Human Gene CRK (ENST00000300574.3_7) from GENCODE V47lift37
  Description: CRK proto-oncogene, adaptor protein, transcript variant II (from RefSeq NM_016823.4)
Gencode Transcript: ENST00000300574.3_7
Gencode Gene: ENSG00000167193.8_9
Transcript (Including UTRs)
   Position: hg19 chr17:1,323,987-1,359,526 Size: 35,540 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg19 chr17:1,326,807-1,359,411 Size: 32,605 Coding Exon Count: 3 

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Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:1,323,987-1,359,526)mRNA (may differ from genome)Protein (304 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CRK_HUMAN
DESCRIPTION: RecName: Full=Adapter molecule crk; AltName: Full=Proto-oncogene c-Crk; AltName: Full=p38;
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: 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. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1.
INTERACTION: P42684:ABL2; NbExp=5; IntAct=EBI-886, EBI-1102694; O15085:ARHGEF11; NbExp=2; IntAct=EBI-886, EBI-311099; Q9ULH1:ASAP1; NbExp=2; IntAct=EBI-886, EBI-346622; P54253:ATXN1; NbExp=2; IntAct=EBI-886, EBI-930964; P56945:BCAR1; NbExp=2; IntAct=EBI-886, EBI-702093; P21333:FLNA; NbExp=2; IntAct=EBI-886, EBI-350432; Q14315:FLNC; NbExp=2; IntAct=EBI-886, EBI-489954; Q92918:MAP4K1; NbExp=3; IntAct=EBI-886, EBI-881; Q9Y4K4:MAP4K5; NbExp=5; IntAct=EBI-886, EBI-1279; P20774:OGN; NbExp=2; IntAct=EBI-886, EBI-1753690; P29074:PTPN4; NbExp=3; IntAct=EBI-886, EBI-710431; Q13905:RAPGEF1; NbExp=3; IntAct=EBI-886, EBI-976876; Q9UPX8:SHANK2; NbExp=2; IntAct=EBI-886, EBI-1570571; O60493:SNX3; NbExp=2; IntAct=EBI-886, EBI-727209; Q07889:SOS1; NbExp=2; IntAct=EBI-886, EBI-297487; Q07890:SOS2; NbExp=2; IntAct=EBI-886, EBI-298181;
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By similarity). Note=Translocated to the plasma membrane upon cell adhesion (By similarity).
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).
DOMAIN: The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB.
PTM: Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. Isoform Crk-II is phosphorylated by KIT.
PTM: 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.
PTM: 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).
SIMILARITY: Belongs to the CRK family.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 2 SH3 domains.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CRK
Diseases sorted by gene-association score: chromosome 17p13.3, centromeric, duplication syndrome (9), sarcoma (8), avian influenza (8), shigellosis (7), miller-dieker lissencephaly syndrome (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 26.50 RPKM in Cells - Cultured fibroblasts
Total median expression: 844.65 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -59.70115-0.519 Picture PostScript Text
3' UTR -781.502820-0.277 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000980 - SH2
IPR011511 - SH3_2
IPR001452 - SH3_domain

Pfam Domains:
PF00017 - SH2 domain
PF00018 - SH3 domain
PF07653 - Variant SH3 domain
PF14604 - Variant SH3 domain

SCOP Domains:
50044 - SH3-domain
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1JU5 - NMR MuPIT 2DVJ - NMR MuPIT 2EYV - NMR MuPIT 2EYW - NMR MuPIT 2EYX - NMR MuPIT 2EYY - NMR MuPIT 2EYZ - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P46108
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001784 phosphotyrosine binding
GO:0005070 SH3/SH2 adaptor activity
GO:0005159 insulin-like growth factor receptor binding
GO:0005515 protein binding
GO:0008092 cytoskeletal protein binding
GO:0017124 SH3 domain binding
GO:0019899 enzyme binding
GO:0019904 protein domain specific binding
GO:0030674 protein binding, bridging
GO:0042169 SH2 domain binding
GO:0043621 protein self-association
GO:0045309 protein phosphorylated amino acid binding
GO:0046875 ephrin receptor binding
GO:0097110 scaffold protein binding
GO:1990782 protein tyrosine kinase binding

Biological Process:
GO:0000186 activation of MAPKK activity
GO:0001878 response to yeast
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0008360 regulation of cell shape
GO:0009966 regulation of signal transduction
GO:0014911 positive regulation of smooth muscle cell migration
GO:0019221 cytokine-mediated signaling pathway
GO:0030307 positive regulation of cell growth
GO:0032956 regulation of actin cytoskeleton organization
GO:0035020 regulation of Rac protein signal transduction
GO:0035728 response to hepatocyte growth factor
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042542 response to hydrogen peroxide
GO:0043087 regulation of GTPase activity
GO:0043393 regulation of protein binding
GO:0045953 negative regulation of natural killer cell mediated cytotoxicity
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0061045 negative regulation of wound healing
GO:0071538 SH2 domain-mediated complex assembly
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071732 cellular response to nitric oxide
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
GO:1901652 response to peptide
GO:1990090 cellular response to nerve growth factor stimulus
GO:1990314 cellular response to insulin-like growth factor stimulus
GO:1990859 cellular response to endothelin
GO:2000146 negative regulation of cell motility
GO:0061041 regulation of wound healing
GO:2000145 regulation of cell motility

