Q63768 (CRK_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Adapter molecule crk
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||304 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling By similarity.
Interacts with ABL1, C3G, SOS, MAP4K1, MAPK8 and DOCK3 via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine-phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated) By similarity. Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent. Interacts with EPHA3 (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated). Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1 By similarity. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1 By similarity.
CRK-II is expressed in all tissues and cells whereas CRK-I is expressed at lower level and in limited cell-types.
The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation By similarity.
The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB By similarity.
Isoform Crk-II is phosphorylated by KIT By similarity. Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway. Ref.2
Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form By similarity.
Belongs to the CRK family.
Contains 1 SH2 domain.
Contains 2 SH3 domains.
|Cellular component||Cell membrane|
|Coding sequence diversity||Alternative splicing|
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||activation of JUN kinase activityephrin receptor signaling pathway|
Inferred from sequence or structural similarity. Source: UniProtKBregulation of Rac protein signal transductionregulation of Rho GTPase activity
Inferred from sequence or structural similarity. Source: UniProtKBregulation of actin cytoskeleton organization
Inferred from sequence or structural similarity. Source: UniProtKBregulation of cellular component movement
Traceable author statement. Source: Reactomeplasma membrane
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Molecular_function||protein binding, bridging|
|Complete GO annotation...|
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform Crk-II (identifier: Q63768-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform Crk-I (identifier: Q63768-2) |
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 304||304||Adapter molecule crk||PRO_0000079353|
|Domain||13 – 118||106||SH2|
|Domain||132 – 192||61||SH3 1|
|Domain||237 – 296||60||SH3 2|
|Site||237||1||Proline switch By similarity|
Amino acid modifications
|Modified residue||41||1||Phosphoserine By similarity|
|Modified residue||42||1||Phosphothreonine By similarity|
|Modified residue||74||1||Phosphoserine By similarity|
|Modified residue||83||1||Phosphoserine By similarity|
|Modified residue||221||1||Phosphotyrosine; by ABL1 Ref.2|
|Modified residue||239||1||Phosphotyrosine By similarity|
|Alternative sequence||205 – 304||100||Missing in isoform Crk-I.||VSP_004175|
|Natural variant||244||1||Q → R in NRK-23 inactive mutant. |
|Natural variant||253||1||K → E in NRK-23 inactive mutant. |
|Mutagenesis||221||1||Y → F: No activation of Rac signaling. Ref.2|
|||"CrkII signals from epidermal growth factor receptor to Ras."|
Kizaka-Kondoh S., Matsuda M., Okayama H.
Proc. Natl. Acad. Sci. U.S.A. 93:12177-12182(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling."|
Abassi Y.A., Vuori K.
EMBO J. 21:4571-4582(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-221, MUTAGENESIS OF TYR-221.
|+||Additional computationally mapped references.|
|D44481 mRNA. Translation: BAA07924.1.|
|RefSeq||NP_062175.1. NM_019302.1. |
3D structure databases
|SMR||Q63768. Positions 1-304. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000006407; ENSRNOP00000006407; ENSRNOG00000025792. |
|RGD||2405. Crk. |
Enzyme and pathway databases
|Reactome||REACT_111984. Signal Transduction. |
Gene expression databases
|GermOnline||ENSRNOG00000025792. Rattus norvegicus. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR000980. SH2. |
|Pfam||PF00017. SH2. 1 hit. |
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 2 hits.
|SUPFAM||SSF50044. SH3. 2 hits. |
|PROSITE||PS50001. SH2. 1 hit. |
PS50002. SH3. 1 hit.
|Accession||Primary (citable) accession number: Q63768|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families