CDC37

Last updated
CDC37
Protein CDC37 PDB 1us7.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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
View/Edit Human View/Edit Mouse
Cdc37 N terminal kinase binding
Identifiers
SymbolCDC37_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
PDB 1us7 EBI.jpg
complex of hsp90 and p50
Identifiers
SymbolCDC37_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
PDB 1us7 EBI.jpg
complex of hsp90 and p50
Identifiers
SymbolCDC37_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]

Contents

Interactions

CDC37 has been shown to interact with:

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.

Related Research Articles

<span class="mw-page-title-main">Chaperone (protein)</span> Proteins assisting in protein folding

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.

<span class="mw-page-title-main">Hsp90</span> Heat shock proteins with a molecular mass around 90kDa

Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.

<span class="mw-page-title-main">Stress-induced-phosphoprotein 1</span> Protein-coding gene in the species Homo sapiens

Stress-induced-phosphoprotein 1 also Hsp70-Hsp90 organising protein (Hop) is encoded in the human by the STIP1 gene. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Aryl hydrocarbon receptor</span> Vertebrate receptor protein and transcription factor

The aryl hydrocarbon receptor is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originally thought to function primarily as a sensor of xenobiotic chemicals and also as the regulator of enzymes such as cytochrome P450s that metabolize these chemicals. The most notable of these xenobiotic chemicals are aromatic (aryl) hydrocarbons from which the receptor derives its name.

<span class="mw-page-title-main">Cyclin-dependent kinase 4</span> Human protein

Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. CDK4 is a member of the cyclin-dependent kinase family.

<span class="mw-page-title-main">Cyclin-dependent kinase 6</span> Protein-coding gene in the species Homo sapiens

Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point.

<span class="mw-page-title-main">IKK2</span> Protein-coding gene in the species Homo sapiens

IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB gene.

<span class="mw-page-title-main">RELA</span> Protein-coding gene in the species Homo sapiens

Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.

<span class="mw-page-title-main">PRKCB1</span> Protein-coding gene in the species Homo sapiens

Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene.

<span class="mw-page-title-main">Heat shock protein 90kDa alpha (cytosolic), member A1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the HSP90AA1 gene.

<span class="mw-page-title-main">HSPA1B</span> Human gene

Human gene HSPA1B is an intron-less gene which encodes for the heat shock protein HSP70-2, a member of the Hsp70 family of proteins. The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous genes, HSPA1A and HSPA1L. HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the three prime untranslated region, heat shock 70kDa protein 1A, from HSPA1A, and heat shock 70kDa protein 1B, from HSPA1B. A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.

<span class="mw-page-title-main">Heat shock factor protein 1</span> Protein-coding gene in the species Homo sapiens

Heat shock factor protein 1 is a protein that in humans is encoded by the HSF1 gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.

<span class="mw-page-title-main">HSP90B1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene.

<span class="mw-page-title-main">MAPK7</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.

<span class="mw-page-title-main">CASK</span> Protein-coding gene in humans

Peripheral plasma membrane protein CASK is a protein that in humans is encoded by the CASK gene. This gene is also known by several other names: CMG 2, calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. CASK gene mutations are the cause of XL-ID with or without nystagmus and MICPCH, an X-linked neurological disorder.

<span class="mw-page-title-main">HSP90AB1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.

<span class="mw-page-title-main">PTGES3</span> Protein-coding gene in the species Homo sapiens

Prostaglandin E synthase 3 (cytosolic) is an enzyme that in humans is encoded by the PTGES3 gene.

<span class="mw-page-title-main">DNAJB1</span> Protein-coding gene in the species Homo sapiens

DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the DNAJB1 gene.

The chaperone code refers to post-translational modifications of molecular chaperones that control protein folding. Whilst the genetic code specifies how DNA makes proteins, and the histone code regulates histone-DNA interactions, the chaperone code controls how proteins are folded to produce a functional proteome.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000105401 Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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

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