CDC37

CDC37
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1US7, 2K5B, 2W0G, 2N5X, 2NCA, 5FWM, 5FWL, 5FWK
Identifiers
Aliases	CDC37 , P50cell division cycle 37, cell division cycle 37, HSP90 cochaperone
External IDs	OMIM: 605065; MGI: 109531; HomoloGene: 38268; GeneCards: CDC37; OMA:CDC37 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.2 Start 10,391,133 bp [1] End 10,420,121 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 A3 Start 21,044,518 bp [2] End 21,061,278 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve apex of heart granulocyte body of uterus left uterine tube upper lobe of left lung left lobe of thyroid gland gastric mucosa right uterine tube canal of the cervix Top expressed in maxillary prominence mandibular prominence right ventricle neural layer of retina somite dentate gyrus of hippocampal formation granule cell epiblast abdominal wall efferent ductule neural tube More reference expression data BioGPS More reference expression data
Gene ontology Molecular function unfolded protein binding Hsp90 protein binding kinase binding chaperone binding protein binding protein kinase binding heat shock protein binding protein kinase regulator activity protein tyrosine kinase activity scaffold protein binding Cellular component extracellular exosome HSP90-CDC37 chaperone complex cytoplasm cytosol chaperone complex Biological process posttranscriptional regulation of gene expression protein targeting protein stabilization regulation of cyclin-dependent protein serine/threonine kinase activity regulation of type I interferon-mediated signaling pathway regulation of interferon-gamma-mediated signaling pathway positive regulation of mitophagy in response to mitochondrial depolarization regulation of protein kinase activity protein folding peptidyl-tyrosine phosphorylation ERBB2 signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11140 12539 Ensembl ENSG00000105401 ENSMUSG00000019471 UniProt Q16543 Q61081 RefSeq (mRNA) NM_007065 NM_016742 NM_001378796 RefSeq (protein) NP_008996 NP_058022 NP_001365725 Location (UCSC) Chr 19: 10.39 – 10.42 Mb Chr 9: 21.04 – 21.06 Mb PubMed search [3] [4]
Wikidata
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Cdc37 N terminal kinase binding
Identifiers
Symbol	CDC37_N
Pfam	PF03234
InterPro	IPR013855
SCOP2	1us7 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Cdc37 Hsp90 binding domain
complex of hsp90 and p50
Identifiers
Symbol	CDC37_M
Pfam	PF08565
InterPro	IPR013874
SCOP2	1us7 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Cdc37 C terminal domain
complex of hsp90 and p50
Identifiers
Symbol	CDC37_C
Pfam	PF08564
InterPro	IPR013873
SCOP2	1us7 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene. ^[5] This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 Co-chaperone ^[6] 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, RAF1, MOK, as well as eIF-2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases. ^[7]

Interactions

CDC37 has been shown to interact with:

• CDK4, ^{[5] [8] [9] [10]}
• HSP90AA1 ^{[11] [12]}
• IKBKG, ^{[13] [14]}
• IKK2, ^[14] and
• STK11. ^[15]

Domain architecture

CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases. ^[16] The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain. ^[17] The function of the C-terminal domain is unclear.

References

1. GRCh38: Ensembl release 89: ENSG00000105401 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019471 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Dai K, Kobayashi R, Beach D (September 1996). "Physical interaction of mammalian CDC37 with CDK4". The Journal of Biological Chemistry. 271 (36): 22030–22034. doi: 10.1074/jbc.271.36.22030 . PMID   8703009.
6. Mollapour M, Neckers L (March 2012). "Post-translational modifications of Hsp90 and their contributions to chaperone regulation". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1823 (3): 648–655. doi:10.1016/j.bbamcr.2011.07.018. PMC   3226900 . PMID   21856339.
7. "Entrez Gene: CDC37 cell division cycle 37 homolog (S. cerevisiae)".
8. Stepanova L, Leng X, Parker SB, Harper JW (June 1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4". Genes & Development. 10 (12): 1491–1502. doi: 10.1101/gad.10.12.1491 . PMID   8666233.
9. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1) 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
10. Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, et al. (April 1997). "Interaction between Cdc37 and Cdk4 in human cells". Oncogene. 14 (16): 1999–2004. doi: 10.1038/sj.onc.1201036 . PMID   9150368.
11. Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, et al. (January 2004). "The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)". Cell. 116 (1): 87–98. doi: 10.1016/S0092-8674(03)01027-4 . PMID   14718169. S2CID   797232.
12. Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (August 1998). "p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site". The Journal of Biological Chemistry. 273 (32): 20090–20095. doi: 10.1074/jbc.273.32.20090 . PMID   9685350.
13. Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID   14743216. S2CID   11683986.
14. Chen G, Cao P, Goeddel DV (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Molecular Cell. 9 (2): 401–410. doi: 10.1016/S1097-2765(02)00450-1 . PMID   11864612.
15. Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR (March 2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability". The Biochemical Journal. 370 (Pt 3): 849–857. doi:10.1042/BJ20021813. PMC   1223241 . PMID   12489981.
16. Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, et al. (July 1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction". Genes & Development. 11 (14): 1775–1785. doi: 10.1101/gad.11.14.1775 . PMID   9242486.
17. Turnbull EL, Martin IV, Fantes PA (August 2005). "Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90". The FEBS Journal. 272 (16): 4129–4140. doi: 10.1111/j.1742-4658.2005.04825.x . PMID   16098195. S2CID   23442218.

