37 kDa Laminin Receptor Precursor; 37LRP; 67 kDa Laminin Receptor; 67LR; 37/67 kDa Laminin Receptor; LRP/LR; LBP/p40; and p40 ribosome-associated protein. Ribosomal protein SA and RPSA are the approved name and symbol. The amino acid sequence of RPSA is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of RPSA transcript is higher in colon carcinoma tissue and lung cancer cell lines than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and the |
https://en.wikipedia.org/wiki/Nuclear%20mitotic%20apparatus%20protein%201 | Nuclear mitotic apparatus protein 1 is a protein that in humans is encoded by the NUMA1 gene.
Interactions
Nuclear mitotic apparatus protein 1 has been shown to interact with PIM1, Band 4.1, GPSM2 and EPB41L1.
References
Further reading
External links |
https://en.wikipedia.org/wiki/Elafin | Elafin, also known as peptidase inhibitor 3 or skin-derived antileukoprotease (SKALP), is a protein that in humans is encoded by the PI3 gene.
Function
This gene encodes an elastase-specific protease inhibitor, which contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster.
Clinical significance
Elafin has been found to have utility in serving as a biomarker for graft versus host disease of the skin.
Elafin plays some role in gut inflammation.
References
Further reading
External links |
https://en.wikipedia.org/wiki/PRKAB1 | 5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.
The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.
Model organisms
Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)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 five tests were carried out on mutant mice and four significant abnormalit |
https://en.wikipedia.org/wiki/PRKAR2B | cAMP-dependent protein kinase type II-beta regulatory subunit is an enzyme that in humans is encoded by the PRKAR2B gene.
Function
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol.
Interactions
PRKAR2B has been shown to interact with AKAP11 in an advanced Stage.
References
Further reading |
https://en.wikipedia.org/wiki/PSME2 | Proteasome activator complex subunit 2 is a protein that in humans is encoded by the PSME2 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the beta subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three beta and three alpha subunits combine to form a heterohexameric ring. Six pseudogenes have been identified on chromosomes 4, 5, 8, 10 and 13.
Interactions
PSME2 has been shown to interact with PSME1.
References
Further reading |
https://en.wikipedia.org/wiki/UBTF | Upstream binding transcription factor (UBTF), or upstream binding factor (UBF), is a protein that in humans is encoded by the UBTF gene.
Gene
In humans, the UBTF gene encodes a 764 amino acid protein and is located on chromosome 17 at position q21.31. In mice, UBTF is found on chromosome 11 .
Structure
UBTF contains six high mobility group boxes (HMG-boxes) that allow it to bind to DNA. UBTF also contains a hyperacidic carboxy-terminal domain, which is required for transcription activation, and a helix-gap-helix dimersation motif (as UBTF is thought to often act as a dimer).
In humans, alternative splicing can give rise to either the UBTF1 or UBTF2 isoform which are 97 kD and 94 kD in mass, respectively UBTF2 lacks exon 8 of the larger UBTF1 isoform which encodes a portion of HMG Box 2.
Function
UBTF is a transcription factor required for expression of the 18S, 5.8S, and 28S ribosomal RNAs, along with SL1 (a complex of TBP (MIM 600075) and three TBP-associated factors or 'TAFs').
UBTF is a nucleolar phosphoprotein with both DNA binding and transactivation domains. Sequence-specific DNA binding to the core and upstream control elements of the human rRNA promoter is mediated through several HMG boxes. [supplied by OMIM]
In vertebrates, UBTF plays a crucial role in maintaining rDNA chromatin in a euchromatic state. Consequently, UBTF binding is one of the characteristics of euchromatic, transcriptionally active rDNA repeats.
UBTF2 has been found to regulate mRNA |
https://en.wikipedia.org/wiki/AKR1C3 | Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.
Function
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin D2, prostaglandin H2, and phenanthrenequinone, and the oxidation of prostaglandin F2α to prostaglandin D2. It is also capable of metabolizing estrogen and progesterone.
AKR1C3 may play an important role in the development of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.
Pathology
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.
References
External links
Further reading
EC 1.1.1 |
https://en.wikipedia.org/wiki/DYNLL1 | Dynein light chain 1, cytoplasmic is a protein that in humans is encoded by the DYNLL1 gene.
Function
Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed primarily from dynein heavy chains, and stalks linking the heads to a basal domain, which contains a varying number of accessory intermediate chains. The complex is involved in intracellular transport and motility. The protein described in this record is a light chain and exists as part of this complex but also physically interacts with and inhibits the activity of neuronal nitric oxide synthase. Binding of this protein destabilizes the neuronal nitric oxide synthase dimer, a conformation necessary for activity, and it may regulate numerous biologic processes through its effects on nitric oxide synthase activity. Alternate transcriptional splice variants have been characterized.
Interactions
DYNLL1 has been shown to interact with:
BCL2L11,
DLG4
DLGAP1,
DYNC1I1,
IκBα,
MYO5A,
NRF1,
PAK1, and
TP53BP1.
References
Further reading
External links |
https://en.wikipedia.org/wiki/APRIL%20%28protein%29 | A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI. It is encoded by the TNFSF13 gene.
Nomenclature
In the cluster of differentiation terminology, APRIL is designated CD256.
Function
The protein encoded by this gene is a member of the tumor necrosis factor ligand (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vivo experiments suggest an important role for APRIL in the long-term survival of plasma cells in the bone marrow. Mice deficient in APRIL have normal immune system development. However, APRIL-deficient mice have also been reported to possess a reduced ability to support plasma cell survival. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.
Interactions
TNFSF13 has been shown to interact with TNFRSF13B and B-cell activating factor.
Clinical significance
APRIL is being explored as a target for autoimmune diseases and B cell malignancies. At least one anti-APRIL monoclonal antibody has been announced to enter phase I clinical trials for mu |
https://en.wikipedia.org/wiki/RIPK2 | Receptor-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the RIPK2 gene.
This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-κB and inducer of apoptosis in response to various stimuli.
Interactions
RIPK2 has been shown to interact with BIRC2.
References
Further reading |
https://en.wikipedia.org/wiki/MAP3K14 | Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.
Function
This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-κB activity. It is a critical kinase of the alternative NF-κB activation pathway. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-κB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor.
Interactions
MAP3K14 has been shown to interact with:
CHUK,
IKK2, and
TRAF2.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/STUB1 | STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein).
Function
The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the chaperone proteins HSC70 and HSP70 and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle. In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation, mainly of chaperone-bound misfolded proteins.
CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.
Mutations in STUB1 cause spinocerebellarataxiatype 16.
Interactions
STUB1 has been shown to interact with:
C-Raf,
DNAJB1,
HSPA1A,
HSPA4,
HSPA8,
Parkin (ligase), and
RUNX2.
References
Further reading
External links |
https://en.wikipedia.org/wiki/DKK1 | Dickkopf-related protein 1 is a protein that in humans is encoded by the DKK1 gene.
Function
This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the Wnt signaling pathway. Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) is a protein-coding gene that acts from the anterior visceral endoderm. The dickkopf protein encoded by DKK1 is an antagonist of the Wnt/β-catenin signalling pathway that acts by isolating the LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway. DKK1 was also demonstrated to antagonize the Wnt/β-catenin pathway via a reduction in β-catenin and an increase in OCT4 expression.
This inhibition plays a key role in heart, head and forelimb development during anterior morphogenesis of the embryo.
Interactions
DKK1 has been shown to interact with LRP6 and is a high affinity ligand of Kremen proteins.
Clinical significance
Elevated levels of DKK1 in bone marrow, plasma and peripheral blood are associated with the presence of osteolytic bone lesions in patients with multiple myeloma. Due to the role of DKK1 in inflammation induced bone loss DKK1 is under investigation as target for therapeutic strategies in medicine and dentistry.
Animal studies
Scientists have created a DKK1 knockout model in mice that revealed the effects of this gene. All mice that were homozygous for the DKK1 knockout |
https://en.wikipedia.org/wiki/WWOX | WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.
Function
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 2 WW domains and a short-chain dehydrogenase/reductase domain (SRD). The highest normal expression of this gene is detected in hormonally regulated tissues such as testis, ovary, and prostate. This expression pattern and the presence of an SRD domain suggest a role for this gene in steroid metabolism. The encoded protein is more than 90% identical to the mouse protein, which is an essential mediator of tumor necrosis factor-alpha-induced apoptosis, suggesting a similar, important role in apoptosis for the human protein. In addition, there is evidence that this gene behaves as a suppressor of tumor growth. Alternative splicing of this gene generates transcript variants that encode different isoforms.
WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.
Interactions
WWOX has been shown to interact with P53 and ACK1.
References
Further reading |
https://en.wikipedia.org/wiki/CD244 | CD244 (Cluster of Differentiation 244) also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.
