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

Genomic context

Location:: 22q11.21

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	22	NC_000022.11 (20917407..20953747)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (21271714..21308037)

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?

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.
MiR-335 suppresses cell proliferation and migration by upregulating CRKL in bladder cancer.
Title: MiR-335 suppresses cell proliferation and migration by upregulating CRKL in bladder cancer.
High CRKL expression is associated with gastric cancer.
Title: Overexpression of CrkL as a novel biomarker for poor prognosis in gastric cancer.
This is the first report of CRKL-regulation of the alternative splicing of a number of genes critical in tumorigenesis and cancer progression, which is consistent with CRKL reported role as a signaling adaptor and a kinase.
Title: CRKL regulates alternative splicing of cancer-related genes in cervical cancer samples and HeLa cell.
SASH1 is an inhibitor of CRKL-mediated SRC signaling.
Title: The Tumor Suppressor SASH1 Interacts With the Signal Adaptor CRKL to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer.
Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-epithelial mesenchymal transition pathway.
Title: miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition.
High CRKL expression is associated with Cervical Cancer.
Title: MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL).
Silencing CRKL expression in PTEN-null human cancer cells leads to a decrease in p110beta-dependent PI3K signaling and cell proliferation.
Title: CRKL Mediates p110β-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells.
Study found the expression of CRKL up-regulated and correlated with that of ABCG2 in gastric neoplasm. CRKL is one of the downstream molecules regulated by ABCG2, which promotes cell growth.
Title: ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining.
We demonstrated that CRKL is a novel downstream effector of ALK signaling in non-small-cell lung cancer
Title: CRKL mediates EML4-ALK signaling and is a potential therapeutic target for ALK-rearranged lung adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (74)

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: 319 organisms have orthologs with human gene CRKL
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA binding	HDA more info	PubMed
cadherin binding	HDA more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

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

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