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0015629 actin cytoskeleton
GO:0016020 membrane
GO:0032991 macromolecular complex
GO:0045121 membrane raft
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK095449 - Homo sapiens cDNA FLJ38130 fis, clone D6OST2000464.
BC001718 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian), mRNA (cDNA clone MGC:3138 IMAGE:3353237), complete cds.
BC009837 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian), mRNA (cDNA clone MGC:15147 IMAGE:4040536), complete cds.
BC008506 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian), mRNA (cDNA clone MGC:5481 IMAGE:3452137), complete cds.
KR153244 - Homo sapiens Alu_(heterogeneous6)_Ad5_C1 antisense RNA, partial sequence.
AK291060 - Homo sapiens cDNA FLJ77114 complete cds, highly similar to Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian) (CRK), transcript variant I, mRNA.
JD019108 - Sequence 132 from Patent EP1572962.
JD033417 - Sequence 14441 from Patent EP1572962.
D10656 - Homo sapiens mRNA for CRK-II, complete cds.
JD250465 - Sequence 231489 from Patent EP1572962.
JA215688 - Sequence 25 from Patent EP2310507.
JD315774 - Sequence 296798 from Patent EP1572962.
KJ896644 - Synthetic construct Homo sapiens clone ccsbBroadEn_06038 CRK gene, encodes complete protein.
BT007277 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian) mRNA, complete cds.
DQ891147 - Synthetic construct clone IMAGE:100003777; FLH169742.01X; RZPDo839F0896D v-crk sarcoma virus CT10 oncogene homolog (avian) (CRK) gene, encodes complete protein.
DQ894327 - Synthetic construct Homo sapiens clone IMAGE:100008787; FLH169738.01L; RZPDo839F0895D v-crk sarcoma virus CT10 oncogene homolog (avian) (CRK) gene, encodes complete protein.
KU177996 - Homo sapiens v-crk sarcoma virus CT10 oncogene-like protein isoform 1 (CRK) mRNA, partial cds.
KU177997 - Homo sapiens v-crk sarcoma virus CT10 oncogene-like protein isoform 2 (CRK) mRNA, complete cds.
AB528363 - Synthetic construct DNA, clone: pF1KB8151, Homo sapiens CRK gene for v-crk sarcoma virus CT10 oncogene homolog, without stop codon, in Flexi system.
AB061673 - Synthetic construct gene for Picchu-236, complete cds.
AB061674 - Synthetic construct gene for Picchu-236-X, complete cds.
KJ905718 - Synthetic construct Homo sapiens clone ccsbBroadEn_15388 CRK gene, encodes complete protein.
JD407327 - Sequence 388351 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_metPathway - Signaling of Hepatocyte Growth Factor Receptor
h_cxcr4Pathway - CXCR4 Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein P46108 (Reactome details) participates in the following event(s):

R-HSA-372697 Crk binding to p130cas
R-HSA-5218822 CRK binds BCAR1 and or PXN
R-HSA-169891 ARMS:Crk complex binds to active TrkA receptor
R-HSA-2197697 Recruitment of CRKII:DOCK180:ELMO complex to FCGR
R-HSA-8848611 Phosphorylated PXN recruits the CRK complex
R-HSA-5218811 DOCK180:ELMO binds CRK
R-HSA-382056 Crk binds to the active PDGF receptor
R-HSA-912790 CBL binds CRK
R-HSA-8875540 GAB1 recruits CRK,CRKL to MET
R-HSA-169895 Crk's SH3 domain engages C3G
R-HSA-169905 ARMS is phosphorylated by active TrkA receptor
R-HSA-382052 p130Cas and C3G bind PDGFR bound Crk
R-HSA-912734 CBL:CRKL binds RAPGEF1
R-HSA-8875558 RAPGEF1 binds CRK,CRKL
R-HSA-169901 (ARMS)Rap1-GTP binds and activates B-Raf
R-HSA-169904 C3G stimulates nucleotide exchange on Rap1
R-HSA-2029467 Activation of RAC1 by CRKII:DOCK180:ELMO
R-HSA-5218839 DOCK180:ELMO exchanges GTP for GDP, activating RAC1
R-HSA-8848618 Activation of RAC1 by the PXN:CRK complex
R-HSA-8875568 RAPGEF1 activates RAP1
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-170984 ARMS-mediated activation
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-186763 Downstream signal transduction
R-HSA-912631 Regulation of signaling by CBL
R-HSA-8875555 MET activates RAP1 and RAC1
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-194138 Signaling by VEGF
R-HSA-169893 Prolonged ERK activation events
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-8848021 Signaling by PTK6
R-HSA-8875656 MET receptor recycling
R-HSA-186797 Signaling by PDGF
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-8875878 MET promotes cell motility
R-HSA-76009 Platelet Aggregation (Plug Formation)
R-HSA-9006921 Integrin signaling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-187687 Signalling to ERKs
R-HSA-168249 Innate Immune System
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-6806834 Signaling by MET
R-HSA-449147 Signaling by Interleukins
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-162582 Signal Transduction
R-HSA-187037 Signaling by NTRK1 (TRKA)
R-HSA-168256 Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-109582 Hemostasis
R-HSA-166520 Signaling by NTRKs

-  Other Names for This Gene
  Alternate Gene Symbols: A8MWE8, B0LPE8, CRK_HUMAN, D3DTH6, ENST00000300574.1, ENST00000300574.2, NM_016823, P46108, Q96GA9, Q96HJ0, uc317mqa.1, uc317mqa.2
UCSC ID: ENST00000300574.3_7
RefSeq Accession: NM_016823.4
Protein: P46108 (aka CRK_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.