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Protein

Adapter molecule crk

Gene

CRK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Isoform Crk-II: Regulates cell adhesion, spreading and migration. 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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei237Proline switchBy similarity1

GO - Molecular functioni

  • cytoskeletal protein binding Source: Ensembl
  • ephrin receptor binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: Ensembl
  • phosphotyrosine residue binding Source: CAFA
  • protein phosphorylated amino acid binding Source: CAFA
  • protein self-association Source: CAFA
  • protein tyrosine kinase binding Source: CAFA
  • scaffold protein binding Source: Ensembl
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: CAFA
  • SH3 domain binding Source: CAFA

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-170984 ARMS-mediated activation
R-HSA-186763 Downstream signal transduction
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8875555 MET activates RAP1 and RAC1
R-HSA-8875656 MET receptor recycling
R-HSA-912631 Regulation of signaling by CBL
SignaLinkiP46108
SIGNORiP46108

Protein family/group databases

MoonDBiP46108 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Adapter molecule crk
Alternative name(s):
Proto-oncogene c-Crk
p38
Gene namesi
Name:CRK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000167193.7
HGNCiHGNC:2362 CRK
MIMi164762 gene
neXtProtiNX_P46108

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi150D → K: Abolishes interaction with DOCK1. 1 Publication1
Mutagenesisi169W → L: Abolishes interaction with DOCK5. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi1398
OpenTargetsiENSG00000167193
PharmGKBiPA26880

Chemistry databases

ChEMBLiCHEMBL5005

Polymorphism and mutation databases

BioMutaiCRK
DMDMi158939322

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000793512 – 304Adapter molecule crkAdd BLAST303

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei40PhosphoserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei74PhosphoserineCombined sources1
Modified residuei83PhosphoserineCombined sources1
Modified residuei108PhosphotyrosineCombined sources1
Modified residuei125PhosphoserineCombined sources1
Modified residuei221Phosphotyrosine; by ABL11 Publication1
Modified residuei239PhosphotyrosineCombined sources1
Isoform Crk-I (identifier: P46108-2)
Modified residuei194PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. 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.1 Publication
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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP46108
MaxQBiP46108
PaxDbiP46108
PeptideAtlasiP46108
PRIDEiP46108
ProteomicsDBi55732
55733 [P46108-2]
TopDownProteomicsiP46108-1 [P46108-1]
P46108-2 [P46108-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00399054
SWISS-2DPAGEiP46108

PTM databases

iPTMnetiP46108
PhosphoSitePlusiP46108

Expressioni

Gene expression databases

BgeeiENSG00000167193
CleanExiHS_CRK
ExpressionAtlasiP46108 baseline and differential
GenevisibleiP46108 HS

Organism-specific databases

HPAiCAB010485
HPA068087

Interactioni

Subunit structurei

Interacts with ABL1, C3G, DOCK3, DOCK5, 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. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases.16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytoskeletal protein binding Source: Ensembl
  • ephrin receptor binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: Ensembl
  • phosphotyrosine residue binding Source: CAFA
  • protein phosphorylated amino acid binding Source: CAFA
  • protein self-association Source: CAFA
  • protein tyrosine kinase binding Source: CAFA
  • scaffold protein binding Source: Ensembl
  • SH2 domain binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: CAFA
  • SH3 domain binding Source: CAFA

Protein-protein interaction databases

BioGridi107788, 255 interactors
CORUMiP46108
DIPiDIP-199N
IntActiP46108, 279 interactors
MINTiP46108
STRINGi9606.ENSP00000300574

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 13Combined sources7
Beta strandi14 – 16Combined sources3
Helixi20 – 27Combined sources8
Beta strandi30 – 33Combined sources4
Beta strandi34 – 39Combined sources6
Beta strandi41 – 43Combined sources3
Beta strandi46 – 52Combined sources7
Beta strandi54 – 56Combined sources3
Beta strandi57 – 63Combined sources7
Beta strandi66 – 69Combined sources4
Beta strandi70 – 77Combined sources8
Turni78 – 80Combined sources3
Beta strandi87 – 89Combined sources3
Beta strandi92 – 96Combined sources5
Helixi97 – 106Combined sources10
Beta strandi109 – 112Combined sources4
Beta strandi116 – 118Combined sources3
Beta strandi120 – 123Combined sources4
Helixi126 – 128Combined sources3
Beta strandi135 – 141Combined sources7
Beta strandi146 – 150Combined sources5
Beta strandi158 – 163Combined sources6
Beta strandi165 – 173Combined sources9
Beta strandi179 – 183Combined sources5
Helixi184 – 186Combined sources3
Beta strandi187 – 190Combined sources4
Beta strandi208 – 210Combined sources3
Beta strandi224 – 227Combined sources4
Beta strandi229 – 231Combined sources3
Beta strandi239 – 242Combined sources4
Beta strandi253 – 255Combined sources3
Beta strandi260 – 269Combined sources10
Beta strandi273 – 279Combined sources7
Beta strandi282 – 287Combined sources6
Helixi288 – 290Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JU5NMR-A12-120[»]
2DVJNMR-A1-228[»]
2EYVNMR-A6-124[»]
2EYWNMR-A125-198[»]
2EYXNMR-A232-298[»]
2EYYNMR-A1-204[»]
2EYZNMR-A1-304[»]
2MS4NMR-B216-224[»]
5UL6X-ray1.45A134-191[»]
DisProtiDP00748
DP00973
ProteinModelPortaliP46108
SMRiP46108
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46108

