Q63768 (CRK_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adapter molecule crk

Alternative name(s):
Proto-oncogene c-Crk
p38

Gene names

Name:	Crk
Synonyms:	Crko

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	304 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	Cytoplasm. Cell membrane. Note: Translocated to the plasma membrane upon cell adhesion.
Tissue specificity	CRK-II is expressed in all tissues and cells whereas CRK-I is expressed at lower level and in limited cell-types.
Domain	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.
Post-translational modification	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.
Sequence similarities	Belongs to the CRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of JUN kinase activity Traceable author statement Ref.2. Source: RGD ephrin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of Rac protein signal transduction Inferred from mutant phenotype Ref.2. Source: RGD regulation of Rho GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of actin cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB regulation of cellular component movement Traceable author statement Ref.2. Source: RGD
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein binding, bridging Inferred from mutant phenotype Ref.1. Source: RGD
Complete GO annotation...

Alternative products

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:
     205-304: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 304	304	Adapter molecule crk		PRO_0000079353
Regions
	Domain	13 – 118	106	SH2
	Domain	132 – 192	61	SH3 1
	Domain	237 – 296	60	SH3 2
Sites
	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
Natural variations
	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.
Experimental info
	Mutagenesis	221	1	Y → F: No activation of Rac signaling. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Crk-II [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4CFBFB65BE72E265	FASTA	304	33,845
	10 20 30 40 50 60 MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY 70 80 90 100 110 120 IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR 130 140 150 160 170 180 SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG 190 200 210 220 230 240 MIPVPYVEKY RPASASVSAL IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA 250 260 270 280 290 300 RVIQKRVPNA YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPE EDFS
	Isoform Crk-I [UniParc]. Checksum: A485BF23887B6B80	FASTA	204	22,863
	10 20 30 40 50 60 MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY 70 80 90 100 110 120 IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR 130 140 150 160 170 180 SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG 190 200 MIPVPYVEKY RPASASVSAL IGGN

References

[1]	"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]. Tissue: Kidney.
[2]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D44481 mRNA. Translation: BAA07924.1.
IPI	IPI00208672. IPI00211893.
RefSeq	NP_062175.1. NM_019302.1.
UniGene	Rn.96136.
3D structure databases
ProteinModelPortal	Q63768.
SMR	Q63768. Positions 1-304.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-346964.
STRING	10116.ENSRNOP00000006407.
PTM databases
PhosphoSite	Q63768.
Proteomic databases
PaxDb	Q63768.
PRIDE	Q63768.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000006407; ENSRNOP00000006407; ENSRNOG00000025792.
GeneID	54245.
KEGG	rno:54245.
Organism-specific databases
CTD	1398.
RGD	2405. Crk.
Phylogenomic databases
eggNOG	NOG292767.
GeneTree	ENSGT00390000001475.
HOGENOM	HOG000236288.
HOVERGEN	HBG105616.
InParanoid	Q63768.
KO	K04438.
OrthoDB	EOG4WWRK5.
Enzyme and pathway databases
Reactome	REACT_111984. Signal Transduction.
Gene expression databases
ArrayExpress	Q63768.
Genevestigator	Q63768.
GermOnline	ENSRNOG00000025792. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR000980. SH2. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
Pfam	PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. PF07653. SH3_2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 2 hits. [Graphical view]
SUPFAM	SSF50044. SH3. 2 hits.
PROSITE	PS50001. SH2. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	610726.

Entry information

Entry name

CRK_RAT

Accession

Primary (citable) accession number: Q63768

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program