CD244 is a type-I transmembrane protein belonging to the signaling lymphocytic activation molecule family of receptors (SLAMF) which are expressed in different types of hematopoietic cells. CD244 plays a role in the regulation of the immune system.
A ligand of CD244 is CD48 (SLAMF2). CD48 also belongs to the SLAMF, it does not have an intracellular domain and it is anchored to the plasma membrane by a GPI-anchor. Only these two receptors from the SLAMF mediate heterophilic interactions.
Gene
The receptor CD244 is encoded by the CD244 gene located on the long arm of human chromosome 1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. CD244 was first described in NK cells but it is also expressed in monocytes, basophils, eosinophils, mast cells, dendritic cells, and T cells.
Structure
The receptor is composed of intracellular, transmembrane, and extracellular domains. The intracellular domain contains four intracellular tyrosine-based switch motives (ITSMs) and interacts with SH2 domain-containing proteins which are involved in the signaling and determine whether it will be activating or inhibitory. The extracellular region of the receptor is composed of one Ig variable-like domain and one Ig constant 2-like domain.
Function
CD244 can function as an activating or inhibitory receptor. The express |
https://en.wikipedia.org/wiki/ACTA2 | ACTA2 (actin alpha 2) is an actin protein with several aliases including alpha-actin, alpha-actin-2, aortic smooth muscle or alpha smooth muscle actin (α-SMA, SMactin, alpha-SM-actin, ASMA). Actins are a family of globular multi-functional proteins that form microfilaments. ACTA2 is one of 6 different actin isoforms and is involved in the contractile apparatus of smooth muscle. ACTA2 (as with all the actins) is extremely highly conserved and found in nearly all mammals.
In humans, ACTA2 is encoded by the ACTA2 gene located on 10q22-q24. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, Moyamoya disease, and multisystemic smooth muscle dysfunction syndrome.
ACTA2 (commonly referred to as alpha-smooth muscle actin or α-SMA) is often used as a marker of myofibroblast formation. Studies have shown that ACTA2 is associated with TGF-β pathway that enhances contractile properties of hepatic stellate cells leading to liver fibrosis and cirrhosis.
References
Further reading
External links
GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections
Human proteins |
https://en.wikipedia.org/wiki/RhoC | RhoC (Ras homolog gene family, member C) is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.
Mechanism and function
It is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. It cycles between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades.
Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape and motility. RhoC can activate formins such as mDia1 and FMNL2 to remodel the cytoskeleton.
Overexpression of RhoC is associated with cell proliferation and causing tumors to become malignant. It causes degradation and reconstruction of the Extracellular Matrix (ECM) which helps cells escape the tissue they are currently in. It enhances cell motility giving it the ability to become invasive. It has been found to have a direct relationship to advanced tumor stage and metastasis, with increases in stage being related to increases in RhoC expression. RhoC-deficient mice can still develop tumors but these fail to metastasize, arguing that RhoC is essential for metastasis.
It has also been found to enhance the creation of angiogenic factors such as VEGF, which is necessary for a tumor to become malignant.
In a study by Vega, RhoC was knocked out which resulted in cells spreading out wide i |
https://en.wikipedia.org/wiki/CHI3L1 | Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted glycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1 gene. The name YKL-40 is derived from the three N-terminal amino acids present on the secreted form and its molecular mass. YKL-40 is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas and asthma.
Function
Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling. YKL-40 lacks chitinase activity due to mutations within the active site (conserved sequence: DXXDXDXE; YKL-40 sequence: DGLDLAWL).
Regulation and mechanism
YKL-40 has been linked to activation of the AKT pro-survival (anti-apoptotic) signaling pathw |
https://en.wikipedia.org/wiki/CTAG1B | Cancer/testis antigen 1 also known as LAGE2 or LAGE2B is a protein that in humans is encoded by the CTAG1B gene. It is most often referenced by its alias NY-ESO-1.
Cancer/Testis Antigen 1B is a protein belonging to the family of Cancer Testis Antigens (CTA) that are expressed in a variety of malignant tumours at the mRNA and protein levels, but also restricted to testicular germ cells in normal adult tissues. A clone of CTAG gene was originally identified by immunological methods in oesophageal carcinoma using patient serum. The aberrant re-expression of CTAs is induced by molecular mechanisms including DNA demethylation, histone post-translational modification, and microRNA-mediated regulation. The effect of DNA demethylation is evident by the capability of demethylating agents, such as 5-aza-2-deoxycytidine, to induce CTAs re-expression in tumour cells but not in normal epithelial cells.
Gene
CTAG1B is located on the long arm of chromosome X (Xq28), containing three exons that are approximately 8 Kb in length. CTAG1B is found to have a neighbouring gene of identical sequence: CTAG1A.
Protein
The gene encodes a 180-amino acid polypeptide, expressed from 18 weeks during embryonic development until birth in human fetal testis. It is also strongly expressed in spermatogonia and in primary spermatocytes of adult testis, but not in post-meiotic cells or testicular somatic cells. Structurally, CTAG1B features a glycine-rich N-terminal region, as well as a hydrophobic C-termin |
https://en.wikipedia.org/wiki/DDB1 | DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.
Gene
The gene's position is on chromosome 11q12-q13.
Protein
The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small (DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa.
Function
As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs). These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling (Cdt2) and more.
Interactions
DDB1 has been shown to interact with Transcription initiation protein SPT3 homolog, GCN5L2, DDB2, CUL4A, CUL4B and P21.
References
Further reading |
https://en.wikipedia.org/wiki/Ephrin%20A1 | Ephrin A1 is a protein that in humans is encoded by the EFNA1 gene.
This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. 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. This gene encodes an EFNA class ephrin which binds to the EPHA2, EPHA4, EPHA5, EPHA6, and EPHA7 receptors. Two transcript variants that encode different isoforms were identified through sequence analysis.
Model organisms
Model organisms have been used in the study of EFNA1 function. A conditional knockout mouse line, called Efna1tm1a(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 four tests were carried out on homozygous mutant mice and one significant abnormality was observed: a transformation in vertebral number from lumbar vertebrae to sacral vertebrae.
References
Further reading
Genes mu |
https://en.wikipedia.org/wiki/HLA-DMA | HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.
HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail.
References
Further reading
MHC class II |
https://en.wikipedia.org/wiki/Neutrophil%20cytosolic%20factor%204 | Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.
Function
The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
Clinical significance
GWAS studies showed that Crohn's disease patient with certain SNPs in NCF4 are more susceptible to get Crohn's disease. Crohn's patient with rs4821544 variants showed a decreased reactive oxygen species after stimulation with GM-CSF which is a proinflammtory cytokine.
Interactions
Neutrophil cytosolic factor 4 has been shown to interact with Ku70, Neutrophil cytosolic factor 1 and Moesin.
References
Further reading
|
https://en.wikipedia.org/wiki/Peroxiredoxin%201 | Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.
Function
This gene 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. Three transcript variants encoding the same protein have been identified for this gene.
Interactions
Peroxiredoxin 1 has been shown to interact with PRDX4. A chemoproteomic approach has revealed that peroxiredoxin 1 is the main target of theonellasterone.
Clinical significance
As enzymes that combat oxidative stress, peroxiredoxins play an important role in health and disease. Peroxiredoxin 1 and peroxiredoxin 2 have been shown to be released by some cells when stimulated by LPS or TNF-alpha. The released peroxiredoxin can then act to produce inflammatory cytokines. The levels of peroxiredoxin 1 are elevated in pancreatic cancer and it can potentially act as a marker for the diagnosis and prognosis of this disease. In some types of cancer, peroxiredoxin 1 has been determined to act as a tumor suppressor and other studies show that peroxiredoxin 1 is overexpressed in certain human cancers. A recent study has found that peroxiredoxin 1 may play a role in tumorigenesis by regulating the mTOR/p70S6K pathway in esophageal squamo |
https://en.wikipedia.org/wiki/PAX5 | Paired box protein Pax-5 is a protein that in humans is encoded by the PAX5 gene.
Function
The PAX5 gene is a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly conserved DNA-binding domain, known as the paired box. The PAX proteins are important regulators in early development, and alterations in the expression of their genes are thought to contribute to neoplastic transformation. The PAX5 gene encodes the B-cell lineage specific activator protein (BSAP) that is expressed at early, but not late stages of B-cell differentiation. Its expression has also been detected in developing CNS and testis, therefore, PAX5 gene product may not only play an important role in B-cell differentiation, but also in neural development and spermatogenesis.
