CRKL CRK like proto-oncogene, adaptor protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRKLprovided by HGNC
Official Full Name: CRK like proto-oncogene, adaptor proteinprovided by HGNC
Primary source: HGNC:HGNC:2363
See related: Ensembl:ENSG00000099942 MIM:602007
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: 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]
Expression: Ubiquitous expression in brain (RPKM 22.4), bone marrow (RPKM 22.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.21

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	22	NC_000022.11 (20917407..20953747)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (21271695..21308035)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Quantitative assessment of glioblastoma phenotypes in vitro establishes cell migration as a robust readout of Crk and CrkL activity.
Title: Quantitative assessment of glioblastoma phenotypes in vitro establishes cell migration as a robust readout of Crk and CrkL activity.
Bifunctional Role of CrkL during Bone Remodeling.
Title: Bifunctional Role of CrkL during Bone Remodeling.
Novel role for CRK adaptor proteins as essential components of SRC/FAK signaling for epithelial-mesenchymal transition and colorectal cancer aggressiveness.
Title: Novel role for CRK adaptor proteins as essential components of SRC/FAK signaling for epithelial-mesenchymal transition and colorectal cancer aggressiveness.
CRKL promotes proliferation, migration, invasion of laryngeal squamous cell carcinoma.
Title: CRKL promotes proliferation, migration, invasion of laryngeal squamous cell carcinoma.
Downregulated miR29a promotes B cell overactivation by upregulating Crklike protein in systemic lupus erythematosus.
Title: Downregulated miR‑29a promotes B cell overactivation by upregulating Crk‑like protein in systemic lupus erythematosus.
miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway.
Title: miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway.
Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function.
Title: Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function.
A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.
Title: A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.
Copy number gains of the putative CRKL oncogene in laryngeal squamous cell carcinoma result in strong nuclear expression of the protein and influence cell proliferation and migration.
Title: Copy number gains of the putative CRKL oncogene in laryngeal squamous cell carcinoma result in strong nuclear expression of the protein and influence cell proliferation and migration.
LncRNA FAL1 promotes the development of oral squamous cell carcinoma through regulating the microRNA-761/CRKL pathway.
Title: LncRNA FAL1 promotes the development of oral squamous cell carcinoma through regulating the microRNA-761/CRKL pathway.

Submit: New GeneRIF Correction See all GeneRIFs (83)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-04-13) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2020-04-13) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46189 (e-PCR)
- UniSTS:50453

D8S2279 (e-PCR)
- UniSTS:473907

D22S1018E (e-PCR)
- UniSTS:88630

D22S1687 (e-PCR)
- UniSTS:23128

RH77782 (e-PCR)
- UniSTS:23129

RH27792 (e-PCR)
- UniSTS:89767

STS-X59656 (e-PCR)
- UniSTS:63670

D22S1020E (e-PCR)
- UniSTS:88523

A004M48 (e-PCR)
- UniSTS:77265

GDB:452608 (e-PCR)
- UniSTS:62448

Homology

Homologs of the CRKL gene: The CRKL gene is conserved in chimpanzee, Rhesus monkey, dog, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 391 organisms have orthologs with human gene CRKL
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in JNK cascade	TAS Traceable Author Statement more info	PubMed
involved_in Ras protein signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in acetylcholine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in activation of GTPase activity	IEA Inferred from Electronic Annotation more info
involved_in anterior/posterior pattern specification	IEA Inferred from Electronic Annotation more info
involved_in blood vessel development	IEA Inferred from Electronic Annotation more info
involved_in cell chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cellular response to interleukin-7	IEA Inferred from Electronic Annotation more info
involved_in cellular response to transforming growth factor beta stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in cerebellar neuron development	IEA Inferred from Electronic Annotation more info
involved_in cerebral cortex development	IEA Inferred from Electronic Annotation more info
involved_in cranial skeletal system development	IEA Inferred from Electronic Annotation more info
involved_in dendrite development	IEA Inferred from Electronic Annotation more info
involved_in endothelin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in establishment of cell polarity	IEA Inferred from Electronic Annotation more info
involved_in fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in helper T cell diapedesis	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in outflow tract morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in parathyroid gland development	IEA Inferred from Electronic Annotation more info
involved_in pharynx development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in reelin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of T cell migration	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell adhesion mediated by integrin	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in regulation of dendrite development	IEA Inferred from Electronic Annotation more info
involved_in regulation of skeletal muscle acetylcholine-gated channel clustering	IEA Inferred from Electronic Annotation more info
involved_in retinoic acid receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in single fertilization	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in synapse assembly	IEA Inferred from Electronic Annotation more info
involved_in thymus development	IEA Inferred from Electronic Annotation more info
involved_in urogenital system development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extrinsic component of postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in neuromuscular junction	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: crk-like protein

Names: v-crk avian sarcoma virus CT10 oncogene homolog-like

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016354.1 RefSeqGene

Range

4982..41322

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005207.4 → NP_005198.1 crk-like protein

See identical proteins and their annotated locations for NP_005198.1

Status: REVIEWED

Source sequence(s)

AA844269, AC002470, BC043500, X59656

Consensus CDS

CCDS13785.1

UniProtKB/Swiss-Prot

P46109

Related

ENSP00000346300.3, ENST00000354336.8

Conserved Domains (3) summary

cd09926
Location:6 → 106

SH2_CRK_like; Src homology 2 domain found in cancer-related signaling adaptor protein CRK

cd11758
Location:126 → 180

SH3_CRK_N; N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins

cd11759
Location:237 → 293

SH3_CRK_C; C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins