CRKL Gene

HGNC Family	SH2 domain containing
Name	v-crk avian sarcoma virus CT10 oncogene homolog-like
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CRKL is a versatile adaptor protein that orchestrates the transmission of signals from activated receptor tyrosine kinases to diverse downstream pathways, thereby regulating processes as varied as cytoskeletal remodeling, cell adhesion, migration, differentiation, and survival. In T lymphocytes, for example, CRKL interacts with key partners such as WIP and is incorporated into complexes (with C3G) that facilitate Rap1 activation, integrin clustering, and immunological synapse formation—all critical events for optimal T cell activation and actin reorganization ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "). In gastric epithelial cells, the Helicobacter pylori effector protein CagA specifically binds to CRKL (along with other Crk family members), which is essential for disrupting adherens junctions and promoting cell scattering, thereby illustrating how pathogens co‐opt host adaptor proteins to alter cellular behavior ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "). In the developing nervous system, CRKL—acting downstream of Dab1 in the Reelin pathway—contributes to proper neuronal migration and cortical lamination, underscoring its importance in neurodevelopment ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "). Furthermore, at the neuromuscular junction, CRKL is recruited by Dok-7 to drive both pre- and postsynaptic differentiation, a function critical for synapse formation and muscle innervation ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "). In neuronal cells, CRKL also participates in neurotrophin signaling complexes—together with other adaptor proteins—to modulate Rho GTPase activity and support neurite outgrowth ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "). Finally, influenza A virus nonstructural protein NS1 exploits CRKL binding to enhance phosphatidylinositol 3-kinase/Akt signaling, highlighting a role for CRKL in pathogen-induced modulation of host cell survival pathways ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ").\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies emphasize that CRKL functions as a central scaffold linking activated receptors to key intracellular signaling circuits. Its ability to integrate multiple upstream signals and coordinate actin dynamics and adhesion processes renders it indispensable in both normal physiology—such as immune synapse formation, neuromuscular development, and neuronal migration—and in pathological conditions where its misregulation is exploited by infectious agents.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yoji Sasahara, Rima Rachid, Michael J Byrne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00728-1"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00728-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12504004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12504004"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeffrey C Nolz, Lucas P Nacusi, Colin M Segovis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200801121"}], "href": "https://doi.org/10.1083/jcb.200801121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18809728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18809728"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masato Suzuki, Hitomi Mimuro, Toshihiko Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20051027"}], "href": "https://doi.org/10.1084/jem.20051027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16275761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16275761"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tae-Ju Park, Tom Curran "}, {"type": "b", "children": [{"type": "t", "text": "Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4323-08.2008"}], "href": "https://doi.org/10.1523/JNEUROSCI.4323-08.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19074029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19074029"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Peter T Hallock, Chong-Feng Xu, Tae-Ju Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1977710"}], "href": "https://doi.org/10.1101/gad.1977710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21041412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21041412"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Takeshi Nakamura, Misako Komiya, Kiyoaki Sone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.24.8721-8734.2002"}], "href": "https://doi.org/10.1128/MCB.22.24.8721-8734.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12446789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12446789"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Leena S Heikkinen, Arunas Kazlauskas, Krister Melén, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707195200"}], "href": "https://doi.org/10.1074/jbc.M707195200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18165234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18165234"}]}]}]}
Proteins	CRKL_HUMAN
NCBI Gene ID	1399
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRKL has 9,826 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 129 datasets.

Click the + buttons to view associations for CRKL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CRKL Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CRKL gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRKL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRKL gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CRKL gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CRKL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CRKL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRKL gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CRKL protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CRKL gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRKL gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRKL gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CRKL gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRKL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CRKL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CRKL gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CRKL protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CRKL gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRKL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRKL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CRKL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CRKL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRKL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CRKL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRKL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CRKL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CRKL protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRKL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRKL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRKL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRKL gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CRKL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRKL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CRKL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CRKL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRKL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CRKL gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRKL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CRKL gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CRKL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CRKL gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.