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 118SH2PROSITE-ProRule annotationAdd BLAST106
Domaini132 – 192SH3 1PROSITE-ProRule annotationAdd BLAST61
Domaini235 – 296SH3 2PROSITE-ProRule annotationAdd BLAST62

Domaini

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.

Sequence similaritiesi

Belongs to the CRK family.Curated

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4792 Eukaryota
ENOG4110574 LUCA
GeneTreeiENSGT00820000127055
HOGENOMiHOG000236288
HOVERGENiHBG105616
InParanoidiP46108
KOiK04438
OMAiGSWYWGR
OrthoDBiEOG091G0JPQ
PhylomeDBiP46108
TreeFamiTF321436

Family and domain databases

CDDicd11759 SH3_CRK_C, 1 hit
cd11758 SH3_CRK_N, 1 hit
Gene3Di3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR035458 CRK_SH3_C
IPR035457 CRK_SH3_N
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PF07653 SH3_2, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF50044 SSF50044, 3 hits
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Crk-II (identifier: P46108-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS
60 70 80 90 100
VSENSRVSHY IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL
110 120 130 140 150
LEFYKIHYLD TTTLIEPVSR SRQGSGVILR QEEAEYVRAL FDFNGNDEED
160 170 180 190 200
LPFKKGDILR IRDKPEEQWW NAEDSEGKRG MIPVPYVEKY RPASASVSAL
210 220 230 240 250
IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA RVIQKRVPNA
260 270 280 290 300
YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPD

EDFS
Length:304
Mass (Da):33,831
Last modified:July 24, 2007 - v2
Checksum:i4CFBFB65BFC2E265
GO
Isoform Crk-I (identifier: P46108-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     204-204: N → R
     205-304: Missing.

Show »
Length:204
Mass (Da):22,906
Checksum:iB4C5BF23887B6B80
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti109L → W in BAA01505 (PubMed:1630456).Curated1
Sequence conflicti109L → W in AAB28213 (PubMed:8378094).Curated1
Sequence conflicti215G → P in BAA01505 (PubMed:1630456).Curated1
Sequence conflicti215G → P in AAB28213 (PubMed:8378094).Curated1
Sequence conflicti278E → G in BAA01505 (PubMed:1630456).Curated1
Sequence conflicti278E → G in AAB28213 (PubMed:8378094).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041153204N → R in isoform Crk-I. 2 Publications1
Alternative sequenceiVSP_041154205 – 304Missing in isoform Crk-I. 2 PublicationsAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10656 mRNA Translation: BAA01505.1
S65701 Genomic DNA Translation: AAB28213.1
BT007277 mRNA Translation: AAP35941.1
EU332838 Genomic DNA Translation: ABY87527.1
AK291060 mRNA Translation: BAF83749.1
AC032044 Genomic DNA No translation available.
AC100748 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90621.1
CH471108 Genomic DNA Translation: EAW90624.1
CH471108 Genomic DNA Translation: EAW90625.1
BC001718 mRNA Translation: AAH01718.1
BC008506 mRNA Translation: AAH08506.1
BC009837 mRNA Translation: AAH09837.1
CCDSiCCDS11002.1 [P46108-1]
CCDS45561.1 [P46108-2]
PIRiA45022
RefSeqiNP_005197.3, NM_005206.4 [P46108-2]
NP_058431.2, NM_016823.3 [P46108-1]
UniGeneiHs.461896

Genome annotation databases

EnsembliENST00000300574; ENSP00000300574; ENSG00000167193 [P46108-1]
ENST00000398970; ENSP00000381942; ENSG00000167193 [P46108-2]
GeneIDi1398
KEGGihsa:1398
UCSCiuc002fsl.4 human [P46108-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCRK_HUMAN
AccessioniPrimary (citable) accession number: P46108
Secondary accession number(s): A8MWE8
, B0LPE8, D3DTH6, Q96GA9, Q96HJ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 24, 2007
Last modified: June 20, 2018
This is version 196 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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