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Available structures
PDB Ortholog search: PDBe RCSB
Aliases SH2D3C, Sh2d3c, Chat, Nsp3, Shep1, PRO34088, SH2 domain containing 3C
External IDs MGI: 1351631 HomoloGene: 69145 GeneCards: SH2D3C
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 9: 127.74 – 127.78 Mb Chr 2: 32.72 – 32.76 Mb
PubMed search [1] [2]
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SH2 domain containing 3C, also known as SH2D3C, is a protein that in humans is encoded by the SH2D3C gene.[3]


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]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ "Entrez Gene: SH2D3C SH2 domain containing 3C". 
  4. ^ Lu Y, Brush J, Stewart TA (April 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". The Journal of Biological Chemistry. 274 (15): 10047–52. doi:10.1074/jbc.274.15.10047. PMID 10187783. 
  5. ^ Dodelet VC, Pazzagli C, Zisch AH, Hauser CA, Pasquale EB (November 1999). "A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A". The Journal of Biological Chemistry. 274 (45): 31941–6. doi:10.1074/jbc.274.45.31941. PMID 10542222. 
  6. ^ a b Sakakibara A, Hattori S (March 2000). "Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways". The Journal of Biological Chemistry. 275 (9): 6404–10. doi:10.1074/jbc.275.9.6404. PMID 10692442. 
  7. ^ a b Regelmann AG, Danzl NM, Wanjalla C, Alexandropoulos K (December 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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