SH2D3C

SH2 domain containing 3C
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3T6G​
Identifiers
Symbols	SH2D3C ; CHAT; NSP3; PRO34088; SHEP1
External IDs	OMIM: 604722 MGI: 1351631 HomoloGene: 69145 GeneCards: SH2D3C Gene
Gene ontology Molecular function • SH3/SH2 adaptor activity • guanyl-nucleotide exchange factor activity • protein binding Cellular component • cytoplasm • membrane Biological process • JNK cascade • small GTPase mediated signal transduction • positive regulation of signal transduction • positive regulation of GTPase activity Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10044	27387
Ensembl	ENSG00000095370	ENSMUSG00000059013
UniProt	Q8N5H7	Q9QZS8
RefSeq (mRNA)	NM_001142531	NM_001252547
RefSeq (protein)	NP_001136003	NP_001239476
Location (UCSC)	Chr 9: 127.74 – 127.78 Mb	Chr 2: 32.72 – 32.76 Mb
PubMed search

SH2 domain containing 3C, also known as SH2D3C, is a protein that in humans is encoded by the SH2D3C gene.^[1]

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.^[2][3][4] 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.^[4] The two isoforms differ only in their N-terminus, which has been shown by one group to be important for membrane localization.^[5]

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.^[5]

References

1. "Entrez Gene: SH2D3C SH2 domain containing 3C".
2. 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.
3. 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.
4. Sakakibara A, Hattori S (1999). "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.
5. 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.

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.

External links

• SH2D3C human gene location in the UCSC Genome Browser.
• SH2D3C human gene details in the UCSC Genome Browser.