Clinical significance
The PAX5 gene is located in chromosome 9p13 region, which is involved in t(9;14)(p13;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype, and in derived large-cell lymphomas. This translocation brings the potent E-mu enhancer of the IgH gene locus into close proximity of the PAX5 promoters, suggesting that the deregulation of PAX5 gene transcription contributes to the pathogenesis of these lymphomas.
Up to 97% of the Reed–Sternberg cells of Hodgkin's lymphoma express Pax-5.
Interactions
PAX5 has been shown to interact with TLE4 and Death associated protein 6.
See also
Pax genes
References
Furthe |
https://en.wikipedia.org/wiki/MAP2K7 | Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini (α, β, and γ isoforms) and two possible C-termini (1 and 2 isoforms).
MKK7 is involved in signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK5, and MAP4K2/GCK.
MKK7 is ubiquitously expressed in all tissue. However, it displays a higher level of expression in skeletal muscle. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found.
Nomenclature
MAP2K7 is also known as:
MKK7
JNK-activated kinase 2
MAPK/ERK kinase 7 (MEK7)
Stress-activated protein kinase kinase 4 (SAPK kinase 4, SAPKK4)
c-Jun N-terminal kinase kinase 2 (JNK kinase 2, JNKK2)
Stress-activated / extracellular signal-regulated protein kinase kinase 2 (SEK2)
Isoforms
The murine MKK7 protein is encoded by 14 exons which can be alternatively spliced to yield a group of protein kinases. This results in six isoforms with three possible N-termini (α, β, and γ isoforms) and two possible C-termini (1 and 2 iso |
https://en.wikipedia.org/wiki/RE1-silencing%20transcription%20factor | RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST gene, and acts as a transcriptional repressor. REST is expressly involved in the repression of neural genes in non-neuronal cells. Many genetic disorders have been tied to alterations in the REST expression pattern, including colon and small-cell lung carcinomas found with truncated versions of REST. In addition to these cancers, defects in REST have also been attributed a role in Huntington Disease, neuroblastomas, and the effects of epileptic seizures and ischemia.
Function
This gene encodes a transcriptional repressor which represses neuronal genes in non-neuronal tissues. It is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element (NRSE, also known as RE1). The protein is also found in undifferentiated neuronal progenitor cells, and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described; however, their full length nature has not been determined. REST is found to be down-regulated in elderly people with Alzheimer's disease.
REST contains 8 Cys2His2 zinc fingers and mediates gene repression by recruiting several chromatin-modifying enzymes.
REST expression strongly correlates with increased longevity. |
https://en.wikipedia.org/wiki/SFPQ | Splicing factor, proline- and glutamine-rich is a protein that in humans is encoded by the SFPQ gene.
Interactions
SFPQ has been shown to interact with PTBP1, NONO, CDC5L and Ubiquitin C.
References
Further reading |
https://en.wikipedia.org/wiki/TAF9 | TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the TAF9 gene.
Function
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein complex that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the smaller subunits of TFIID that binds to the basal transcription factor GTF2B as well as to several transcriptional activators such as p53 and VP16. A similar but distinct gene (TAF9B) has been found on the X chromosome and a pseudogene has been identified on chromosome 19. Alternative splicing results in multiple transcript variants encoding different isoforms.
Structure
The 17-amino-acid-long trans-activating domains (TAD) of several transcription factors were reported to bind directly to TAF9: p53, VP16, HSF1, NF-IL6, NFAT1, NF-κB, and ALL1/MLL1. I |
https://en.wikipedia.org/wiki/U2%20small%20nuclear%20RNA%20auxiliary%20factor%201 | Splicing factor U2AF 35 kDa subunit is a protein that in humans is encoded by the U2AF1 gene.
Function
This gene belongs to the splicing factor SR family of genes . U2AF1 is a subunit of the U2 Auxiliary Factor complex alongside a larger subunit, U2AF2. U2AF1 is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes a small (~35 kDa) subunit which plays a critical role in RNA splicing by recognizing and binding to AG nucleotides at the 3’ splice site to facilitate spliceosome assembly. Alternatively spliced transcript variants encoding different isoforms have been identified . Somatic mutations in U2AF1 have been found in a range of human cancers, with a distinctive pattern of these mutations at the zinc fingers implicating a functional role under selection. In lung cancers, these mutations affect alternative splicing of several transcripts, including oncogenic ROS1 fusions.
U2af1 conditional deletion in mouse hematopoietic system leads to early lethality suggesting its important for hematopoietic stem cell maintenance and function {https://doi.org/10.1038/s41375-020-01116-x }.
Interactions
U2 small nuclear RNA auxiliary factor 1 has been shown to interact with:
ASF/SF2,
NXF1,
RP9,
SMNDC1,
U2AF2, and
ZRANB2.
References
Further reading
External links |
https://en.wikipedia.org/wiki/LIGHT%20%28protein%29 | LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.
Nomenclature
LIGHT stands for "homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes". In the cluster of differentiation terminology it is classified as CD258.
Function
The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). Two alternatively spliced transcript variant encoding distinct isoforms have been reported.
This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, trigger apoptosis of various tumor cells and play a role in vascular normalisation processes. This protein is also reported to prevent tumor necrosis factor alpha-mediated apoptosis in primary hepatocytes.
Interactions
LIGHT has been shown to interact with TNFRSF14, TNFRSF6B, BIRC2, TRAF2 and TRAF3.
Role in herpes simplex virus
Similar to how CD4 is the primary mediating receptor in HIV infection, the HSV glycoprotein (gD) |
https://en.wikipedia.org/wiki/PSMF1 | Proteasome inhibitor PI31 subunit is a protein that in humans is encoded by the PSMF1 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 protein that inhibits the activation of the proteasome by the 11S and 19S regulators. Alternative transcript variants have been identified for this gene.
References
Further reading |
https://en.wikipedia.org/wiki/ABCG1 | ATP-binding cassette sub-family G member 1 is a protein that in humans is encoded by the ABCG1 gene. It is a homolog of the well-known Drosophila gene white.
Function
The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily (subfamily G). It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Several alternative splice variants have been identified.
See also
ATP-binding cassette transporter
References
Further reading
External links
ATP-binding cassette transporters |
https://en.wikipedia.org/wiki/Histone%20deacetylase%205 | Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.
Function
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene.
AMP-activated protein kinase regulation of the glucose transporter GLUT4 occurs by phosphorylation of HDAC5.
HDAC5 is involved in memory consolidation and suggests that development of more selective HDAC inhibitors for the treatment of Alzheimer's disease should avoid targeting HDAC5. Its function can be effectively examined by siRNA knockdown based on an independent validation.
HDAC5 overexpression in urothelial carcinoma cell lines inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition (EMT)
Interactions
Histone deacetylase 5 has been shown to interact with:
BCL6,
CBX5,
GATA1,
HDAC3,
IKZF1, |
https://en.wikipedia.org/wiki/Syncytin-1 | Syncytin-1 also known as enverin is a protein found in humans and other primates that is encoded by the ERVW-1 gene (endogenous retrovirus group W envelope member 1). Syncytin-1 is a cell-cell fusion protein whose function is best characterized in placental development. The placenta in turn aids in embryo attachment to the uterus and establishment of a nutrient supply.
The gene encoding this protein is an endogenous retroviral element that is the remnant of an ancient retroviral infection integrated into the primate germ line. In the case of syncytin-1 (which is found in humans, apes, and Old World but not New World monkeys), this integration likely occurred more than 25 million years ago. Syncytin-1 is one of two known syncytin proteins expressed in catarrhini primates (the other being syncytin-2) and one of many viral genomes incorporated on multiple occasions over evolutionary time in diverse mammalian species.
ERVW-1 is located within ERVWE1, a full length provirus on chromosome 7 at locus 7q21.2 flanked by long terminal repeats (LTRs) and is preceded by ERVW1 gag (Group AntiGen) and pol (POLymerase) within the provirus, both of which contain nonsense mutations rendering them non-coding.
Syncytin-1 is also implicated in a number of neurological pathologies, most notably, multiple sclerosis, as an immunogen.
Placental development
Syncytin-1 mediated trophoblast fusion is essential for normal placental development. The early placental barrier is composed of two place |
https://en.wikipedia.org/wiki/PRKAG2 | 5'-AMP-activated protein kinase subunit gamma-2 is an enzyme that in humans is encoded by the PRKAG2 gene.
Function
AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family and encodes a protein with four CBS domains. Mutations in this gene have been associated with ventricular pre-excitation (Wolff–Parkinson–White syndrome), progressive conduction system disease and cardiac hypertrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
Interactions
PRKAG2 has been shown to interact with PRKAB2 and PRKAB1.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Familial Hypertrophic Cardiomyopathy Overview
EC 2.7.11 |
https://en.wikipedia.org/wiki/FBXW7 | F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.
Function
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and mul |
https://en.wikipedia.org/wiki/Azurocidin%201 | Azurocidin also known as cationic antimicrobial protein CAP37 or heparin-binding protein (HBP) is a protein that in humans is encoded by the AZU1 gene.
Function
Azurophil granules, specialized lysosomes of the neutrophil, contain at least 10 proteins implicated in the killing of microorganisms. The protein encoded by this gene is an azurophil granule antimicrobial protein, with monocyte chemotactic and antibacterial activity. It is also an important multifunctional inflammatory mediator. The genes encoding this protein, neutrophil elastase 2, and proteinase 3 are in a cluster located at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.
Structure
This encoded protein is a member of the PA clan of proteases but it is not a serine proteinase, because the active site serine and histidine residues are replaced, making it a pseudoenzyme.
Clinical significance
In patients with fever, high plasma levels of HBP indicates that the patient is at high risk of developing sepsis with circulatory collapse.
References
External links
Further reading |
https://en.wikipedia.org/wiki/KRIT1 | Krev interaction trapped protein 1 or Cerebral cavernous malformations 1 protein is a protein that in humans is encoded by the KRIT1 gene. This gene contains 16 coding exons and is located on chromosome 7q21.2. Loss of function mutations in KRIT1 result in the onset of cerebral cavernous malformation. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
Interactions
The KRIT1 protein, is 736 amino acids in length and has a variety of functions. KRIT1 has been shown to interact with multiple signaling pathways including; ITGB1BP1., reactive oxygen species, cell death, and angiogenesis. Related to cerebral cavernous malformations, this protein is required for maintaining the structural integrity of the vasculature.
References
Further reading |
https://en.wikipedia.org/wiki/Collagen%2C%20type%20VI%2C%20alpha%201 | Collagen alpha-1(VI) chain is a protein that in humans is encoded by the COL6A1 gene.
Function
The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview |
https://en.wikipedia.org/wiki/Cystatin%20B | Cystatin-B is a protein that in humans is encoded by the CSTB gene.
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and kininogens. This gene encodes a stefin that functions as an intracellular cysteine protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins L, H and B. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with Unverricht–Lundborg disease, a form of progressive myoclonic epilepsy (EPM1).
Interactions
Cystatin B has been shown to interact with Cathepsin B.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Unverricht-Lundborg Disease or EPM1
The MEROPS online database for peptidases and their inhibitors: I25.003
PDBe-KB provides an overview of all the structure information available in the PDB for Human Cystatin-B |
https://en.wikipedia.org/wiki/Homeobox%20protein%20Nkx-2.5 | Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.
Function
Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is expressed in the developing dorsal vessel and in the equivalent of the vertebrate heart. Mutations in tinman result in loss of heart formation in the embryo, suggesting that tinman is essential for Drosophila heart formation. Furthermore, abundant expression of Csx, the presumptive mouse homolog of tinman, is observed only in the heart from the time of cardiac differentiation. CSX, the human homolog of murine Csx, has a homeodomain sequence identical to that of Csx and is expressed only in the heart, again suggesting that CSX plays an important role in human heart formation.
In humans, proper NKX2-5 expression is essential for the development of atrial, ventricular, and conotruncal septation, atrioventricular (AV) valve formation, and maintenance of AV conduction. Mutations in expression are associated with congenital heart disease (CHD) and related ailments. Patients with NKX2-5 mutations commonly present AV conduction block and atrial septal defects (ASD). Recently, postnatal roles of cardiac transcription factors have been extensively investigated. Consistent with the d |
https://en.wikipedia.org/wiki/Dyskerin | H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.
This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.
Clinical significance
Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita
Telomere-related genes
Telomere-related proteins |
https://en.wikipedia.org/wiki/EXT1 | Exostosin-1 is a protein that in humans is encoded by the EXT1 gene.
This gene encodes one of the two endoplasmic reticulum-resident type II transmembrane glycosyltransferase – the other being EXT2 – which are involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses.
Interactions
EXT1 has been shown to interact with TRAP1.
See also
Langer–Giedion syndrome
Hereditary multiple exostoses type 1
References
Further reading
External links
Multiple Hereditary Exostoses Research Foundation |
https://en.wikipedia.org/wiki/GCLC | Glutamate—cysteine ligase catalytic subunit is an enzyme that in humans is encoded by the GCLC gene.
Function
Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. The gene encoding the catalytic subunit encodes a protein of 367 amino acids with a calculated molecular weight of 72.773 kDa and maps to chromosome 6. The regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Deficiency of gamma-glutamylcysteine synthetase in human is associated with enzymopathic hemolytic anemia.
Model organisms
Model organisms have been used in the study of GCLC function. A conditional knockout mouse line, called Gclctm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice, however no significant abnormalities were observed.
References
Further reading
Genes mutated in mice |
https://en.wikipedia.org/wiki/GRIA2 | Glutamate ionotropic receptor AMPA type subunit 2 (Glutamate receptor 2, or GluR-2) is a protein that in humans is encoded by the GRIA2 (or GLUR2) gene and it is a subunit found in the AMPA receptors.
Function
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), called AMPA receptors, and function as ligand-activated cation channels. These channels are assembled from a combination of 4 subunits, encoded by 4 genes (GRIA1-4). The subunit encoded by this gene (GRIA2) is subject to RNA editing which renders the receptor that it becomes part of impermeable to calcium ions (Ca2+). Human and animal studies suggest that the RNA editing is essential for normal brain function, and defective RNA editing of this gene may be relevant to the etiology of amyotrophic lateral sclerosis (ALS). Alternative splicing, resulting in transcript variants encoding different isoforms, has been noted for this gene, which includes the generation of flip and flop isoforms that vary in their signal transduction properties.
Interactions
GRIA2 has been shown to interact with SPTAN1, GRIP1 and PICK1.
RNA editing
Several ion channels and neurotransmitters receptors pre-mRNA as substrates for ADARs. This includes 5 subunits of the glutamate rece |
https://en.wikipedia.org/wiki/Integrin%20beta%206 | Integrin beta-6 is a protein that in humans is encoded by the ITGB6 gene. It is the β6 subunit of the integrin αvβ6. Integrins are αβ heterodimeric glycoproteins which span the cell’s membrane, integrating the outside and inside of the cell. Integrins bind to specific extracellular proteins in the extracellular matrix or on other cells and subsequently transduce signals intracellularly to affect cell behaviour. One α and one β subunit associate non-covalently to form 24 unique integrins found in mammals. While some β integrin subunits partner with multiple α subunits, β6 associates exclusively with the αv subunit. Thus, the function of ITGB6 is entirely associated with the integrin αvβ6.
Discovery
The β6 subunit and ITGB6 sequence was discovered by Professor Dean Sheppard and colleagues at the University of California, San Francisco in the early 1990s in guinea pig cells. Further investigation by research groups from the University of Madrid and University of Auckland found that ITGB6 was located on chromosome 2q at position 24.2.
In the past decade, significant research has been performed toward identifying the location of regions within the ITGB6 gene which both promote and suppress ITGB6 expression. Of note, binding regions for transcription factors STAT3 and C/EBPα were found, and basic normal cell expression of ITGB6 is thought to be regulated primarily by these proteins. Other transcription factors such as Ets-1 and Smad3 have also been shown to increase ITGB6 expres |
https://en.wikipedia.org/wiki/Involucrin | Involucrin is a protein component of human skin and in humans is encoded by the IVL gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin.
Gene
This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin.
Function
Involucrin is a highly reactive, soluble, transglutaminase substrate protein present in keratinocytes of epidermis and other stratified squamous epithelia. It first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase thus helping in the formation of an insoluble envelope beneath the plasma membrane functioning as a glutamyl donor during assembly of the cornified envelope.
Involucrin is synthesised in the stratum spinosum and cross linked in the stratum granulosum by the transglutaminase enzyme that makes it highly stable. Thus it provides structural support to the cell, thereby allowing the cell to resist invasion by micro-organisms.
Apigenin, a plant-derived flavanoid that has significant promise as a skin cancer chemopreventive agent, has been found to regulate normal human keratinocyte differentiation by suppressing involucrin, and this is associated with reduced cell proliferation without apoptosis.
Clinical significance
As one of the precursor proteins of the cornified cell envelope, involucrin is markedly increased in inflammatory skin diseases such as psoriasis
L |
https://en.wikipedia.org/wiki/Laminin%2C%20beta%203 | Laminin subunit beta-3 is a protein that in humans is encoded by the LAMB3 gene.
LAMB3 encodes the beta 3 subunit of laminin. Laminin is composed of three subunits (alpha, beta, and gamma), and refers to a family of basement membrane proteins. For example, LAMB3 serves as the beta chain in laminin-5. Mutations in LAMB3 have been identified as the cause of various types of epidermolysis bullosa. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.
References
Further reading
Laminins |
https://en.wikipedia.org/wiki/NEDD9 | Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) is a protein that in humans is encoded by the NEDD9 gene. NEDD-9 is also known as enhancer of filamentation 1 (EF1), CRK-associated substrate-related protein (CAS-L), and Cas scaffolding protein family member 2 (CASS2). An important paralog of this gene is BCAR1.
Discovery
In 1992, Kumar, et al., first described a sequence tag corresponding to the NEDD9 3′ untranslated region based on the cloning of a group of genes predominantly expressed in the brain of embryonic, but not adult mice, a group of genes designated neural precursor cell expressed, developmentally down-regulated. In 1996, two groups independently described the complete sequence of the NEDD9 gene, and provided initial functional analysis of NEDD9 protein. Law et al. overexpressed a human cDNA library in S. cerevisiae, and screened for genes that simultaneously affected cell cycle and cell polarity controls, inducing a filamentous yeast budding phenotype, and thus identified the HEF1 protein (Human Enhancer of Filamentation 1). This study identified HEF1/NEDD9 as an interactive partner for focal adhesion kinase (FAK), connecting it to integrin signaling. Separately, Minegishi et al. cloned the gene encoding a protein hyperphosphorylated following ligation of β1-integrins in T cells and hypothesized to play a role in the process of T cell costimulation, designating this gene Cas-L (Crk-associated substrate-related protein, Lymphocy |
https://en.wikipedia.org/wiki/PSMA5 | Proteasome subunit alpha type-5 also known as 20S proteasome subunit alpha-5 is a protein that in humans is encoded by the PSMA5 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.
Function
The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. As a component of alpha ring, Proteasome subunit alpha type-5 contributes to the formation of heptameric alpha rings and substrate entrance gate.
Structure
Expression
The gene PSMA5 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. The gene has 9 exons and locates at chromosome band 1p13. The human protein proteasome subunit alpha type-5 is 26.5 kDa in size and composed of 241 amino acids. The calculated theoretical pI (isoelectric point) of this protein is 4.69.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed b |
https://en.wikipedia.org/wiki/REG1A | Pancreatic Stone Protein (PSP), also known as Lithostathine-1-alpha islet cells regeneration factor (ICRF) or islet of Langerhans regenerating protein (REG) is a protein that in humans is encoded by the REG1A gene as a single polypeptide of 144 amino acids further cleaved by trypsin to produce a 133 amino acid protein that is O-linked glycosylated on threonine 27. This protein is a type I subclass member of the Regenerating protein family. The Reg protein family is a multi protein family grouped into four subclasses, types I, II, III and IV based on the primary structures of the proteins.
Reg family members REG1B, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication.
The PSP is mostly produced in Human by the acinar cells of the pancreas and is secreted in the duodenum by the same pathway that pancreatic exocrine enzymes. It has C-terminal C-type lectin domain whose binding partner is currently unknown.
Function
Pancreas development and regeneration
The PSP has been shown to be associated with islet cell regeneration and diabetogenesis and may be involved in pancreatic lithogenesis (creation of pancreatic stones; pancreatic calculi).
Sepsis
The blood PSP concentration has been shown to increase substantially in response to a sepsis event. Consequently, the use of the PSP as a biomarker of sepsis has been investigated thoroughly and the result of these researches confirmed the high diagnosti |
https://en.wikipedia.org/wiki/SCNN1G | The SCNN1G gene encodes for the γ subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by SCNN1A, SCNN1B, and SCNN1D.
ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation of action potentials in neurons. The abbreviation for the genes encoding for voltage-gated sodium channel starts with three letters: SCN. In contrast to these sodium channels, ENaC is constitutively active and is not voltage-dependent. The second N in the abbreviation (SCNN1) represents that these are NON-voltage-gated channels.
In most vertebrates, sodium ions are the major determinant of the osmolarity of the extracellular fluid. ENaC allows transfer of sodium ions across the epithelial cell membrane in so-called "tight-epithelia" that have low permeability. The flow of sodium ions across epithelia affects osmolarity of the extracellular fluid. Thus, ENaC plays a central role in the regulation of body fluid and electrolyte homeostasis and consequently affects blood pressure.
As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel".
History
The first cDNA encoding the gamma subunit of ENaC was cloned and sequenced by Canessa et al. from rat mRNA. A year later, two independent groups reported the cDNA sequences of the beta- and gamm |
https://en.wikipedia.org/wiki/TRIM21 | Tripartite motif-containing protein 21, also known as E3 ubiquitin-protein ligase TRIM21, is a protein that in humans is encoded by the TRIM21 gene. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. It is expressed in most human tissues.
Structure
TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING finger domain, a B-box type 1 and a B-box type 2 zinc finger, and a coiled coil region.
Function
TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain and binds to immunoglobulin G, immunoglobulin A and immunoglobulin M on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.
TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus.
Clinical significance
RoSSA interacts with autoantigens in patients with Sjögren's syndrome and systemic lupus erythematosus. In addition, the inability for lupus-prone macrophages to degrade immune complexes in the lysosome results in the leakage of autoan |
https://en.wikipedia.org/wiki/TEC%20%28gene%29 | Tyrosine-protein kinase Tec is a tyrosine kinase that in humans is encoded by the TEC gene. Tec kinase is expressed in hematopoietic, liver, and kidney cells and plays an important role in T-helper cell processes. Tec kinase is the name-giving member of the Tec kinase family, a family of non-receptor protein-tyrosine kinases.
Structure
Tec kinase contains five protein interaction domains. The characteristic feature of Tec family kinases is a pleckstrin homology (PH) domain on the N-terminus of the molecule followed by a Tec homology (TH) domain. The TH domain of Tec kinase contains a Btk homology (BH) motif and two proline-rich (PR) regions. The other protein interaction domains of Tec kinase include Src homology (SH) domains SH2 and SH3 and a kinase domain with enzymatic activity.
TEC produces two protein isoforms that differ in the SH3 domain through alternative splicing. Type IV isoform has a full length SH3 domain and is predominately expressed in hematopoietic cells. Type III isoform has a SH3 domain that lacks the COOH-terminal 22 residues and is predominately expressed in the liver and kidney. It is likely the shortened SH3 domain of type III Tec kinase is a disabled form.
TEC resides on chromosome 4, locus 4p12 in humans. TEC is located only 1.5kb away from TXK, another member of the Tec kinase family, making it likely these two kinase genes arose through the process of gene-duplication.
Function
Functions of Tec family kinases
Tec family kinases are involved i |
https://en.wikipedia.org/wiki/Trefoil%20factor%203 | Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene.
Function
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 disulfide bonds. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are diverse, including protection of the mucosa, thickening of the mucus, and increasing epithelial healing rates. This gene is a marker of columnar epithelium and is expressed in a variety of tissues including goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.
Glycan binding
All three 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.
In breast milk
Trefoil factors (TFF) are secretory products of mucin producing cells. They play a key role in the maintenance of the surface integrity of oral mucosa and enhance healing of the gastrointestinal mucosa by a process called restitution. TFF comprises the gastric peptides (TFF1), spasmolytic peptide (TFF2), and the intestinal trefoil factor (TFF3, this prote |
https://en.wikipedia.org/wiki/RPS6KA5 | Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.
Interactions
RPS6KA5 has been shown to interact with CREB1.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/IKZF1 | DNA-binding protein Ikaros also known as Ikaros family zinc finger protein 1 is a protein that in humans is encoded by the IKZF1 gene.
Ikaros - transcription factor
Ikaros is a transcription factor that is encoded by the IKZF genes of the Ikaros family zinc finger group. Zinc finger is a small structural motif of protein that allows protein binding to DNA or RNA molecule that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold.
Ikaros displays crucial functions in the hematopoietic system and is a known regulator of immune cells development, mainly in early B cells, CD4+ T cells. Its dysfunction has been linked to the development of chronic lymphocytic leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia and that it also has a part in the differentiation and function of individual T helper cells.
Ikaros also has a role during the later stages of B cell development during VDJ recombination in switch class of the antibody isotypes and expression of the B cell receptor.
In Ikaros knockout mice, T cells but not B cells are generated late in mouse development due to late compensatory expression of the related gene Aiolos (IKZF3). Ikaros point mutant mice are embryonic lethal due to anemia; they have severe defects in terminal erythrocyte and granulocyte differentiation, and excessive macrophage formation. SNPs located near the 3' regio |
https://en.wikipedia.org/wiki/PSIP1 | PC4 and SFRS1 interacting protein 1, also known as lens epithelium-derived growth factor (LEDGF/p75), dense fine speckles 70kD protein (DFS 70) or transcriptional coactivator p75/p52, is a protein that in humans is encoded by the PSIP1 gene.
Function
PSIP1 has not been clearly linked to a specific cellular mechanism. The term LEDGF/p75 (Lens epithelium-derived growth factor) has entered common usage based on the initial characterization of PSIP1, however this is a misnomer, as the protein is present in most tissues and has no direct role in the development of lens epithelium. LEDGF/p75, a transcription coactivator, gained prominence as a host factor that assists HIV integration and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels. The interaction between HIV integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery. LEDGF/p75 recruits MLL complexes to HOX genes to regulate their expression. LEDGF/p52 is shown to recruit splicing factors to H3K36 trimethylated chromatin to modulate alternative splicing, also regulates HOTTIP lncRNA, which is shown to regulate HOX genes in cis.
Structure
LEDGF/p75 is a 60kDa, 530-amino-acid-long protein. The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the AT-hook DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase-binding domain, which interacts with |
https://en.wikipedia.org/wiki/Cell%20adhesion%20molecule%201 | Cell adhesion molecule 1 is a protein that, in humans, is encoded by the CADM1 gene.
Model organisms
Model organisms have been used in the study of CADM1 function. A conditional knockout mouse line, called Cadm1tm1.2Brd was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on homozygous mutant mice and one significant abnormality was observed: males were infertile. Further analysis showed spermatogenesis had arrested in these mice.
Interactions
Cell adhesion molecule 1 has been shown to interact with EPB41L3.
Association studies
Genome-wide association studies identified an association between body mass index and two loci near the CADM1 and CADM2 gene. Experimental results of another study showed that obese mice had an over expression of both CADM1 and CADM2 genes, and that loss of CADM1 protected mice from obesity, promoting a negative energy balance and weight loss.
Furthermore, a 2019 GWAS study revealed an association between Anorexia nervosa and CADM1.
In the brain, this genes mediate synaptic assembly, and mutations in CADM1 are also associated with Autistic spectrum disorder.
See also
Cell adhesion molecule
Nectin
References
Further reading
Genes mutated in mice |
https://en.wikipedia.org/wiki/Laminin%20subunit%20alpha-1 | Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene.
Interactions
Laminin, alpha 1 has been shown to interact with FBLN2.
Role in pathology
Mutations of the LAMA1 gene cause the Poretti–Boltshauser syndrome.
References
Further reading
Laminins |
https://en.wikipedia.org/wiki/DFFA | DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in humans is encoded by the DFFA gene.
Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
The C-terminal domain of DFFA (DFF-C) consists of four alpha-helices, which are folded in a helix-packing arrangement, with alpha-2 and alpha-3 packing against a long C-terminal helix (alpha-4). The main function of this domain is the inhibition of DFFB by binding to its C-terminal catalytic domain through ionic interactions, thereby inhibiting the fragmentation of DNA in the apoptotic process. In addition to blocking the DNase activity of DFFB, the C-terminal region of DFFA is also important for the DFFB-specific folding chaperone activity, a |
https://en.wikipedia.org/wiki/Endothelin%20converting%20enzyme%201 | Endothelin converting enzyme 1, also known as ECE1, is an enzyme which in humans is encoded by the ECE1 gene.
Function
Endothelin-converting enzyme-1 is involved in the proteolytic processing of endothelin-1 (EDN1), -2 (EDN2), and -3 (EDN3) to biologically active peptides.
References
Further reading |
https://en.wikipedia.org/wiki/GLRX | Glutaredoxin-1 is a protein that in humans is encoded by the GLRX gene.
Interactions
GLRX has been shown to interact with Wilson disease protein and ATP7A.
References
Further reading |
https://en.wikipedia.org/wiki/ID3%20%28gene%29 | DNA-binding protein inhibitor ID-3 is a protein that in humans is encoded by the ID3 gene.
Function
Members of the ID family of helix-loop-helix (HLH) proteins lack a basic DNA-binding domain and inhibit transcription through formation of nonfunctional dimers that are incapable of binding to DNA.[supplied by OMIM]
Interactions
ID3 (gene) has been shown to interact with TCF3.
Repressors of ID3
BTG2 binds to the promoter of Id3 and represses its activity. By this mechanism, the upregulation of Id3 in the hippocampus caused by BTG2 ablation prevents terminal differentiation of hippocampal neurons.
See also
Inhibitor of DNA-binding protein
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/KIR3DL1 | Killer cell immunoglobulin-like receptor 3DL1 is a protein that in humans is encoded by the KIR3DL1 gene.
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte immunoglobulin-like receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response.
See also
Cluster of differentiation
References
Further reading
Clusters of differentiation
Immunoglobulin superfamily |
https://en.wikipedia.org/wiki/Laminin%20subunit%20gamma-1 | Laminin subunit gamma-1 is a protein that in humans is encoded by the LAMC1 gene.
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also |
https://en.wikipedia.org/wiki/Epithelial%20cell%20adhesion%20molecule | Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, proliferation, and differentiation. Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc, e-fabp, and cyclins A & E. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker for various cancers. It appears to play a role in tumorigenesis and metastasis of carcinomas, so it can also act as a potential prognostic marker and as a potential target for immunotherapeutic strategies.
Expression pattern
First discovered in 1979, EpCAM was initially described as a dominant surface antigen on human colon carcinoma. Because of its prevalence on many carcinomas, it has been "discovered" many different times. EpCAM therefore has many aliases the most notable of which include TACSTD1 (tumor-associated calcium signal transducer 1), CD326 (cluster of differentiation 326), and the 17-1A antigen.
EpCAM expression is not limited to human colon carcinomas; in fact, EpCAM is expressed in a variety of human epithelial tissues, carcinomas, and progenitor and stem cells. However, EpCAM is not found in non-epithelial cells or cancers of non-epithelial origin. EpCAM is expressed on the basolateral membrane of all simple (especially glandular), pseudo-stratified, and transiti |
https://en.wikipedia.org/wiki/Msh%20homeobox%202 | Homeobox protein MSX-2 is a protein that in humans is encoded by the MSX2 gene.
Function
This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2.
Msx2 is a homeobox gene localized on human chromosome 5 that encodes a transcription repressor and activator (MSX-2) responsible for craniofacial and limb-bud development. Cells will express msx2 when exposed to signaling molecules BMP-2 and BMP-4 in situ. Expression of msx2 leads to the proliferation, migration and osteogenic differentiation of neural crest cells during embryogenesis and bone fracture. It is well documented that expression of cell-cell adhesion molecules such as E-cadherins will promote structural integrity and an epithelial arrangement of cells, while expression of N-cadherin and vimentin promote mesenchymal arrangement and cell migration. Msx2 downregulates E-cadherins and upregulates N-cadherin and vimentin which indicates its role in inducing epithelial mesenchymal transition (EMT). Germline knockout mice have been created for this gene (Msx2 +/-) in |
https://en.wikipedia.org/wiki/Metallothionein%202A | Metallothionein-2 is a metallothionein protein that in humans is encoded by the MT2A gene.
The single-nucleotide polymorphism rs28366003 which substitutes guanine for adenine in MT2A is associated with certain cancers and some chronic diseases.
Interactions
Metallothionein 2A has been shown to interact with protein kinase D1.
References
Further reading
Human proteins |
https://en.wikipedia.org/wiki/Phosphatidylethanolamine%20binding%20protein%201 | Phosphatidylethanolamine-binding protein 1 is a protein that in humans is encoded by the PEBP1 gene.
Interactions
Phosphatidylethanolamine binding protein 1 has been shown to interact with:
C-Raf,
MAP2K1, and
MAPK1.
References
Further reading |
https://en.wikipedia.org/wiki/PSMB7 | Proteasome subunit beta type-7 as known as 20S proteasome subunit beta-2 is a protein that in humans is encoded by the PSMB7 gene.
This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic 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 PSMB7 gene has 8 exons and locates at chromosome band 9q34.11-q34.12.
Protein
The gene PSMB7 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit (beta 2, according to systematic nomenclature) is downregulated by gamma interferon due to an alternatively elevated expression of inducible subunit beta2i, which leads to augmented incorporation of beta2i instead of beta2 into the final assembled 20S com |
https://en.wikipedia.org/wiki/PSMC6 | 26S protease regulatory subunit S10B, also known as 26S proteasome AAA-ATPase subunit Rpt4, is an enzyme that in humans is encoded by the PSMC6 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex Six 26S proteasome AAA-ATPase subunits (Rpt1, Rpt2, Rpt3, Rpt4 (this protein), Rpt5, and Rpt6) together with four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13) form the base sub complex of 19S regulatory particle for proteasome complex.
Gene
The gene PSMC6 encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. Pseudogenes have been identified on chromosomes 8 and 12. The human gene PSMC6 has 15 exons and locates at chromosome band 14q22.1.
