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] See more...

Aliases for CRKL Gene

Aliases for CRKL Gene

  • CRK Like Proto-Oncogene, Adaptor Protein 2 3 5
  • V-Crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like 2 3
  • Crk-Like Protein 3 4
  • CRKL 5

External Ids for CRKL Gene

Previous GeneCards Identifiers for CRKL Gene

  • GC22P017970
  • GC22P019596
  • GC22P021272
  • GC22P004539

Summaries for CRKL Gene

Entrez Gene Summary for CRKL Gene

  • 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]

CIViC Summary for CRKL Gene

GeneCards Summary for CRKL Gene

CRKL (CRK Like Proto-Oncogene, Adaptor Protein) is a Protein Coding gene. Diseases associated with CRKL include Chromosome 22Q11.2 Deletion Syndrome, Distal and Leukemia, Chronic Myeloid. Among its related pathways are JNK signaling in the CD4+ TCR pathway and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include SH3/SH2 adaptor activity. An important paralog of this gene is CRK.

UniProtKB/Swiss-Prot Summary for CRKL Gene

Gene Wiki entry for CRKL Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CRKL Gene

Genomics for CRKL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CRKL Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CRKL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CRKL

Top Transcription factor binding sites by QIAGEN in the CRKL gene promoter:
  • AP-1
  • AREB6
  • ATF-2
  • c-Jun
  • MRF-2
  • PPAR-alpha
  • STAT1
  • STAT1alpha
  • STAT1beta
  • XBP-1

Genomic Locations for CRKL Gene

Genomic Locations for CRKL Gene
chr22:20,917,407-20,953,747
(GRCh38/hg38)
Size:
36,341 bases
Orientation:
Plus strand
chr22:21,271,714-21,308,037
(GRCh37/hg19)
Size:
36,324 bases
Orientation:
Plus strand

Genomic View for CRKL Gene

Genes around CRKL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CRKL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CRKL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRKL Gene

Proteins for CRKL Gene

  • Protein details for CRKL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P46109-CRKL_HUMAN
    Recommended name:
    Crk-like protein
    Protein Accession:
    P46109
    Secondary Accessions:
    • A8KA44
    • D3DX35

    Protein attributes for CRKL Gene

    Size:
    303 amino acids
    Molecular mass:
    33777 Da
    Quaternary structure:
    • Interacts with tyrosine-phosphorylated EPOR and INPP5D/SHIP1 (PubMed:11443118). Interacts with DOCK2 and DOCK5 via its first SH3 domain (PubMed:12393632, PubMed:19004829). Interacts with phosphorylated CBLB and IRS4 (PubMed:10022120, PubMed:9614078).

    Three dimensional structures from OCA and Proteopedia for CRKL Gene

neXtProt entry for CRKL Gene

Post-translational modifications for CRKL Gene

  • Ubiquitination at Lys292
  • Modification sites at PhosphoSitePlus

Other Protein References for CRKL Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for CRKL

No data available for DME Specific Peptides for CRKL Gene

Domains & Families for CRKL Gene

Gene Families for CRKL Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CRKL Gene

InterPro:
Blocks:
  • SH2 domain signature
  • SH3 domain signature
  • Variant SH3
ProtoNet:

Suggested Antigen Peptide Sequences for CRKL Gene

GenScript: Design optimal peptide antigens:
  • Crk-like protein (CRKL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P46109

UniProtKB/Swiss-Prot:

CRKL_HUMAN :
  • Belongs to the CRK family.
Family:
  • Belongs to the CRK family.
genes like me logo Genes that share domains with CRKL: view

Function for CRKL Gene

Molecular function for CRKL Gene

UniProtKB/Swiss-Prot Function:
May mediate the transduction of intracellular signals.
GENATLAS Biochemistry:
avian sarcoma virus CT10 (v-crk) related

Phenotypes From GWAS Catalog for CRKL Gene

Gene Ontology (GO) - Molecular Function for CRKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IPI 20624904
GO:0003723 RNA binding HDA 22658674
GO:0005070 SH3/SH2 adaptor activity TAS --
GO:0005515 protein binding IPI 8626543
GO:0042802 identical protein binding IPI 17161365
genes like me logo Genes that share ontologies with CRKL: view
genes like me logo Genes that share phenotypes with CRKL: view

Human Phenotype Ontology for CRKL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CRKL Gene

MGI Knock Outs for CRKL:

Animal Model Products

CRISPR Products

miRNA for CRKL Gene

miRTarBase miRNAs that target CRKL

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CRKL

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CRKL Gene

Localization for CRKL Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CRKL gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 4
extracellular 2
cytoskeleton 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CRKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol TAS --
GO:0031594 neuromuscular junction IEA --
GO:0032991 protein-containing complex IEA --
GO:0045202 synapse IEA --
genes like me logo Genes that share ontologies with CRKL: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CRKL Gene

Pathways & Interactions for CRKL Gene

genes like me logo Genes that share pathways with CRKL: view

Pathways by source for CRKL Gene

10 GeneGo (Thomson Reuters) pathways for CRKL Gene
  • Chemotaxis CXCR4 signaling pathway
  • Development EPO-induced Jak-STAT pathway
  • Development EPO-induced MAPK pathway
  • Development Flt3 signaling
  • Development HGF signaling pathway
5 Qiagen pathways for CRKL Gene
  • HGF Pathway
  • Internalin Pathway
  • JNK Pathway
  • MAPK Family Pathway
  • Rap1 Pathway
1 Cell Signaling Technology pathway for CRKL Gene

SIGNOR curated interactions for CRKL Gene

Activates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CRKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000186 activation of MAPKK activity TAS --
GO:0000187 activation of MAPK activity IEA --
GO:0001558 regulation of cell growth IEA --
GO:0001568 blood vessel development IEA --
GO:0001655 urogenital system development IEA --
genes like me logo Genes that share ontologies with CRKL: view

