Summary: Cdc37 Hsp90 binding domain
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CDC37 Edit Wikipedia article
|, P50cell division cycle 37|
|RNA expression pattern|
|View/Edit Human||View/Edit Mouse|
|Cdc37 N terminal kinase binding|
|Cdc37 Hsp90 binding domain|
complex of hsp90 and p50
|Cdc37 C terminal domain|
complex of hsp90 and p50
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.
CDC37 has been shown to interact with:
CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases. The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain. The function of the C-terminal domain is unclear.
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- 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.
- 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 . 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.
- 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 . 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.
- 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 . 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 . 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 . 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 . 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 . 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 . PMID 12489981.
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 Hsp90 binding domain Provide feedback
Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This domains corresponds to the Hsp90 chaperone (Heat shocked protein 90) binding domain of Cdc37 . It is found between the N terminal Cdc37 domain PF03234 which is predominantly involved in kinase binding, and the C terminal domain of Cdc37 PF08564 whose function is unclear.
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
This tab holds annotation information from the InterPro database.
InterPro entry IPR013874
Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This entry corresponds to the Hsp90 chaperone (heat shock protein 90) binding domain of Cdc37 [PUBMED:16098195]. It is found between the N-terminal Cdc37 domain (INTERPRO), which is predominantly involved in kinase binding, and the C-terminal domain of Cdc37 (INTERPRO) whose function is unclear.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
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.
Note: You can also download the data file for the tree.
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.
|Seed source:||Pfam-B_3345 (release 6.5)|
|Author:||Bateman A, Mistry J, Wood V|
|Number in seed:||58|
|Number in full:||541|
|Average length of the domain:||112.80 aa|
|Average identity of full alignment:||31 %|
|Average coverage of the sequence by the domain:||25.45 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||9|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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_M domain has been found. There are 3 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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