Further reading

• Dey B, Lightbody JJ, Boschelli F (September 1996). "CDC37 is required for p60v-src activity in yeast". Molecular Biology of the Cell. 7 (9): 1405–1417. doi:10.1091/mbc.7.9.1405. PMC   275990 . PMID   8885235.
• Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, et al. (April 1997). "Interaction between Cdc37 and Cdk4 in human cells". Oncogene. 14 (16): 1999–2004. doi: 10.1038/sj.onc.1201036 . PMID   9150368.
• Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, et al. (July 1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction". Genes & Development. 11 (14): 1775–1785. doi: 10.1101/gad.11.14.1775 . PMID   9242486.
• Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (August 1998). "p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site". The Journal of Biological Chemistry. 273 (32): 20090–20095. doi: 10.1074/jbc.273.32.20090 . PMID   9685350.
• Grammatikakis N, Lin JH, Grammatikakis A, Tsichlis PN, Cochran BH (March 1999). "p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function". Molecular and Cellular Biology. 19 (3): 1661–1672. doi:10.1128/mcb.19.3.1661. PMC   83960 . PMID   10022854.
• O'Keeffe B, Fong Y, Chen D, Zhou S, Zhou Q (January 2000). "Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription". The Journal of Biological Chemistry. 275 (1): 279–287. doi: 10.1074/jbc.275.1.279 . PMID   10617616.
• Hartson SD, Irwin AD, Shao J, Scroggins BT, Volk L, Huang W, Matts RL (June 2000). "p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules". Biochemistry. 39 (25): 7631–7644. doi:10.1021/bi000315r. PMID   10858314.
• Shao J, Grammatikakis N, Scroggins BT, Uma S, Huang W, Chen JJ, et al. (January 2001). "Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase". The Journal of Biological Chemistry. 276 (1): 206–214. doi: 10.1074/jbc.M007583200 . PMID   11036079.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Rao J, Lee P, Benzeno S, Cardozo C, Albertus J, Robins DM, Caplan AJ (February 2001). "Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor". The Journal of Biological Chemistry. 276 (8): 5814–5820. doi: 10.1074/jbc.M007385200 . PMID   11085988.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–292. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Scholz GM, Cartledge K, Hall NE (August 2001). "Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37". The Journal of Biological Chemistry. 276 (33): 30971–30979. doi: 10.1074/jbc.M103889200 . PMID   11413142.
• Chen G, Cao P, Goeddel DV (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Molecular Cell. 9 (2): 401–410. doi: 10.1016/S1097-2765(02)00450-1 . PMID   11864612.
• Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson DN, Piper PW, et al. (June 2002). "Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37". The Journal of Biological Chemistry. 277 (23): 20151–20159. doi: 10.1074/jbc.M201287200 . PMID   11916974.
• Basso AD, Solit DB, Chiosis G, Giri B, Tsichlis P, Rosen N (October 2002). "Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function". The Journal of Biological Chemistry. 277 (42): 39858–39866. doi: 10.1074/jbc.M206322200 . PMID   12176997.
• Abbas-Terki T, Briand PA, Donzé O, Picard D (September 2002). "The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically". Biological Chemistry. 383 (9): 1335–1342. doi:10.1515/BC.2002.152. PMID   12437126. S2CID   9277739.
• Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR (March 2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability". The Biochemical Journal. 370 (Pt 3): 849–857. doi:10.1042/BJ20021813. PMC   1223241 . PMID   12489981.

External links

• Human CDC37 genome location and CDC37 gene details page in the UCSC Genome Browser .

This article incorporates text from the public domain Pfam and InterPro: IPR013855

This article incorporates text from the public domain Pfam and InterPro: IPR013874

This article incorporates text from the public domain Pfam and InterPro: IPR013873