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Q64010 (CRK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adapter molecule crk
Alternative name(s):
Proto-oncogene c-Crk
p38
Gene names
Name:Crk
Synonyms:Crko
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length304 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Subunit structure

Interacts with ABL1, C3G, DOCK3, MAP4K1, MAPK8 and SOS 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). 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. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with CBLC. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity. Note: Translocated to the plasma membrane upon cell adhesion By similarity.

Tissue specificity

Ubiquitous.

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.

Post-translational modification

Isoform Crk-II is phosphorylated by KIT. 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.3 Ref.9

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IGF1RP080693EBI-2906540,EBI-475981From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Crk-II (identifier: Q64010-1)

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: Q64010-2)

The sequence of this isoform differs from the canonical sequence as follows:
     205-304: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 304303Adapter molecule crk
PRO_0000079352

Regions

Domain13 – 118106SH2
Domain132 – 19261SH3 1
Domain237 – 29660SH3 2

Sites

Site2371Proline switch By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue411Phosphoserine By similarity
Modified residue741Phosphoserine By similarity
Modified residue831Phosphoserine By similarity
Modified residue2211Phosphotyrosine; by ABL1 Ref.3
Modified residue2391Phosphotyrosine By similarity

Natural variations

Alternative sequence205 – 304100Missing in isoform Crk-I.
VSP_004174

Secondary structure

............................ 304
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Crk-II [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 5491896FC7A89065

FASTA30433,815
        10         20         30         40         50         60 
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY 

        70         80         90        100        110        120 
IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVAR 

       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 VRLLDQQNPD 


EDFS 

« Hide

Isoform Crk-I [UniParc].

Checksum: 35B7AC1188657461
Show »

FASTA20422,847

References

« Hide 'large scale' references
[1]"The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells."
Ogawa S., Toyoshima H., Kozutsumi H., Hagiwara K., Sakai R., Tanaka T., Hirano N., Mano H., Yazaki Y., Hirai H.
Oncogene 9:1669-1678(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CRK-I AND CRK-II).
Tissue: Liver.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRK-II).
Strain: C57BL/6J.
Tissue: Skin.
[3]"c-Abl kinase regulates the protein binding activity of c-Crk."
Feller S.M., Knudsen B., Hanafusa H.
EMBO J. 13:2341-2351(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-221, INTERACTION WITH ABL1.
[4]"An eps homology (EH) domain protein that binds to the ral-GTPase target, RalBP1."
Yamaguchi A., Urano T., Goi T., Feig L.A.
J. Biol. Chem. 272:31230-31234(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH REPS1.
Tissue: Muscle.
[5]"Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules."
Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.
J. Biol. Chem. 273:23410-23418(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLT1.
[6]"ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src."
Brown M.T., Andrade J., Radhakrishna H., Donaldson J.G., Cooper J.A., Randazzo P.A.
Mol. Cell. Biol. 18:7038-7051(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDEF1/ASAP1.
[7]"Isolation and characterization of novel presenilin binding protein."
Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R., Schubert D., Kimura H.
J. Neurochem. 75:109-116(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DOCK3.
Tissue: Brain.
[8]"Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling."
Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., Boyd A.W., Alewood P.F., Lackmann M.
J. Cell Sci. 115:1059-1072(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPHA3.
[9]"Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk."
Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.
Exp. Cell Res. 288:110-118(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIT, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION.
[10]"The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport."
Liu J., DeYoung S.M., Hwang J.B., O'Leary E.E., Saltiel A.R.
J. Biol. Chem. 278:36754-36762(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBLB.
[11]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[12]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[13]"Structural basis for the specific interaction of lysine-containing proline-rich peptides with the N-terminal SH3 domain of c-Crk."
Wu X., Knudsen B., Feller S.M., Zheng J., Sali A., Cowburn D., Hanafusa H., Kuriyan J.
Structure 3:215-226(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 134-190.
[14]"Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors."
Nguyen J.T., Turck C.W., Cohen F.E., Zuckermann R.N., Lim W.A.
Science 282:2088-2092(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 133-191.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S72408 mRNA. Translation: AAB30755.1.
AK028488 mRNA. Translation: BAC25976.1.
CCDSCCDS25055.1. [Q64010-1]
RefSeqNP_598417.2. NM_133656.5. [Q64010-1]
UniGeneMm.280125.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1B07X-ray2.50A134-190[»]
1CKAX-ray1.50A134-190[»]
1CKBX-ray1.90A134-190[»]
1JU5NMR-B217-228[»]
1M30NMR-A134-191[»]
1M3ANMR-A135-191[»]
1M3BNMR-A134-191[»]
1M3CNMR-A132-191[»]
2GGRNMR-A230-304[»]
ProteinModelPortalQ64010.
SMRQ64010. Positions 1-304.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198887. 25 interactions.
DIPDIP-57059N.
IntActQ64010. 22 interactions.
MINTMINT-4599411.

PTM databases

PhosphoSiteQ64010.

Proteomic databases

MaxQBQ64010.
PaxDbQ64010.
PRIDEQ64010.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000017920; ENSMUSP00000017920; ENSMUSG00000017776. [Q64010-1]
GeneID12928.
KEGGmmu:12928.
UCSCuc007keq.1. mouse. [Q64010-1]

Organism-specific databases

CTD1398.
MGIMGI:88508. Crk.

Phylogenomic databases

eggNOGNOG292767.
GeneTreeENSGT00390000001475.
HOGENOMHOG000236288.
HOVERGENHBG105616.
InParanoidQ64010.
KOK04438.
OMAVIYERRF.
OrthoDBEOG7NW69P.
PhylomeDBQ64010.
TreeFamTF321436.

Gene expression databases

ArrayExpressQ64010.
BgeeQ64010.
CleanExMM_CRK.
GenevestigatorQ64010.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 3 hits.
SSF55550. SSF55550. 2 hits.
PROSITEPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ64010.
NextBio282592.
PROQ64010.
SOURCESearch...

Entry information

Entry nameCRK_MOUSE
AccessionPrimary (citable) accession number: Q64010
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot