CDC37

{{Short description|Protein-coding gene in humans}} {{Infobox_gene}} {{Infobox protein family | Symbol = CDC37_N | Name = Cdc37 N terminal kinase binding | image = | width = | caption = | Pfam = PF03234 | Pfam_clan = | InterPro = IPR013855 | SMART = | PROSITE = | MEROPS = | SCOP = 1us7 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} {{Infobox protein family | Symbol = CDC37_M | Name = Cdc37 Hsp90 binding domain | image = PDB 1us7 EBI.jpg | width = | caption = complex of hsp90 and p50 | Pfam = PF08565 | Pfam_clan = | InterPro = IPR013874 | SMART = | PROSITE = | MEROPS = | SCOP = 1us7 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} {{Infobox protein family | Symbol = CDC37_C | Name = Cdc37 C terminal domain | image = PDB 1us7 EBI.jpg | width = | caption = complex of hsp90 and p50 | Pfam = PF08564 | Pfam_clan = | InterPro = IPR013873 | SMART = | PROSITE = | MEROPS = | SCOP = 1us7 | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Hsp90 co-chaperone Cdc37''' is a protein that in humans is encoded by the ''CDC37'' gene.<ref name="pmid8703009">{{cite journal | vauthors = Dai K, Kobayashi R, Beach D | title = Physical interaction of mammalian CDC37 with CDK4 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 36 | pages = 22030–22034 | date = September 1996 | pmid = 8703009 | doi = 10.1074/jbc.271.36.22030 | doi-access = free }}</ref> This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 Co-chaperone<ref>{{cite journal | vauthors = Mollapour M, Neckers L | title = Post-translational modifications of Hsp90 and their contributions to chaperone regulation | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1823 | issue = 3 | pages = 648–655 | date = March 2012 | pmid = 21856339 | pmc = 3226900 | doi = 10.1016/j.bbamcr.2011.07.018 }}</ref> 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.<ref name="entrez">{{cite web | title = Entrez Gene: CDC37 cell division cycle 37 homolog (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=11140}}</ref>

== Interactions ==

CDC37 has been shown to interact with: {{div col|colwidth=20em}} * CDK4,<ref name = pmid8703009 /><ref name="pmid8666233">{{cite journal | vauthors = Stepanova L, Leng X, Parker SB, Harper JW | title = Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4 | journal = Genes & Development | volume = 10 | issue = 12 | pages = 1491–1502 | date = June 1996 | pmid = 8666233 | doi = 10.1101/gad.10.12.1491 | doi-access = free }}</ref><ref name = pmid17353931>{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | display-authors = 6 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | article-number = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}</ref><ref name = pmid9150368>{{cite journal | vauthors = Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J | display-authors = 6 | title = Interaction between Cdc37 and Cdk4 in human cells | journal = Oncogene | volume = 14 | issue = 16 | pages = 1999–2004 | date = April 1997 | pmid = 9150368 | doi = 10.1038/sj.onc.1201036 | doi-access = free }}</ref> * HSP90AA1<ref name = pmid14718169>{{cite journal | vauthors = Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, Prodromou C, Pearl LH | display-authors = 6 | title = The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37) | journal = Cell | volume = 116 | issue = 1 | pages = 87–98 | date = January 2004 | pmid = 14718169 | doi = 10.1016/S0092-8674(03)01027-4 | s2cid = 797232 | doi-access = free }}</ref><ref name = pmid9685350>{{cite journal | vauthors = Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB | title = 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 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 32 | pages = 20090–20095 | date = August 1998 | pmid = 9685350 | doi = 10.1074/jbc.273.32.20090 | doi-access = free }}</ref> * IKBKG,<ref name = pmid14743216>{{cite journal | vauthors = Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G | display-authors = 6 | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nature Cell Biology | volume = 6 | issue = 2 | pages = 97–105 | date = February 2004 | pmid = 14743216 | doi = 10.1038/ncb1086 | s2cid = 11683986 }}</ref><ref name = pmid11864612>{{cite journal | vauthors = Chen G, Cao P, Goeddel DV | title = TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90 | journal = Molecular Cell | volume = 9 | issue = 2 | pages = 401–410 | date = February 2002 | pmid = 11864612 | doi = 10.1016/S1097-2765(02)00450-1 | doi-access = free }}</ref> * IKK2,<ref name = pmid11864612/> and * STK11.<ref name = pmid12489981>{{cite journal | vauthors = Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR | title = Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability | journal = The Biochemical Journal | volume = 370 | issue = Pt 3 | pages = 849–857 | date = March 2003 | pmid = 12489981 | pmc = 1223241 | doi = 10.1042/BJ20021813 }}</ref> {{Div col end}}

==Domain architecture==

CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases.<ref name="pmid9242486">{{cite journal | vauthors = Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RI, Lindquist S | display-authors = 6 | title = Cdc37 is a molecular chaperone with specific functions in signal transduction | journal = Genes & Development | volume = 11 | issue = 14 | pages = 1775–1785 | date = July 1997 | pmid = 9242486 | doi = 10.1101/gad.11.14.1775 | doi-access = free }}</ref> The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain.<ref name="pmid16098195">{{cite journal | vauthors = Turnbull EL, Martin IV, Fantes PA | title = Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90 | journal = The FEBS Journal | volume = 272 | issue = 16 | pages = 4129–4140 | date = August 2005 | pmid = 16098195 | doi = 10.1111/j.1742-4658.2005.04825.x | s2cid = 23442218 | doi-access = free }}</ref> The function of the C-terminal domain is unclear.

