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The tetraspanin family is a group of cell surface proteins that regulate cell development, activation, growth and motility. Each member contains four hydrophobic domains and participates in the mediation of signal transduction. NET-5, also known as TSPAN9 (tetraspanin 9), is a 239 amino acid multi-pass membrane protein that belongs to the tetraspanin (TM4SF) family. NET-5 forms a complex with GPVI in the tetraspanin microdomains on the platelet surface, and is encoded by a gene that maps to human chromosome 12p13.33. Chromosome 12 encodes over 1,100 genes and comprises approximately 4.5% of the human genome. Chromosome 12 is associated with a variety of diseases and afflictions, including hypochondrogenesis, achondrogenesis, Kniest dysplasia, Noonan syndrome and trisomy 12p, which causes facial developmental defects and seizure disorders.

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Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.

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PLEKHM3 (pleckstrin homology domain containing, family M, member 3), also known as DAPR or PLEKHM1L (pleckstrin homology domain containing, family M, member 1-like), is a 761 amino acid phosphoprotein that contains two pleckstrin homology (PH) domains and one phorbol-ester/DAG-type zinc finger. Conserved in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish, PLEKHM3 exists as three alternatively spliced isoforms that participate in metal ion binding. The gene that encodes PLEKHM3 maps to human chromosome 2q33.3. As the second largest human chromosome, chromosome 2 makes up approximately 8% of the human genome and contains 237 million bases encoding over 1,400 genes. Chromosome 2 contains a probable vestigial second centromere, as well as vestigial telomeres, which gives credence to the hypothesis that human chromosome 2 formed as a result of an ancient fusion of two ancestral chromosomes, which are still present in modern day apes.

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C/EBP is a DNA-binding protein that recognizes two different motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers.

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The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein shares a similar domain structure with CARD11 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. Two alternatively spliced variants of this gene encoding distinct isoforms have been reported.

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Acts as a transcriptional activator or repressor. Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T-cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression. Together with PAX6, transactivates strongly the glucagon gene promoter through the G1 element. Activates transcription of the CD13 proximal promoter in endothelial cells. Represses transcription of the CD13 promoter in early stages of myelopoiesis by affecting the ETS1 and MYB cooperative interaction. Involved in the initial chondrocyte terminal differentiation and the disappearance of hypertrophic chondrocytes during endochondral bone development. Binds to the sequence 5'-[GT]G[GC]N[GT]NCTCAGNN-3' in the L7 promoter. Binds to the T-MARE (Maf response element) sites of lens-specific alpha- and beta-crystallin gene promoters. Binds element G1 on the glucagon promoter. Binds an AT-rich region adjacent to the TGC motif (atypical Maf response element) in the CD13 proximal promoter in endothelial cells (By similarity). When overexpressed, represses anti-oxidant response element (ARE)-mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters.

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G protein-coupled receptors (GPCRs) represent a large superfamily of cell-surface receptors that are involved in a multitude of physiological processes such as perception of sensory information, modulation of synaptic transmission, hormone release/actions, regulation of cell contraction/migration and cell growth/differentiation. GPCRs interact with G proteins (heterotrimeric GTPases) to synthesize intracellular second messengers, such as diacylglycerol, cyclic AMP, inositol phosphates and calcium ions. Their diverse biological functions range from vision and olfaction to neuronal and endocrine signaling and are involved in many pathological conditions. GRIN2 (G protein-regulated inducer of neurite outgrowth 2), also known as GPRIN2, is a 458 amino acid protein that is expressed in cerebellum and is thought to play a role in neurite outgrowth. GRIN2 interacts with activated G?oand G?, and is encoded by a gene that maps to human chromosome 10q11.22.

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Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.

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Nox4 is a renal gp91-phox homolog highly expressed at the site of erythropoietin production in the proximal convoluted tubule epithelial cells of the renal cortex. Nox4 is also expressed in fetal tissues, placenta, glioblastoma and vascular cells. Like gp91-phox, the enzymatic activity of Nox4 produces superoxide anions. In vascular cells, the addition of angiotensin II increases Nox4 expression, which suggests a role for Nox-4 in vascular oxidative stress response.

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Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues.

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Hsp22 (HSPB8) is a 196-amino acid protein that contains a central portion homologous to a highly conserved HSP-alpha crystallin domain common to all the small heat shock protein (HSP20) family members. Hsp22 is a monomeric protein which interacts with HSPB1. It displays temperature-dependent chaperone activity. The highest abundance of Hsp22 is in skeletal muscle, heart, and placenta. Mutations in the HSPB8 gene are associated with the inherited peripheral neuropathies, autosomal dominant distal hereditary motor neuropathy type IIA (dSMA) and axonal Charcot-Marie-Tooth disease type 2L (CMT2L).

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Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.

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Plays an important role in the degradation of dermatan and keratan sulfates.

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WASP (for Wiskott-Aldrich syndrome protein) and N-WASP are downstream effectors of Cdc42 that are implicated in Actin polymerization and cytoskeletal organization. The WASP family also includes VASP (vasodilator-stimulated phosphoprotein) and Mena (for mammalian enabled protein), which accumulate at focal adhesions and are also involved in the regulation of the Actin cytoskeleton. The WAVE proteins are related to the WASP family proteins and are likewise involved in mediating Actin reorganization downstream of the Rho family of small GTPases. The protein homologs WAVE1 and WAVE2 regulate membrane ruffling by inducing the formation of Actin filament clusters in response to GTP binding and by activating Rac. They mediate Actin polymerization by cooperating with the Arp2/3 complex, thereby promoting the formation of Actin filaments. WAVE1, which is also designated SCAR (suppressor of cAR), is expressed primarily in the brain, while WAVE2 is widely expressed, with the expression highest in peripheral blood leukocytes. WAVE3 forms a multiprotein complex that links receptor kinases with Actin and plays a role in the transduction of signals involving changes in cell shape, function or motility.

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Importin 7 is a 1,038 amino acid protein encoded by the human gene IPO7. Importin-7 belongs to the importin b family and contains one importin N-terminal domain. Importin-7 functions in nuclear protein import, either by acting as an autonomous nuclear transport receptor or as an adapter-like protein in association with the Importin b subunit KPNB1. Acting autonomously, Importin-7 is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to Importin-7, the Importin-7/substrate complex dissociates and Importin-7 is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. Importin-7 is a nuclear protein that is expressed in most tissues.

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The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein. This gene is located adjacent to the ocular albinism gene and it is thought to be involved in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype. Four transcript variants encoding two different isoforms have been found for this gene. This gene is highly similar to the Y chromosome TBL1Y gene. [provided by RefSeq].