Summary: Cdc37 C terminal domain
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CDC37 Edit Wikipedia article
| Cdc37 N terminal kinase binding | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | CDC37_N | ||||||||
| Pfam | PF03234 | ||||||||
| InterPro | IPR013855 | ||||||||
| SCOPe | 1us7 / SUPFAM | ||||||||
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| Cdc37 Hsp90 binding domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 complex of hsp90 and p50 | |||||||||
| Identifiers | |||||||||
| Symbol | CDC37_M | ||||||||
| Pfam | PF08565 | ||||||||
| InterPro | IPR013874 | ||||||||
| SCOPe | 1us7 / SUPFAM | ||||||||
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| Cdc37 C terminal domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
complex of hsp90 and p50 | |||||||||
| Identifiers | |||||||||
| Symbol | CDC37_C | ||||||||
| Pfam | PF08564 | ||||||||
| InterPro | IPR013873 | ||||||||
| SCOPe | 1us7 / SUPFAM | ||||||||
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Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene.[5][6]
The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces 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, 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:
Domain architecture
CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases.[15] The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain.[16] The function of the C-terminal domain is unclear.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000105401 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019471 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Dai K, Kobayashi R, Beach D (Oct 1996). "Physical interaction of mammalian CDC37 with CDK4". J Biol Chem. 271 (36): 22030–4. doi:10.1074/jbc.271.36.22030. PMID 8703009.
- ^ a b Stepanova L, Leng X, Parker SB, Harper JW (Aug 1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4". Genes Dev. 10 (12): 1491–502. doi:10.1101/gad.10.12.1491. PMID 8666233.
- ^ "Entrez Gene: CDC37 cell division cycle 37 homolog (S. cerevisiae)".
- ^ 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- ^ Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J (1997). "Interaction between Cdc37 and Cdk4 in human cells". Oncogene. 14 (16): 1999–2004. doi:10.1038/sj.onc.1201036. PMID 9150368.
- ^ Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, Prodromou C, Pearl LH (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.
- ^ Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (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". J. Biol. Chem. 273 (32): 20090–5. doi:10.1074/jbc.273.32.20090. PMID 9685350.
- ^ 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 (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- ^ a b Chen G, Cao P, Goeddel DV (2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Mol. Cell. 9 (2): 401–10. doi:10.1016/S1097-2765(02)00450-1. PMID 11864612.
- ^ Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR (2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability". Biochem. J. 370 (Pt 3): 849–57. doi:10.1042/BJ20021813. PMC 1223241. PMID 12489981.
- ^ Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RI, Lindquist S (July 1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction". Genes Dev. 11 (14): 1775–85. doi:10.1101/gad.11.14.1775. PMID 9242486.
- ^ Turnbull EL, Martin IV, Fantes PA (August 2005). "Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90". FEBS J. 272 (16): 4129–40. doi:10.1111/j.1742-4658.2005.04825.x. PMID 16098195.
Further reading
- Dey B, Lightbody JJ, Boschelli F (1997). "CDC37 is required for p60v-src activity in yeast". Mol. Biol. Cell. 7 (9): 1405–17. doi:10.1091/mbc.7.9.1405. PMC 275990. PMID 8885235.
- Lamphere L, Fiore F, Xu X, et al. (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, et al. (1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction". Genes Dev. 11 (14): 1775–85. doi:10.1101/gad.11.14.1775. PMID 9242486.
- Silverstein AM, Grammatikakis N, Cochran BH, et al. (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". J. Biol. Chem. 273 (32): 20090–5. doi:10.1074/jbc.273.32.20090. PMID 9685350.
- Grammatikakis N, Lin JH, Grammatikakis A, et al. (1999). "p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function". Mol. Cell. Biol. 19 (3): 1661–72. PMC 83960. PMID 10022854.
- O'Keeffe B, Fong Y, Chen D, et al. (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". J. Biol. Chem. 275 (1): 279–87. doi:10.1074/jbc.275.1.279. PMID 10617616.