Protein
The human protein 26S protease regulatory subunit S10B is 44kDa in size and composed of 389 amino acids. The calculated theoretical pI of this protein is 7.09.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S sub |
https://en.wikipedia.org/wiki/PSMD1 | 26S proteasome non-ATPase regulatory subunit 1, also as known as 26S Proteasome Regulatory Subunit Rpn2 (systematic nomenclature), is a protein that in humans is encoded by the PSMD1 gene. This protein is one of the 19 essential subunits that contributes to the complete assembly of 19S proteasome complex.
Structure
Gene expression
The gene PSMD1 encodes the largest non-ATPase subunit of the 19S regulator base, which is responsible for substrate recognition and binding. The human PSMD1 gene has 25 exons and locates at chromosome band 2q37.1. The human protein 26S proteasome non-ATPase regulatory subunit 1 is 106 kDa in size and composed of 953 amino acids. The calculated theoretical pI of this protein is 5.25. An alternative splicing during gene expression generates an isoform of the protein in which the amino acid sequence from 797-827 is missing.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled prot |
https://en.wikipedia.org/wiki/PSMD2 | 26S proteasome non-ATPase regulatory subunit 2, also as known as 26S Proteasome Regulatory Subunit Rpn1 (systematic nomenclature), is an enzyme that in humans is encoded by the PSMD2 gene.
Structure
Gene expression
The gene PSMD2 encodes a non-ATPase subunit of the 19S regulator base, which is responsible for substrate recognition and binding. The gene PSMD2 encodes one of the non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. The human PSMD2 gene has 23 exons and locates at chromosome band 3q27.1. The human protein 26S proteasome non-ATPase regulatory subunit 2 is 100 kDa in size and composed of 909 amino acids. The calculated theoretical pI of this protein is 5.10. Two expression isoforms are generated by alternative splicing, in which either 1-130 or 1-163 of the amino acid sequence is missing.
Complex assembly
26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. |
https://en.wikipedia.org/wiki/PSMD11 | 26S proteasome non-ATPase regulatory subunit 11 is an enzyme that in humans is encoded by the PSMD11 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 |
https://en.wikipedia.org/wiki/RAD1%20homolog | Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.
Function
This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.
Meiosis
During meiosis, double-strand breaks occur in DNA that initiate recombination. Recombination is a process that repairs the breaks and also promotes faithful chromosome segregation. In yeast the 9-1-1 complex (including RAD1) facilitates meiotic recombination. An alternative, but inaccurate, mechanism for repairing double-strand breaks is non-homologous end joining. In the rice plant, the 9-1-1 complex promotes accurate meiotic recombination by suppressing the alternative process of non-homologous end joining.
During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes. Testis-specific disruption of RAD1 in mice results in defective double-strand break repair, depletion of germ cells and infertility.
Interactions
RAD1 homolog has been shown to interact with:
HUS1,
RAD17, and
RAD9A,
References
Further reading |
https://en.wikipedia.org/wiki/SNAI1 | Zinc finger protein SNAI1 (sometimes referred to as Snail) is a protein that in humans is encoded by the SNAI1 gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.
Function
The Drosophila embryonic protein SNAI1, commonly known as Snail, is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila Snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. SNAI1 zinc-fingers (ZF) binds to E-box, an E-cadherin promoter region, and represses the expression of the adhesion molecule, which induces the tightly bound epithelial cells to break loose from each other and migrate into the developing embryo to become mesenchymal cells. This process allows for the formation of the mesodermal layer in the developing embryo. Though SNAI1 is shown to repress expression of E-cadherin in epithelial cells, studies have shown homozygous mutant embryos are still able to form a mesodermal layer. However, the mesodermal layer present shows characteristics of epithelial cells and not mesenchymal cells (the mutant mesoderm cells exhibited a polarized state). Other studies show that mutation |
https://en.wikipedia.org/wiki/Protein%20inhibitor%20of%20activated%20STAT2 | E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.
Interactions
Protein inhibitor of activated STAT2 has been shown to interact with:
Androgen receptor,
DNMT3A,
PARK7, and
UBE2I.
References
Further reading |
https://en.wikipedia.org/wiki/AIFM1 | Apoptosis-inducing factor 1, mitochondrial is a protein that in humans is encoded by the AIFM1 gene on the X chromosome. This protein localizes to the mitochondria, as well as the nucleus, where it carries out nuclear fragmentation as part of caspase-independent apoptosis.
Structure
AIFM1 is expressed as a 613-residue precursor protein that containing a mitochondrial targeting sequence (MTS) at its N-terminal and two nuclear leading sequences (NLS). Once imported into the mitochondria, the first 54 residues of the N-terminal are cleaved to produce the mature protein, which inserts into the inner mitochondrial membrane. The mature protein incorporates the FAD cofactor and folds into three structural domains: the FAD-binding domain, the NAD-binding domain, and the C-terminal. While the C-terminal is responsible for the proapoptotic activity of AIFM1, the FAD-binding and NAD-binding domains share the classical Rossmann topology with other flavoproteins and the NAD(P)H dependent reductase activity.
Three alternative transcripts encoding different isoforms have been identified for this gene. Two alternatively spliced mRNA isoforms correspond to the inclusion/exclusion of the C-terminal and the reductase domains. A pseudogene that is thought to be related to this gene has been identified on chromosome 10.
Function
This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells that is found in the mitochondrial intermembrane space in healthy cells. Indu |
https://en.wikipedia.org/wiki/TANK-binding%20kinase%201 | TBK1 (TANK-binding kinase 1) is an enzyme with kinase activity. Specifically, it is a serine / threonine protein kinase. It is encoded by the TBK1 gene in humans. This kinase is mainly known for its role in innate immunity antiviral response. However, TBK1 also regulates cell proliferation, apoptosis, autophagy, and anti-tumor immunity. Insufficient regulation of TBK1 activity leads to autoimmune, neurodegenerative diseases or tumorigenesis.
Structure and regulation of activity
TBK1 is a non-canonical IKK kinase that phosphorylates the nuclear factor kB (NFkB). It shares sequence homology with canonical IKK.
The N-terminus of the protein contains the kinase domain (region 9-309) and the ubiquitin-like domain (region 310-385). The C-terminus is formed by two coiled-coil structures (region 407-713) that provide a surface for homodimerization.
The autophosphorylation of serine 172, which requires homodimerization and ubiquitinylation of lysines 30 and 401, is necessary for kinase activity.
Involvement in signaling pathways
TBK1 is involved in many signaling pathways and forms a node between them. For this reason, regulation of its involvement in individual signaling pathways is necessary. This is provided by adaptor proteins that interact with the dimerization domain of TBK1 to determine its location and access to substrates. Binding to TANK leads to localization to the perinuclear region and phosphorylation of substrates which is required for subsequent production of type |
https://en.wikipedia.org/wiki/Aprataxin | Aprataxin is a protein that in humans is encoded by the APTX gene.
This gene encodes a member of the histidine triad (HIT) superfamily, some of which have nucleotide-binding and diadenosine polyphosphate hydrolase activities. The encoded protein may play a role in single-stranded DNA repair. Mutations in this gene have been associated with ataxia–ocular apraxia. Multiple transcript variants encoding distinct isoforms have been identified for this gene, however, the full length nature of some variants has not been determined.
Function
Aprataxin removes AMP from DNA ends following abortive ligation attempts by DNA Ligase IV during non-homologous end joining, thereby permitting subsequent attempts at ligation.
DNA strand breaks
Ataxia oculomotor apraxia-1 is a neurological disorder caused by mutations in the APTX gene that encodes aprataxin. The neurological disorder appears to be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events.
Premature aging
Aptx−/− mutant mice have been generated, but they lack an obvious phenotype. Another mouse model was generated in which a mutation of superoxide dismutase I (SOD1) is expressed in an Aptx−/− mouse. The SOD1 mutation causes a reduction in transcription recovery following oxidative stress. These mice showed accelerated cellular senescence. This study also demonstrated a protective role of Aptx in vivo and suggested that the loss of Aptx function results in progressive |
https://en.wikipedia.org/wiki/HIST2H3C | Histone H3.2 is a protein that in humans is encoded by the HIST2H3C gene.
Function
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in a histone cluster on chromosome 1. This gene is one of four histone genes in the cluster that are duplicated; this record represents the telomeric copy.
Interactions
HIST2H3C has been shown to interact with NCOA6.
References
Further reading
External links |
https://en.wikipedia.org/wiki/Collagen%2C%20type%20X%2C%20alpha%201 | Collagen alpha-1(X) chain is a protein that in humans is a member of the collagen family encoded by the COL10A1 gene.
