Human Gene CRKL (uc002ztf.2) Description and Page Index
  Description: Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian)-like (CRKL), mRNA.
RefSeq Summary (NM_005207): This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803613.144276.1, SRR1803615.104356.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000354336.8/ ENSP00000346300.3 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr22:21,271,714-21,308,037 Size: 36,324 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg19 chr22:21,272,223-21,304,133 Size: 31,911 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr22:21,271,714-21,308,037)mRNA (may differ from genome)Protein (303 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Crk-like protein;
FUNCTION: May mediate the transduction of intracellular signals.
SUBUNIT: Interacts with INPP5D/SHIP1. Interacts with DOCK2 and EPOR. Interacts with phosphorylated CBLB and IRS4.
INTERACTION: Q9EQG6:Kidins220 (xeno); NbExp=2; IntAct=EBI-910, EBI-976654; Q92918:MAP4K1; NbExp=5; IntAct=EBI-910, EBI-881;
SIMILARITY: Belongs to the CRK family.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 2 SH3 domains.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CRKL
CDC HuGE Published Literature: CRKL

-  MalaCards Disease Associations
  MalaCards Gene Search: CRKL
Diseases sorted by gene-association score: chromosome 22q11.2 deletion syndrome, distal* (14), leukemia, chronic myeloid, somatic (10), chromosome 6pter-p24 deletion syndrome (8), sarcoma (7), agnathia-otocephaly complex (5), velocardiofacial syndrome (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C545373 AP24534
  • D004958 Estradiol
  • C488369 dasatinib
  • C111237 vorinostat
  • C479799 (E)-4-((2-N-(4-methoxybenzenesulfonyl)amino)stilbazole)1-oxide
  • D015056 1-Methyl-3-isobutylxanthine
  • C498826 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • C012606 4-vinyl-1-cyclohexene dioxide
  • D000082 Acetaminophen
  • D000255 Adenosine Triphosphate
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 28.77 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 819.80 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -262.60509-0.516 Picture PostScript Text
3' UTR -1254.613904-0.321 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

- X-ray MuPIT

- X-ray MuPIT

To conserve bandwidth, only the images from the first 3 structures are shown.

ModBase Predicted Comparative 3D Structure on P46109
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 orthologGenome BrowserGenome BrowserNo orthologNo ortholog
   Gene Details  
   Gene Sorter  
  Protein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001784 phosphotyrosine binding
GO:0003723 RNA binding
GO:0004871 signal transducer activity
GO:0005070 SH3/SH2 adaptor activity
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0045296 cadherin binding

Biological Process:
GO:0000186 activation of MAPKK activity
GO:0001568 blood vessel development
GO:0007254 JNK cascade
GO:0007265 Ras protein signal transduction
GO:0007389 pattern specification process
GO:0007507 heart development
GO:0008284 positive regulation of cell proliferation
GO:0009887 animal organ morphogenesis
GO:0009952 anterior/posterior pattern specification
GO:0019221 cytokine-mediated signaling pathway
GO:0035556 intracellular signal transduction
GO:0048538 thymus development
GO:0060017 parathyroid gland development
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading

Cellular Component:
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  AK292909 - Homo sapiens cDNA FLJ77301 complete cds, highly similar to Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian)-like (CRKL), mRNA.
X59656 - H.sapiens crk-like gene CRKL.
BC026248 - Homo sapiens, v-crk sarcoma virus CT10 oncogene homolog (avian)-like, clone IMAGE:4808983, mRNA.
JD282852 - Sequence 263876 from Patent EP1572962.
BC043500 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian)-like, mRNA (cDNA clone MGC:49914 IMAGE:6046673), complete cds.
JD399452 - Sequence 380476 from Patent EP1572962.
CR456423 - Homo sapiens CRKL full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.CRKL).
JD422452 - Sequence 403476 from Patent EP1572962.
JD458451 - Sequence 439475 from Patent EP1572962.
CU013272 - Homo sapiens CRKL, mRNA (cDNA clone IMAGE:100000049), complete cds, without stop codon, in Gateway system.
CU012984 - Homo sapiens CRKL, mRNA (cDNA clone IMAGE:100000145), complete cds, with stop codon, in Gateway system.
AB463342 - Synthetic construct DNA, clone: pF1KB8444, Homo sapiens CRKL gene for v-crk sarcoma virus CT10 oncogene homolog, without stop codon, in Flexi system.
HV542942 - JP 2011525491-A/27: CRKL TARGETING PEPTIDES.
JA083023 - Sequence 58 from Patent EP2303913.
JD550461 - Sequence 531485 from Patent EP1572962.
DQ586321 - Homo sapiens piRNA piR-53433, complete sequence.
JD161359 - Sequence 142383 from Patent EP1572962.
JD290695 - Sequence 271719 from Patent EP1572962.
JD260678 - Sequence 241702 from Patent EP1572962.
JD053352 - Sequence 34376 from Patent EP1572962.
JD060312 - Sequence 41336 from Patent EP1572962.
JD059502 - Sequence 40526 from Patent EP1572962.
JD049856 - Sequence 30880 from Patent EP1572962.
JD215378 - Sequence 196402 from Patent EP1572962.
JD204069 - Sequence 185093 from Patent EP1572962.
JD156634 - Sequence 137658 from Patent EP1572962.
JD429480 - Sequence 410504 from Patent EP1572962.
JD300494 - Sequence 281518 from Patent EP1572962.
JD094815 - Sequence 75839 from Patent EP1572962.
JD342141 - Sequence 323165 from Patent EP1572962.
JD480419 - Sequence 461443 from Patent EP1572962.
DQ590021 - Homo sapiens piRNA piR-57133, complete sequence.
DQ590022 - Homo sapiens piRNA piR-57134, complete sequence.
JD182176 - Sequence 163200 from Patent EP1572962.
JD245760 - Sequence 226784 from Patent EP1572962.
JD308190 - Sequence 289214 from Patent EP1572962.
JD254808 - Sequence 235832 from Patent EP1572962.
JD254809 - Sequence 235833 from Patent EP1572962.
JD514004 - Sequence 495028 from Patent EP1572962.
JD069825 - Sequence 50849 from Patent EP1572962.
JD311877 - Sequence 292901 from Patent EP1572962.
DQ598791 - Homo sapiens piRNA piR-36857, complete sequence.
AK000311 - Homo sapiens cDNA FLJ20304 fis, clone HEP06749.
JD314188 - Sequence 295212 from Patent EP1572962.
BC044621 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian)-like, mRNA (cDNA clone IMAGE:5273862).
BC053958 - Homo sapiens v-crk sarcoma virus CT10 oncogene homolog (avian)-like, mRNA (cDNA clone IMAGE:5273798).
BC033281 - Homo sapiens, clone IMAGE:4749267, mRNA.
JD394708 - Sequence 375732 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04012 - ErbB signaling pathway
hsa04062 - Chemokine signaling pathway
hsa04510 - Focal adhesion
hsa04666 - Fc gamma R-mediated phagocytosis
hsa04722 - Neurotrophin signaling pathway
hsa04810 - Regulation of actin cytoskeleton
hsa04910 - Insulin signaling pathway
hsa05100 - Bacterial invasion of epithelial cells
hsa05131 - Shigellosis
hsa05200 - Pathways in cancer
hsa05211 - Renal cell carcinoma
hsa05220 - Chronic myeloid leukemia

BioCarta from NCI Cancer Genome Anatomy Project
h_integrinPathway - Integrin Signaling Pathway
h_metPathway - Signaling of Hepatocyte Growth Factor Receptor
h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec
h_pyk2Pathway - Links between Pyk2 and Map Kinases
h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation

Reactome (by CSHL, EBI, and GO)

Protein P46109 (Reactome details) participates in the following event(s):

R-HSA-170975 p-FRS2 binds CRKL
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-170978 Phospho-Frs2:CrkL binds C3G
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-170979 (Frs2)C3G stimulates nucleotide exchange on Rap1
R-HSA-8875568 RAPGEF1 activates RAP1
R-HSA-170968 Frs2-mediated activation
R-HSA-186763 Downstream signal transduction
R-HSA-912631 Regulation of signaling by CBL
R-HSA-8875555 MET activates RAP1 and RAC1
R-HSA-169893 Prolonged ERK activation events
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-187687 Signalling to ERKs
R-HSA-6806834 Signaling by MET
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-449147 Signaling by Interleukins
R-HSA-187037 Signaling by NTRK1 (TRKA)
R-HSA-162582 Signal Transduction
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-166520 Signaling by NTRKs
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8KA44, CRKL_HUMAN, D3DX35, NM_005207, NP_005198, P46109
UCSC ID: uc002ztf.2
RefSeq Accession: NM_005207
Protein: P46109 (aka CRKL_HUMAN)
CCDS: CCDS13785.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_005207.3
exon count: 3CDS single in 3' UTR: no RNA size: 5336
ORF size: 912CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1976.00frame shift in genome: no % Coverage: 99.79
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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.