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1  structure 236  species 0  interactions 299  sequences 10  architectures

Family: CDC37_C (PF08564)

Summary: Cdc37 C terminal domain

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This is the Wikipedia entry entitled "CDC37". More...

CDC37 Edit Wikipedia article

Cell division cycle 37

PDB rendering based on 1us7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CDC37; P50CDC37
External IDs OMIM605065 MGI109531 HomoloGene38268 ChEMBL: 1795123 GeneCards: CDC37 Gene
RNA expression pattern
PBB GE CDC37 209953 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 11140 12539
Ensembl ENSG00000105401 ENSMUSG00000019471
UniProt Q16543 Q61081
RefSeq (mRNA) NM_007065 NM_016742
RefSeq (protein) NP_008996 NP_058022
Location (UCSC) Chr 19:
10.5 – 10.53 Mb
Chr 9:
21.14 – 21.15 Mb
PubMed search [1] [2]
Cdc37 N terminal kinase binding
Identifiers
Symbol CDC37_N
Pfam PF03234
InterPro IPR013855
SCOP 1us7
SUPERFAMILY 1us7
Cdc37 Hsp90 binding domain
PDB 1us7 EBI.jpg
complex of hsp90 and p50
Identifiers
Symbol CDC37_M
Pfam PF08565
InterPro IPR013874
SCOP 1us7
SUPERFAMILY 1us7
Cdc37 C terminal domain
PDB 1us7 EBI.jpg
complex of hsp90 and p50
Identifiers
Symbol CDC37_C
Pfam PF08564
InterPro IPR013873
SCOP 1us7
SUPERFAMILY 1us7

Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene.[1][2]

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.[3]

Interactions[edit]

CDC37 has been shown to interact with:

Domain architecture[edit]

CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases.[11] The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain.[12] The function of the C-terminal domain is unclear.

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ "Entrez Gene: CDC37 cell division cycle 37 homolog (S. cerevisiae)". 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. PMID 14718169. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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[edit]

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

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

  1. 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

  2. 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

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

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Alignments

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(31)
Full
(299)
Representative proteomes NCBI
(289)
Meta
(3)
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(59)
RP35
(99)
RP55
(155)
RP75
(188)
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  Seed
(31)
Full
(299)
Representative proteomes NCBI
(289)
Meta
(3)
RP15
(59)
RP35
(99)
RP55
(155)
RP75
(188)
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  Seed
(31)
Full
(299)
Representative proteomes NCBI
(289)
Meta
(3)
RP15
(59)
RP35
(99)
RP55
(155)
RP75
(188)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed 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 View help on the curation process

Seed source: Pfam-B_3345 (release 6.5)
Previous IDs: Cdc37;
Type: Domain
Author: Bateman A, Mistry J, Wood V
Number in seed: 31
Number in full: 299
Average length of the domain: 91.80 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 21.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 21.0 22.1
Noise cut-off 20.7 20.5
Model length: 100
Family (HMM) version: 5
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Species distribution

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Structures

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 1 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 seqence.

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