This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer. Type X collagen has a short triple helical collagen domain flanked by the N-terminal NC2 and the C-terminal NC1 domains. The C-terminal NC1 domain has complement C1q-like structure. Collagen X forms hexamer complexes through the association of NC1 regions. Mutations in this gene are associated with Schmid type metaphyseal chondrodysplasia (SMCD) and Japanese type spondylometaphyseal dysplasia (SMD).
DDR2 is a collagen receptor for it.
Recent studies into the early detection of colon cancer have identified COL10A1 protein levels in serum as a potential diagnostic biomarker candidate to detect both adenoma lesions and tumor.
Collagen alpha-1(X) undergoes degradation in the active growth plate releasing an intact NC1 region with a small amount of collagenous region attached. This degradation byproduct has been deemed CXM and has potential to be a useful biomarker to assess real time growth velocity in children and fracture healing in adults.
References
Further reading |
https://en.wikipedia.org/wiki/Crystallin%2C%20gamma%20D | Gamma-crystallin D is a protein that in humans is encoded by the CRYGD gene.
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation.
References
Further reading |
https://en.wikipedia.org/wiki/DAZ1 | Deleted in azoospermia 1, also known as DAZ1, is a protein which in humans is encoded by the DAZ1 gene.
Function
This gene is a member of the DAZ gene family and is a candidate for the human Y-chromosomal azoospermia factor (AZF). Its expression is restricted to pre-meiotic germ cells, particularly in spermatogonia. It encodes an RNA-binding protein that is important for spermatogenesis. Four copies of this gene are found on chromosome Y within palindromic duplications; one pair of genes is part of the P2 palindrome and the second pair is part of the P1 palindrome. Each gene contains a 2.4 kb repeat including a 72-bp exon, called the DAZ repeat; the number of DAZ repeats is variable and there are several variations in the sequence of the DAZ repeat. Each copy of the gene also contains a 10.8 kb region that may be amplified; this region includes five exons that encode an RNA recognition motif (RRM) domain. This gene contains three copies of the 10.8 kb repeat. However, no transcripts containing three copies of the RRM domain have been described; thus the RefSeq for this gene contains only two RRM domains.
Interactions
DAZ1 has been shown to interact with DAZAP2, DAZL and DAZ associated protein 1.
References
Further reading |
https://en.wikipedia.org/wiki/Dopachrome%20tautomerase | Dopachrome tautomerase (dopachrome delta-isomerase, tyrosine-related protein 2), also known as DCT, is a human gene. Its expression is regulated by the microphthalmia-associated transcription factor (MITF).
See also
Tyrosinase-related protein 1 (TYRP1)
Dopachrome, a cyclization product of L-DOPA and is an intermediate in the biosynthesis of melanin.
References
Further reading |
https://en.wikipedia.org/wiki/DDX5 | Probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 is an enzyme that in humans is encoded by the DDX5 gene.
Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an RNA-dependent ATPase, and also a proliferation-associated nuclear antigen, specifically reacting with the simian virus 40 tumor antigen. This gene consists of 13 exons, and alternatively spliced transcripts containing several intron sequences have been detected, but no isoforms encoded by these transcripts have been identified.
Interactions
DDX5 has been shown to interact with:
AKAP8,
DDX17 (p72),
DHX9 (RNA helicase A),
Estrogen receptor alpha,
Fibrillarin,
HDAC1,
Nuclear receptor coactivator 1,
Nuclear receptor coactivator 2,
Nuclear receptor coactivator 3,
p53,
CTCF.
References
Further reading
EC 3.6.4 |
https://en.wikipedia.org/wiki/DVL1 | Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.
Function
DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. DVL1 is a candidate gene for processes involved in cell transformations involved in neuroblastoma. The Schwartz-Jampel syndrome and Charcot-Marie-Tooth disease type 2A have been mapped to the same region as DVL1. The phenotypes of these diseases may be consistent with defects which might be expected from aberrant expression of a DVL gene during development. Three transcript variants encoding three different isoforms have been found for this gene.
Interactions
DVL1 has been shown to interact with:
AXIN1,
DVL3,
EPS8, and
Mothers against decapentaplegic homolog 3.
See also
Dishevelled
References
Further reading
External links
DVL1 on the Atlas of Genetics and Oncology |
https://en.wikipedia.org/wiki/GRIK2 | Glutamate ionotropic receptor kainate type subunit 2, also known as ionotropic glutamate receptor 6 or GluR6, is a protein that in humans is encoded by the GRIK2 (or GLUR6) gene.
Function
This gene encodes a subunit of a kainate glutamate receptor. This receptor may have a role in synaptic plasticity, learning, and memory. It also may be involved in the transmission of visual information from the retina to the hypothalamus. The structure and function of the encoded protein is influenced by RNA editing. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene.
Clinical significance
Homozygosity for a GRIK2 deletion-inversion mutation is associated with non-syndromic autosomal recessive mental retardation.
Interactions
GRIK2 has been shown to interact with:
DLG1,
DLG4,
GRID2,
GRIK5,
GRIP1,
PICK1 and
SDCBP.
RNA Editing
Pre-mRNA for several neurotransmitter receptors and ion channels are substrates for ADARs, including AMPA receptor subunits (GluR2, GluR3, GluR4) and kainate receptor subunits (GluR5, GluR6). Glutamate-gated ion channels are made up of four subunits per channel, with each subunit contributing to the pore loop structure. The pore loop structure is similar to that found in K+ channels (e.g. the human Kv1.1 channel, whose pre-mRNA is also subject to A to I RNA editing). The diversity of ionotropic glutamate receptor subunits, as well as RNA splicing, is determined by RNA editing events of the individ |
https://en.wikipedia.org/wiki/GTF2H4 | General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.
Interactions
GTF2H4 has been shown to interact with:
GTF2F1,
MED21,
POLR2A,
TATA binding protein,
Transcription Factor II B, and
XPB.
See also
Transcription Factor II H
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Laminin%2C%20beta%201 | Laminin subunit beta-1 is a protein that in humans is encoded by the LAMB1 gene.
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms, which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains, which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contai |
https://en.wikipedia.org/wiki/Myotubularin%201 | Myotubularin is a protein that in humans is encoded by the MTM1 gene.
This gene is a member of a gene family that encodes lipid phosphatases. Myotubularin is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on X-Linked Myotubular Myopathy or Centronuclear Myopathy
Human proteins |
https://en.wikipedia.org/wiki/NME2 | Nucleoside diphosphate kinase B is an enzyme that in humans is encoded by the NME2 gene.
Function
Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by this gene) isoforms. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene. Co-transcription of this gene and the neighboring upstream gene (NME1) generates naturally occurring transcripts (NME1-NME2) which encode a fusion protein consisting of sequence sharing identity with each individual gene product.
Interactions
NME2 has been shown to interact with NME3 and HERC5.
References
Further reading |
https://en.wikipedia.org/wiki/NT5E | 5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the NT5E gene. CD73 commonly serves to convert AMP to adenosine.
Transcription factor binding sites
NT5E contains binding sites for transcription factors AP-2, SMAD proteins, SP-1 and elements responsive to c-AMP , which can be found in c-AMP promoter parts. SMADs 2, 3, 4 and 5 and SP-1 are binding to the NT5E promoter in rats, as was proven in chromatin immunoprecipitation assays. Due to the fact, that the human and rat NT5E transcripts are 89% identical, human NT5E could be also regulated by SMAD proteins.
Function
Ecto-5-prime-nucleotidase (5-prime-ribonucleotide phosphohydrolase; EC 3.1.3.5) catalyzes the conversion at neutral pH of purine 5-prime mononucleotides to nucleosides, the preferred substrate being AMP. The enzyme consists of a dimer of 2 identical 70-kD subunits bound by a glycosyl phosphatidyl inositol linkage to the external face of the plasma membrane. The enzyme is used as a marker of lymphocyte differentiation. Consequently, a deficiency of NT5 occurs in a variety of immunodeficiency diseases (e.g., see MIM 102700, MIM 300300). Other forms of 5-prime nucleotidase exist in the cytoplasm and lysosomes and can be distinguished from ecto-NT5 by their substrate affinities, requirement for divalent magnesium ion, activation by ATP, and inhibition by inorganic phosphate. Rare allelic variants are associated with a synd |
https://en.wikipedia.org/wiki/PPP2R4 | Serine/threonine-protein phosphatase 2A regulatory subunit B is an enzyme that in humans is encoded by the PPP2R4 gene.
Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.
Interactions
PPP2R4 has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2.
References
Further reading |
https://en.wikipedia.org/wiki/PSMD8 | 26S proteasome non-ATPase regulatory subunit 8 is an enzyme that in humans is encoded by the PSMD8 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. A pseudogene has been identified on chromosome 1.
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 |
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