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Dey B, Lightbody JJ, Boschelli F | title = CDC37 is required for p60v-src activity in yeast | journal = Molecular Biology of the Cell | volume = 7 | issue = 9 | pages = 1405–1417 | date = September 1996 | pmid = 8885235 | pmc = 275990 | doi = 10.1091/mbc.7.9.1405 }} * {{cite journal | vauthors = Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J | display-authors = 6 | title = Interaction between Cdc37 and Cdk4 in human cells | journal = Oncogene | volume = 14 | issue = 16 | pages = 1999–2004 | date = April 1997 | pmid = 9150368 | doi = 10.1038/sj.onc.1201036 | doi-access = free }} * {{cite journal | vauthors = Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RI, Lindquist S | display-authors = 6 | title = Cdc37 is a molecular chaperone with specific functions in signal transduction | journal = Genes & Development | volume = 11 | issue = 14 | pages = 1775–1785 | date = July 1997 | pmid = 9242486 | doi = 10.1101/gad.11.14.1775 | doi-access = free }} * {{cite journal | vauthors = Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB | title = 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 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 32 | pages = 20090–20095 | date = August 1998 | pmid = 9685350 | doi = 10.1074/jbc.273.32.20090 | doi-access = free }} * {{cite journal | vauthors = Grammatikakis N, Lin JH, Grammatikakis A, Tsichlis PN, Cochran BH | title = p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function | journal = Molecular and Cellular Biology | volume = 19 | issue = 3 | pages = 1661–1672 | date = March 1999 | pmid = 10022854 | pmc = 83960 | doi = 10.1128/mcb.19.3.1661 }} * {{cite journal | vauthors = O'Keeffe B, Fong Y, Chen D, Zhou S, Zhou Q | title = 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 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 1 | pages = 279–287 | date = January 2000 | pmid = 10617616 | doi = 10.1074/jbc.275.1.279 | doi-access = free }} * {{cite journal | vauthors = Hartson SD, Irwin AD, Shao J, Scroggins BT, Volk L, Huang W, Matts RL | title = p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules | journal = Biochemistry | volume = 39 | issue = 25 | pages = 7631–7644 | date = June 2000 | pmid = 10858314 | doi = 10.1021/bi000315r }} * {{cite journal | vauthors = Shao J, Grammatikakis N, Scroggins BT, Uma S, Huang W, Chen JJ, Hartson SD, Matts RL | display-authors = 6 | title = Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase | journal = The Journal of Biological Chemistry | volume = 276 | issue = 1 | pages = 206–214 | date = January 2001 | pmid = 11036079 | doi = 10.1074/jbc.M007583200 | doi-access = free }} * {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–1795 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }} * {{cite journal | vauthors = Rao J, Lee P, Benzeno S, Cardozo C, Albertus J, Robins DM, Caplan AJ | title = Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 8 | pages = 5814–5820 | date = February 2001 | pmid = 11085988 | doi = 10.1074/jbc.M007385200 | doi-access = free }} * {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–292 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }} * {{cite journal | vauthors = Scholz GM, Cartledge K, Hall NE | title = Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 33 | pages = 30971–30979 | date = August 2001 | pmid = 11413142 | doi = 10.1074/jbc.M103889200 | doi-access = free }} * {{cite journal | vauthors = Chen G, Cao P, Goeddel DV | title = TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90 | journal = Molecular Cell | volume = 9 | issue = 2 | pages = 401–410 | date = February 2002 | pmid = 11864612 | doi = 10.1016/S1097-2765(02)00450-1 | doi-access = free }} * {{cite journal | vauthors = Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson DN, Piper PW, Pearl LH, Prodromou C | display-authors = 6 | title = Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 23 | pages = 20151–20159 | date = June 2002 | pmid = 11916974 | doi = 10.1074/jbc.M201287200 | doi-access = free }} * {{cite journal | vauthors = Basso AD, Solit DB, Chiosis G, Giri B, Tsichlis P, Rosen N | title = Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39858–39866 | date = October 2002 | pmid = 12176997 | doi = 10.1074/jbc.M206322200 | doi-access = free }} * {{cite journal | vauthors = Abbas-Terki T, Briand PA, Donzé O, Picard D | title = The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically | journal = Biological Chemistry | volume = 383 | issue = 9 | pages = 1335–1342 | date = September 2002 | pmid = 12437126 | doi = 10.1515/BC.2002.152 | s2cid = 9277739 }} * {{cite journal | vauthors = Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR | title = Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability | journal = The Biochemical Journal | volume = 370 | issue = Pt 3 | pages = 849–857 | date = March 2003 | pmid = 12489981 | pmc = 1223241 | doi = 10.1042/BJ20021813 }} {{refend}} {{PDB Gallery|geneid=11140}}

== External links == * {{UCSC gene info|CDC37}}

Category:Co-chaperones