Hsp90 co-chaperone Cdc37 (CDC37)
The protein contains 378 amino acids for an estimated molecular weight of 44468 Da.
Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity (PubMed:8666233). Inhibits HSP90AA1 ATPase activity (PubMed:23569206). (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs280528 |
Biological Process
ERBB2 signaling pathway
Positive regulation of mitophagy in response to mitochondrial depolarization
Posttranscriptional regulation of gene expression
Protein folding
Protein stabilization
Protein targeting
Regulation of cyclin-dependent protein serine/threonine kinase activity
Regulation of interferon-gamma-mediated signaling pathway
Regulation of necroptotic process
Regulation of type I interferon-mediated signaling pathway
The reference OMIM entry for this protein is 605065
Cell division cycle 37, s. cerevisiae, homolog of; cdc37
CLONING
Cyclin-dependent kinase-4 (CDK4; 123829) is a cyclin D-dependent kinase that controls progression through G1 phase of the mammalian cell cycle. To identify proteins involved in CDK4 regulation, Dai et al. (1996) analyzed CDK4 complexes from various cells by immunoprecipitation. Two proteins coimmunoprecipitated with CDK4, one with a molecular mass of 85 kD, which was found to be HSP90 (see 140571), and the other with a molecular mass of 44 kD. Dai et al. (1996) identified the second protein as the human homolog of yeast CDC37. Human CDC37 contains 378 amino acids and shares 45% and 25% amino acid identity with Drosophila and S. cerevisiae CDC37, respectively. Mutations in yeast CDC37 cause cell cycle arrest in G1 phase, and yeast CDC37 is required for the association of CDC28 and cyclin and for the activation of CDC28 (Reed, 1980). Stepanova et al. (1996) independently cloned and characterized human and mouse CDC37 by using sequences from partial cdc37-like chicken cDNA to amplify and screen various human and mouse cDNA libraries. The intracellular distribution of CDC37 was largely cytoplasmic, and the protein appeared to colocalize with cytoplasmic HSP90. CDC37 was expressed in the same tissues during development as D-type cyclins, such as proliferating zones of small intestine and stomach.GENE FUNCTION
In in vitro assays, Stepanova et al. (1996) showed that CDC37 associated most efficiently with CDK4, less with CDK6 (603368) and CDK7 (601955), but not with CDK2 or CDK3. They determined that CDC37, CDK4, and HSP90 form a high molecular weight complex. The interactions between CDK4 and CDC37 and those between CDK4 and D-type cyclins were found to be mutually exclusive. Loss of association of CDC37 and CDK4 by pharmacologic disruption of HSP90 function led to reduced stability of newly synthesized CDK4. Stepanova et al. (1996) concluded that CDC37 and HSP90 are important for CDK4 stability and play a positive role in cell cycle progression. Chen et al. (2002) identified CDC37 and HSP90 as 2 additional components of the I-kappa-B kinase (IKK) complex. This complex also contains 2 catalytic subunits, IKK-alpha (600664) and IKK-beta (603258), and a regulatory subunit, NEMO (300248). Vaughan et al. (2008) stated that CDC37 is phosphorylated on ser13, probably by casein kinase II (see 115440), and that absence of this phosphorylation severely compromises CDC37 function. They showed that ser13 was phosphorylated in vivo in uncomplexed CDC37, in CDC37 in a binary complex with CDK4, and in CDC37 in a ternary complex with CDK4 and HSP90. Ser13 in the CDC37-CDK4-HSP90 complex was resistant to nonspecific phosphatases, but it was efficiently dephosphorylated by protein phosphatase-5 (PP5, or PPP5C; 600658), which did not dephosphorylate uncomplexed CDC37. CDC37 and PP5 associated in HSP90 complexes in yeast and in human tumor cells, and PP5 regulated phosphorylation of ser13 of CDC37 in vivo, directly affecting activation of protein kinases by CDC37-HSP90. Vaughan et al. (2008) proposed that a cyclic regulatory mechanism reverses constitutive CDC37 phosphorylation when CDC37 is engaged in HSP90 complexes. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605065 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed