Reviewed, UniProtKB/Swiss-Prot Q64010 (CRK_MOUSE)

Names and origin

Protein names

Recommended name:
    Proto-oncogene C-crk
Alternative name(s):
    p38
    Adapter molecule crk

Gene names

Name:	Crk
Synonyms:	Crko

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	304 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with ABL1, C3G, SOS, MAP4K1 and MAPK8 via its first SH3 domain. Interacts with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 via its SH2 domain upon stimulus-induced tyrosine phosphorylation. Interacts with several tyrosine-phosphorylated growth factor receptors such as EGFR, PDGFR and INSR via its SH2 domain. Interacts with DOCK1, DOCK4, C3G and EPS15 via its SH3 domain. Interacts with SHB By similarity. Interacts with DOCK3. Interacts with REPS1 and DDEF1/ASAP1 via its SH3 domain.
Subcellular location	CytoplasmBy similarity. Cell membraneBy 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 SHB.
Post-translational modification	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.
Sequence similarities	Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein phosphorylated amino acid binding Inferred from direct assay. Source: MGI
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 304

304

Proto-oncogene C-crk

PRO_0000079352

Regions

Domain

13 – 118

106

SH2

Domain

132 – 192

61

SH3 1

Domain

256 – 296

41

SH3 2

Amino acid modifications

Modified residue

41

1

Phosphoserine

Modified residue

42

1

Phosphothreonine

Modified residue

74

1

Phosphoserine By similarity

Modified residue

83

1

Phosphoserine By similarity

Modified residue

221

1

Phosphotyrosine

Modified residue

239

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

205 – 304

100

Missing in isoform Crk-I.

VSP_004174

Secondary structure

1

.

.

.

.

.

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304

Helix Strand Turn

Details...

Beta strand

136 – 141

6

Beta strand

158 – 163

6

Beta strand

165 – 173

9

Beta strand

179 – 183

5

Helix

184 – 186

3

Beta strand

238 – 244

7

Beta strand

252 – 254

3

Beta strand

262 – 268

7

Beta strand

271 – 273

3

Beta strand

275 – 279

5

Beta strand

282 – 286

5

Helix

288 – 290

3

Beta strand

291 – 294

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Crk-II [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 5491896FC7A89065	FASTA	304	33,815
	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
	Isoform Crk-I [UniParc]. Checksum: 35B7AC1188657461		204	22,847
	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 MIPVPYVEKY RPASASVSAL IGGN

References

	« Hide 'large scale' referencesShow '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: 8183562] [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. , 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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRK-II). Strain: C57BL/6J. Tissue: Skin.
[3]	"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: 9395447] [Abstract] Cited for: INTERACTION WITH REPS1. Tissue: Muscle.
[4]	"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: 9819391] [Abstract] Cited for: INTERACTION WITH DDEF1/ASAP1.
[5]	"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: 10854253] [Abstract] Cited for: INTERACTION WITH DOCK3. Tissue: Brain.
[6]	"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: 12842890] [Abstract] Cited for: INTERACTION WITH CBLB.
[7]	"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: 8194526] [Abstract] Cited for: PHOSPHORYLATION AT TYR-221, INTERACTION WITH ABL1.
[8]	"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: 15345747] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-221, MASS SPECTROMETRY. Tissue: Brain.
[10]	"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: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42, MASS SPECTROMETRY. Tissue: Liver.
[11]	"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: 7735837] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 134-190.
[12]	"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: 9851931] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 133-191.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

S72408 mRNA. Translation: AAB30755.1.
AK028488 mRNA. Translation: BAC25976.1.

RefSeq

NP_598417.2.

UniGene

Mm.280125

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B07	X-ray	2.50	A	134-190	[»]
1CKA	X-ray	1.50	A	134-190	[»]
1CKB	X-ray	1.90	A	134-190	[»]
1JU5	NMR	-	B	217-229	[»]
1M30	NMR	-	A	134-190	[»]
1M3A	NMR	-	A	136-190	[»]
1M3B	NMR	-	A	136-190	[»]
1M3C	NMR	-	A	134-190	[»]
2GGR	NMR	-	A	230-304	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q64010.

Genome annotation databases

Ensembl

ENSMUSG00000017776. Mus musculus. [Contig view]

GeneID

12928.

KEGG

mmu:12928.

Organism-specific databases

MGI

MGI:88508. Crk.

Phylogenomic databases

HOGENOM

Q64010.

HOVERGEN

Q64010.

Gene expression databases

ArrayExpress

Q64010.

CleanEx

MM_CRK.

GermOnline

ENSMUSG00000017776. Mus musculus.

Family and domain databases

InterPro

IPR000980. SH2.
IPR001452. SH3.
IPR011511. SH3_2.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

ProDom

PD000093. SH2. 1 hit.
PD000066. SH3. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

Q64010.

NextBio

282592.

SOURCE

Search...

Entry information

Entry name

CRK_MOUSE

Accession

Primary (citable) accession number: Q64010

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)