Adapter molecule crk

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.^[5]

CRK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JU5, 2DVJ, 2EYV, 2EYW, 2EYX, 2EYY, 2EYZ, 2MS4
Identifiers
Aliases	CRK, CRKII, p38, v-crk avian sarcoma virus CT10 oncogene homolog, CRK proto-oncogene, adaptor protein
External IDs	OMIM: 164762; MGI: 88508; HomoloGene: 81850; GeneCards: CRK; OMA:CRK - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.3 Start 1,420,689 bp[1] End 1,463,162 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B5|11 45.92 cM Start 75,570,085 bp[2] End 75,597,734 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte mucosa of sigmoid colon pericardium lower lobe of lung trigeminal ganglion Pons corpus epididymis body of tongue Achilles tendon seminal vesicula Top expressed in atrioventricular valve Gonadal ridge ureter seminal vesicula atrium epithelium of stomach decidua parotid gland lateral septal nucleus primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-macromolecule adaptor activity protein domain specific binding ephrin receptor binding protein binding enzyme binding insulin-like growth factor receptor binding cytoskeletal protein binding scaffold protein binding phosphotyrosine residue binding SH3 domain binding SH2 domain binding protein self-association protein phosphorylated amino acid binding protein tyrosine kinase binding Cellular component cytoplasm cytosol membrane plasma membrane actin cytoskeleton extracellular exosome nucleus membrane raft protein-containing complex Biological process Fc-gamma receptor signaling pathway involved in phagocytosis regulation of GTPase activity ephrin receptor signaling pathway regulation of transcription by RNA polymerase II regulation of Rac protein signal transduction vascular endothelial growth factor receptor signaling pathway regulation of actin cytoskeleton organization positive regulation of substrate adhesion-dependent cell spreading response to yeast positive regulation of smooth muscle cell migration response to hepatocyte growth factor response to hydrogen peroxide negative regulation of natural killer cell mediated cytotoxicity cellular response to transforming growth factor beta stimulus cellular response to nitric oxide response to peptide cellular response to nerve growth factor stimulus cellular response to insulin-like growth factor stimulus cellular response to endothelin regulation of cell shape regulation of signal transduction positive regulation of cell growth regulation of protein binding regulation of wound healing negative regulation of wound healing response to cholecystokinin regulation of cell motility negative regulation of cell motility neuron migration regulation of leukocyte migration lipid metabolism dendrite development cytokine-mediated signaling pathway hippocampus development cerebral cortex development establishment of cell polarity regulation of cell adhesion mediated by integrin helper T cell diapedesis reelin-mediated signaling pathway regulation of dendrite development cell chemotaxis activation of GTPase activity cerebellar neuron development regulation of T cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1398 12928 Ensembl ENSG00000167193 ENSMUSG00000017776 UniProt P46108 Q64010 RefSeq (mRNA) NM_016823 NM_005206 NM_001277219 NM_001277221 NM_133656 RefSeq (protein) NP_005197 NP_058431 NP_001264148 NP_001264150 NP_598417 Location (UCSC) Chr 17: 1.42 – 1.46 Mb Chr 11: 75.57 – 75.6 Mb PubMed search [3] [4]
Wikidata
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The CRK protein participates in the Reelin signaling cascade downstream of DAB1.^[6][7]

Function

Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. This protein has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.^[8]

Crk together with CrkL participates in the Reelin signaling cascade downstream of DAB1.^[6][7]

v-Crk, a transforming oncoprotein from avian sarcoma viruses, is a fusion of viral "gag" protein with the SH2 and SH3 domains of cellular Crk.^[9] The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase domains, but capable of stimulating phosphorylation of tyrosines in cells.^[10]

Crk should not be confused with Src, which also has cellular (c-Src) and viral (v-Src) forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase.

Interactions

CRK (gene) has been shown to interact with:

• BCAR1,^{[11][12][13][14][15][16][17][18][19][excessive citations]}
• Cbl gene,^[20][21]
• Dock180,^{[22][13][14][23][24]}
• EPS15,^[25]
• Epidermal growth factor receptor,^[26][27]
• Grb2,^[28][22][29]
• IRS4,^[30][31]
• MAP4K1,^[32][33][34]
• MAPK8,^[35]
• NEDD9,^[36][37]
• PDGFRA,^[38][39]
• PDGFRB,^[38]
• PTK2,^[13][16]
• Paxillin^[16][40]
• RAPGEF1,^[41]
• RICS,^[42][43]
• SH3KBP1,^[44] and
• SOS1.^[29]

See also

• CrkL, "Crk-like" protein