CDC37 Gene

Name	cell division cycle 37
Description	The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Sacchromyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CDC37 is a dedicated kinase‐specific co–chaperone that functions as a scaffold to recruit and load a wide range of protein kinases onto the Hsp90 chaperone machinery. In doing so, CDC37 not only recognizes and binds client kinases via its flexible, dynamic N–terminal domain—but also, through regulated phosphorylation events (e.g., on Ser13 and Tyr298), modulates its own conformation and its interaction with Hsp90 to control the ATPase cycle that is critical for kinase folding, activation, and stabilization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Phosphorylation by kinases such as CK2 at Ser13 is essential for full CDC37 function, enabling the proper assembly of Hsp90–CDC37–kinase complexes and ensuring the efficient progression through the chaperone cycle. Structural and biochemical studies have revealed that the dynamic equilibrium of the CDC37 N–terminal region, which remains partially unfolded, is a key determinant for specifically engaging client kinases, whereas additional phosphorylation events (e.g., at Tyr298) further destabilize parts of CDC37 to facilitate conformational changes in Hsp90 that are required for client release."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CDC37 plays a pivotal role in a variety of signaling pathways by controlling the stability and activity of key kinases involved in cell proliferation, apoptosis, and stress responses. For instance, CDC37 is implicated in the maturation of kinases such as MLK3, CDK4, and FGFR3, which are linked to oncogenic signaling in multiple cancers, as well as neurodegenerative processes when associated with mutated kinases like LRRK2."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, CDC37 has been shown to interact with other signaling mediators such as Vav3, thereby enhancing downstream transcriptional activity and contributing to oncogenic cell proliferation in prostate cancer, while overexpression of CDC37 in colorectal carcinoma supports cell survival through stabilization of key cell cycle regulators like CDK4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the essential role of CDC37 in client quality control, wherein its regulated interactions with both kinases and Hsp90 ensure the proper folding and activation of diverse signaling proteins. This central function makes CDC37 an attractive target for therapeutic strategies aimed at modulating aberrant kinase activity in diseases such as cancer and neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Cara K Vaughan, Ulrich Gohlke, Frank Sobott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of an Hsp90-Cdc37-Cdk4 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2006.07.016"}], "href": "https://doi.org/10.1016/j.molcel.2006.07.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16949366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16949366"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Giuliano Siligardi, Barry Panaretou, Philippe Meyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201287200"}], "href": "https://doi.org/10.1074/jbc.M201287200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11916974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11916974"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wanping Xu, Mehdi Mollapour, Chrisostomos Prodromou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2012.05.015"}], "href": "https://doi.org/10.1016/j.molcel.2012.05.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22727666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22727666"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jieya Shao, Thomas Prince, Steven D Hartson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C300330200"}], "href": "https://doi.org/10.1074/jbc.C300330200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12930845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12930845"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ashleigh B Bachman, Dimitra Keramisanou, Wanping Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-02711-w"}], "href": "https://doi.org/10.1038/s41467-017-02711-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29343704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29343704"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Futoshi Ihama, Mami Yamamoto, Chojiro Kojima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural characterization of the N-terminal kinase-interacting domain of an Hsp90-cochaperone Cdc37 by CD and solution NMR spectroscopy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Proteins Proteom (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbapap.2019.06.007"}], "href": "https://doi.org/10.1016/j.bbapap.2019.06.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31226489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31226489"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hua Zhang, Wei Wu, Yan Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsp90/p50cdc37 is required for mixed-lineage kinase (MLK) 3 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M311377200"}], "href": "https://doi.org/10.1074/jbc.M311377200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15001580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15001580"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chun Yan Wang, Su Tang Guo, Jia Yu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10414"}], "href": "https://doi.org/10.18632/oncotarget.10414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27391062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27391062"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Julia M Eckl, Daniel A Rutz, Veronika Haslbeck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdc37 (cell division cycle 37) restricts Hsp90 (heat shock protein 90) motility by interaction with N-terminal and middle domain binding sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.439257"}], "href": "https://doi.org/10.1074/jbc.M112.439257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23569206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23569206"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Fayi Wu, Stephanie O Peacock, Shuyun Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel interaction between the co-chaperone Cdc37 and Rho GTPase exchange factor Vav3 promotes androgen receptor activity and prostate cancer growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.390963"}], "href": "https://doi.org/10.1074/jbc.M112.390963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23281476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23281476"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jianjun Zhu, Fang Yan, Jia Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cdc37 facilitates cell survival of colorectal carcinoma via activating the CDK4 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.13495"}], "href": "https://doi.org/10.1111/cas.13495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29288563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29288563"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fen Guo, Yue-Qin Li, Shi-Qian Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of mouse Pem protein and cell division cycle 37 homolog."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1745-7270.2005.00102.x"}], "href": "https://doi.org/10.1111/j.1745-7270.2005.00102.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16270159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16270159"}]}]}]}
Synonyms	P50CDC37
Proteins	CDC37_HUMAN
NCBI Gene ID	11140
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CDC37 has 8,887 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 136 datasets.

Click the + buttons to view associations for CDC37 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CDC37 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 CDC37 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 CDC37 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 CDC37 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 CDC37 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 CDC37 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 CDC37 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 CDC37 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CDC37 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 CDC37 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 CDC37 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 CDC37 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDC37 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 CDC37 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CDC37 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CDC37 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 CDC37 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CDC37 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 CDC37 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CDC37 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CDC37 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CDC37 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CDC37 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CDC37 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CDC37 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CDC37 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 CDC37 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 CDC37 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing CDC37 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDC37 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CDC37 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CDC37 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CDC37 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CDC37 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate CDC37 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for CDC37 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CDC37 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CDC37 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 CDC37 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 CDC37 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 CDC37 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.