CRK, N-terminal SH3 domain (IPR035457)

Short name: CRK_SH3_N

Overlapping homologous superfamilies

Domain relationships

  • SH3 domain (IPR001452)
    • CRK, N-terminal SH3 domain (IPR035457)


This entry represents the N-terminal SH3 domain found in the CRK family members [PMID: 7735837].

CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers [PMID: 16472145, PMID: 11607838].

The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL [PMID: 7735837]. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). CrkI lacks the regulatory phosphorylation site and C-terminal SH3 domain present in CrkII and CrkL [PMID: 17515907, PMID: 19861495]. The N-terminal SH3 domain of CRKII has been shown to bind the recognizes proline-rich motifs (PRMs) found in cABL kinase; this interaction is involved in the regulation of cell spreading, microbial pathogenesis, and cancer metastasis [PMID: 27332121].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.