Drugs & Compounds for CRKL Gene

(6) Drugs for CRKL Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for CRKL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CRKL: view

Transcripts for CRKL Gene

mRNA/cDNA for CRKL Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CRKL

Alternative Splicing Database (ASD) splice patterns (SP) for CRKL Gene

No ASD Table

Relevant External Links for CRKL Gene

GeneLoc Exon Structure for
CRKL

Expression for CRKL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CRKL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CRKL Gene

This gene is overexpressed in Peripheral blood mononuclear cells (14.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CRKL Gene



Protein tissue co-expression partners for CRKL Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CRKL

SOURCE GeneReport for Unigene cluster for CRKL Gene:

Hs.5613

Evidence on tissue expression from TISSUES for CRKL Gene

  • Nervous system(4.5)
  • Liver(4.5)
  • Skin(4.5)
  • Spleen(4.5)
  • Blood(2.9)
  • Bone marrow(2.8)
  • Muscle(2.7)
  • Kidney(2.7)
  • Stomach(2.7)
  • Heart(2.7)
  • Intestine(2.5)
  • Lymph node(2.4)
  • Lung(2.2)
  • Thyroid gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CRKL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeleton
Regions:
Head and neck:
  • brain
  • chin
  • ear
  • eye
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • outer ear
  • skull
Thorax:
  • aorta
  • heart
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
General:
  • blood
  • blood vessel
  • hair
  • skin
genes like me logo Genes that share expression patterns with CRKL: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for CRKL Gene

Orthologs for CRKL Gene

This gene was present in the common ancestor of animals.

Orthologs for CRKL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CRKL 30 31
  • 99.78 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CRKL 30 31
  • 95.05 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Crkl 30
  • 91.53 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia CRKL 31
  • 91 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Crkl 30 17 31
  • 90.54 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CRKL 31
  • 89 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia CRKL 31
  • 81 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CRKL 30 31
  • 83.72 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 62 (a)
ManyToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia crkl 30
  • 76.44 (n)
Zebrafish
(Danio rerio)
Actinopterygii crkl 30 31
  • 72.33 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Crk 31 32
  • 48 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea ced-2 31
  • 31 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.6350 31
  • 50 (a)
OneToMany
Species where no ortholog for CRKL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for CRKL Gene

ENSEMBL:
Gene Tree for CRKL (if available)
TreeFam:
Gene Tree for CRKL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CRKL: view image

Paralogs for CRKL Gene

Paralogs for CRKL Gene

(2) SIMAP similar genes for CRKL Gene using alignment to 2 proteins:

  • CRKL_HUMAN
  • L8E7R7_HUMAN
genes like me logo Genes that share paralogs with CRKL: view

Variants for CRKL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CRKL Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
733871 Likely Benign: not provided 20,934,166(+) A/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
735924 Likely Benign: not provided 20,918,183(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
740575 Likely Benign: not provided 20,949,722(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
756908 Likely Benign: not provided 20,934,001(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
770308 Benign: not provided 20,934,128(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT

Additional dbSNP identifiers (rs#s) for CRKL Gene

Structural Variations from Database of Genomic Variants (DGV) for CRKL Gene

Variant ID Type Subtype PubMed ID
dgv4483n100 CNV gain 25217958
dgv4484n100 CNV gain 25217958
dgv4485n100 CNV gain 25217958
dgv7993n54 CNV gain 21841781
dgv7994n54 CNV gain 21841781
esv2678175 CNV deletion 23128226
esv2763693 CNV gain 21179565
esv3647304 CNV loss 21293372
esv3647305 CNV gain 21293372
esv3893441 CNV gain+loss 25118596
nsv1056614 CNV loss 25217958
nsv1065617 CNV gain 25217958
nsv1066625 CNV gain 25217958
nsv1123578 CNV deletion 24896259
nsv436864 CNV insertion 17901297
nsv523162 CNV loss 19592680
nsv588305 CNV loss 21841781
nsv834140 CNV loss 17160897
nsv834141 CNV loss 17160897

Variation tolerance for CRKL Gene

Residual Variation Intolerance Score: 20.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.78; 16.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CRKL Gene

Human Gene Mutation Database (HGMD)
CRKL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CRKL

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CRKL Gene

Disorders for CRKL Gene

MalaCards: The human disease database

(15) MalaCards diseases for CRKL Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
chromosome 22q11.2 deletion syndrome, distal
  • distal chromosome 22q11.2 deletion syndrome
leukemia, chronic myeloid
  • cml
sarcoma
  • connective and soft tissue neoplasm
papillary thyroid microcarcinoma
digeorge syndrome
  • cayler cardiofacial syndrome
- elite association - COSMIC cancer census association via MalaCards
Search CRKL in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CRKL

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CRKL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CRKL Gene

Publications for CRKL Gene

  1. Isolation and chromosomal localization of CRKL, a human crk-like gene. (PMID: 8361759) ten Hoeve J … Groffen J (Oncogene 1993) 2 3 4 23
  2. DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV. (PMID: 19004829) Sanders MA … Basson MD (The Journal of biological chemistry 2009) 3 4 23
  3. DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines. (PMID: 12393632) Nishihara H … Tanaka S (Blood 2002) 3 4 23
  4. CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling. (PMID: 11443118) Arai A … Miura O (The Journal of biological chemistry 2001) 3 4 23
  5. Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. (PMID: 10022120) Elly C … Liu YC (Oncogene 1999) 3 4 23

Products for CRKL Gene

  • Addgene plasmids for CRKL
  • Signalway ELISA kits for CRKL

Sources for CRKL Gene