SH2D3C
SH2 domain containing 3C, also known as SH2D3C, is a protein that in humans is encoded by the SH2D3C gene.[3]
Function
Sh2d3c is a gene on human chromosome 9 that encodes an SH2 domain containing protein known as NSP3. The mouse homologue is found on chromosome 2. The NSP (Novel SH2-containing Protein) family of proteins contains three members, NSP1, NSP2, and NSP3 (this protein), all of which have a similar architecture, with an N-terminal SH2 domain, a proline serine rich region, which contains consensus sequences for MAP kinase substrates, and a conserved C-terminus, which binds to the Cas family of adapter proteins, and also shows homology to GEF domains.
NSP3 was originally identified by three independent groups of researchers.[4][5][6] The mouse homologue of NSP3 has been shown to have two distinct isoforms, generated by alternative splicing, that are expressed in different tissues. The shorter isoform, known as Chat (Cas/Hef1 associated signal transducer) is expressed in brain, lung, heart, kidney, muscle, liver, and intestine, while the larger isoform, known as Chat-H (the "H" is for Hematopoietic), is expressed in spleen, thymus, and lymph nodes.[6] The two isoforms differ only in their N-terminus, which has been shown by one group to be important for membrane localization.[7]
Through its interaction with Hef1, Chat-H, has been shown to be an important regulator of lymphocyte adhesion, acting upstream of Rap1 in the integrin activation pathway.[7]
References
Further reading
- Near RI, Zhang Y, Makkinje A, et al. (2007). "AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology". J. Cell. Physiol. 212 (3): 655–65. doi:10.1002/jcp.21059. PMC 2640322
. PMID 17427198.
- Vervoort VS; Roselli S; Oshima RG; Pasquale EB (2007). "Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling". Gene. 391 (1–2): 161–70. doi:10.1016/j.gene.2006.12.016. PMC 1876674. PMID 17270363.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Dail M, Kalo MS, Seddon JA, et al. (2004). "SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases". J. Biol. Chem. 279 (40): 41892–902. doi:10.1074/jbc.M402929200. PMID 15272013.
- Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9". Nature. 429 (6990): 369–74. doi:10.1038/nature02465. PMC 2734081. PMID 15164053.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
- Sakakibara A; Hattori S; Nakamura S; Katagiri T (2003). "A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells". J. Biol. Chem. 278 (8): 6012–7. doi:10.1074/jbc.M207942200. PMID 12486027.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Sakakibara A; Hattori S (2000). "Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways". J. Biol. Chem. 275 (9): 6404–10. doi:10.1074/jbc.275.9.6404. PMID 10692442.
- Dodelet VC, Pazzagli C, Zisch AH, et al. (1999). "A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A". J. Biol. Chem. 274 (45): 31941–6. doi:10.1074/jbc.274.45.31941. PMID 10542222.
- Lu Y; Brush J; Stewart TA (1999). "NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway". J. Biol. Chem. 274 (15): 10047–52. doi:10.1074/jbc.274.15.10047. PMID 10187783.
- Regelmann AG; Danzl NM; Wanjalla C; Alexandropoulos K (2006). "The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking". Immunity. 25 (6): 907–18. doi:10.1016/j.immuni.2006.09.014. PMID 17174122.
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