- Hartson SD, Irwin AD, Shao J, et al. (2000). "p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules". Biochemistry. 39 (25): 7631–44. doi:10.1021/bi000315r. PMID 10858314.
- Shao J, Grammatikakis N, Scroggins BT, et al. (2001). "Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase". J. Biol. Chem. 276 (1): 206–14. doi:10.1074/jbc.M007583200. PMID 11036079.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Rao J, Lee P, Benzeno S, et al. (2001). "Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor". J. Biol. Chem. 276 (8): 5814–20. doi:10.1074/jbc.M007385200. PMID 11085988.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Scholz GM, Cartledge K, Hall NE (2001). "Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37". J. Biol. Chem. 276 (33): 30971–9. doi:10.1074/jbc.M103889200. PMID 11413142.
- Chen G, Cao P, Goeddel DV (2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Mol. Cell. 9 (2): 401–10. doi:10.1016/S1097-2765(02)00450-1. PMID 11864612.
- Siligardi G, Panaretou B, Meyer P, et al. (2002). "Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37". J. Biol. Chem. 277 (23): 20151–9. doi:10.1074/jbc.M201287200. PMID 11916974.
- Basso AD, Solit DB, Chiosis G, et al. (2002). "Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function". J. Biol. Chem. 277 (42): 39858–66. doi:10.1074/jbc.M206322200. PMID 12176997.
- Abbas-Terki T, Briand PA, Donzé O, Picard D (2003). "The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically". Biol. Chem. 383 (9): 1335–42. doi:10.1515/BC.2002.152. PMID 12437126.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Boudeau J, Deak M, Lawlor MA, et al. (2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability". Biochem. J. 370 (Pt 3): 849–57. doi:10.1042/BJ20021813. PMC 1223241. PMID 12489981.
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External links
- Human CDC37 genome location and CDC37 gene details page in the UCSC Genome Browser.
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Cdc37 C terminal domain Provide feedback
Cdc37 is a protein required for the activity of numerous eukaryotic protein kinases. This domains corresponds to the C terminal domain whose function is unclear. It is found C terminal to the Hsp90 chaperone (Heat shocked protein 90) binding domain PF08565 and the N terminal kinase binding domain of Cdc37 PF03234 [2].
Literature references
-
Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RI, Lindquist S; , Genes Dev 1997;11:1775-1785.: Cdc37 is a molecular chaperone with specific functions in signal transduction. PUBMED:9242486 EPMC:9242486
-
Turnbull EL, Martin IV, Fantes PA; , FEBS J 2005;272:4129-4140.: Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90. PUBMED:16098195 EPMC:16098195
External database links
| SCOP: | 1us7 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR013873
Cdc37 is a protein required for the activity of numerous eukaryotic protein kinases. This entry corresponds to the C-terminal domain whose function is unclear. It is found C-terminal to the Hsp90 chaperone (heat shock protein 90) binding domain (INTERPRO) and the N-terminal kinase binding domain of Cdc37 (INTERPRO) [PUBMED:16098195].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Alignments
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| Seed (31) |
Full (910) |
Representative proteomes | UniProt (1325) |
NCBI (1485) |
Meta (3) |
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| RP15 (257) |
RP35 (508) |
RP55 (715) |
RP75 (891) |
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| PP/heatmap | 1 | ||||||||
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| Seed (31) |
Full (910) |
Representative proteomes | UniProt (1325) |
NCBI (1485) |
Meta (3) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (257) |
RP35 (508) |
RP55 (715) |
RP75 (891) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_3345 (release 6.5) |
| Previous IDs: | Cdc37; |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Bateman A  , Mistry J , Wood V
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| Number in seed: | 31 |
| Number in full: | 910 |
| Average length of the domain: | 88.00 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 19.41 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model length: | 100 | ||||||||||||
| Family (HMM) version: | 10 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
CDC37_MStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CDC37_C domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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