Reviewed, UniProtKB/Swiss-Prot Q16543 (CDC37_HUMAN)

Names and origin

Protein names

Recommended name:
    Hsp90 co-chaperone Cdc37
Alternative name(s):
    Hsp90 chaperone protein kinase-targeting subunit
    p50Cdc37

Gene names

Name:	CDC37
Synonyms:	CDC37A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	378 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. Ref.1
Subunit structure	Forms a complex with Hsp90. Interacts with AR, CDK4, CDK6, EIF2AK1 and RB1. Ref.7 Ref.9 Ref.10
Subcellular location	Cytoplasm.
Post-translational modification	Constitutively sumoylated by UBE2I. Ref.12
Sequence similarities	Belongs to the CDC37 family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Chaperone
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein targeting Ref.1 Traceable author statement. Source: ProtInc regulation of cyclin-dependent protein kinase activity Ref.1 Traceable author statement. Source: ProtInc regulation of interferon-gamma-mediated signaling pathway Inferred from mutant phenotype. Source: MGI regulation of type I interferon-mediated signaling pathway Inferred from mutant phenotype. Source: MGI
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	heat shock protein binding Inferred from physical interaction. Source: UniProtKB unfolded protein binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P11500	2	EBI-295634,EBI-640126	From a different organism.
AKT1	P31749	1	EBI-295634,EBI-296087
AKT2	P31751	1	EBI-295634,EBI-296058
AKT3	Q9Y243	1	EBI-295634,EBI-296115
CDK4	P11802	4	EBI-295634,EBI-295644
CDK6	Q00534	1	EBI-295634,EBI-295663
EIF2AK1	P33279	1	EBI-295634,EBI-640100	From a different organism.
HSP82	P02829	1	EBI-295634,EBI-8659	From a different organism.
NEK6	Q9HC98	1	EBI-295634,EBI-740364
SGK1	O00141	1	EBI-295634,EBI-1042854
SMYD2	Q9NRG4	1	EBI-295634,EBI-1055671

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 378

378

Hsp90 co-chaperone Cdc37

PRO_0000195057

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.15

Modified residue

13

1

Phosphoserine Ref.15

Modified residue

45

1

N6-acetyllysine Ref.16

Modified residue

78

1

N6-acetyllysine Ref.16

Modified residue

154

1

N6-acetyllysine Ref.16

Modified residue

240

1

N6-acetyllysine Ref.16

Modified residue

298

1

Phosphotyrosine Ref.11

Modified residue

330

1

N6-acetyllysine Ref.16

Modified residue

377

1

Phosphoserine Ref.13

Natural variations

Natural variant

360

1

G → E: dbSNP rs280528. Ref.3

VAR_022220

Secondary structure

1

.

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378

Helix Strand Turn

Details...

Helix

149 – 164

16

Helix

168 – 176

9

Helix

177 – 181

5

Helix

184 – 199

16

Helix

203 – 226

24

Helix

230 – 232

3

Helix

234 – 242

9

Helix

246 – 284

39

Helix

294 – 300

7

Helix

317 – 321

5

Beta strand

325 – 327

3

Helix

328 – 338

11

Sequences

	Sequence		Length	Mass (Da)
	Q16543-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 55BFEFFF3C2A5442	FASTA	378	44,468
	10 20 30 40 50 60 MVDYSVWDHI EVSDDEDETH PNIDTASLFR WRHQARVERM EQFQKEKEEL DRGCRECKRK 70 80 90 100 110 120 VAECQRKLKE LEVAEGGKAE LERLQAEAQQ LRKEERSWEQ KLEEMRKKEK SMPWNVDTLS 130 140 150 160 170 180 KDGFSKSMVN TKPEKTEEDS EEVREQKHKT FVEKYEKQIK HFGMLRRWDD SQKYLSDNVH 190 200 210 220 230 240 LVCEETANYL VIWCIDLEVE EKCALMEQVA HQTIVMQFIL ELAKSLKVDP RACFRQFFTK 250 260 270 280 290 300 IKTADRQYME GFNDELEAFK ERVRGRAKLR IEKAMKEYEE EERKKRLGPG GLDPVEVYES 310 320 330 340 350 360 LPEELQKCFD VKDVQMLQDA ISKMDPTDAK YHMQRCIDSG LWVPNSKASE AKEGEEAGPG 370 DPLLEAVPKT GDEKDVSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4." Stepanova L., Leng X., Parker S.B., Harper J.W. Genes Dev. 10:1491-1502(1996) [PubMed: 8666233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]	"Physical interaction of mammalian CDC37 with CDK4." Dai K., Kobayashi R., Beach D. J. Biol. Chem. 271:22030-22034(1996) [PubMed: 8703009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	NIEHS SNPs program Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-360.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Placenta.
[7]	"Interaction between Cdc37 and Cdk4 in human cells." Lamphere L., Fiore F., Xu X., Brizuela L., Keezer S., Sardet C., Draetta G.F., Gyuris J. Oncogene 14:1999-2004(1997) [PubMed: 9150368] [Abstract] Cited for: INTERACTION WITH CDK4 AND CDK6.
[8]	"p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules." Hartson S.D., Irwin A.D., Shao J., Scroggins B.T., Volk L., Huang W., Matts R.L. Biochemistry 39:7631-7644(2000) [PubMed: 10858314] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Hsp90 regulates p50(cdc37) function during the biogenesis of the active conformation of the heme-regulated eIF2 alpha kinase." Shao J., Grammatikakis N., Scroggins B.T., Uma S., Huang W., Chen J.-J., Hartson S.D., Matts R.L. J. Biol. Chem. 276:206-214(2001) [PubMed: 11036079] [Abstract] Cited for: INTERACTION WITH EIF2AK1.
[10]	"Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor." Rao J., Lee P., Benzeno S., Cardozo C., Albertus J., Robins D.M., Caplan A.J. J. Biol. Chem. 276:5814-5820(2001) [PubMed: 11085988] [Abstract] Cited for: INTERACTION WITH AR.
[11]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-298, MASS SPECTROMETRY.
[12]	"Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation." Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R. Nucleic Acids Res. 35:E109-E109(2007) [PubMed: 17709345] [Abstract] Cited for: SUMOYLATION.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY.
[16]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-45; LYS-78; LYS-154; LYS-240 AND LYS-330, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U43077 mRNA. Translation: AAB63979.1.
U63131 mRNA. Translation: AAB04798.1.
AY864824 Genomic DNA. Translation: AAW34362.1.
BT006796 mRNA. Translation: AAP35442.1.
CH471106 Genomic DNA. Translation: EAW84101.1.
BC000083 mRNA. Translation: AAH00083.1.
BC008793 mRNA. Translation: AAH08793.1.

IPI

IPI00013122.

PIR

G02313.

RefSeq

NP_008996.1.

UniGene

Hs.160958

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1US7	X-ray	2.30	B	127-378	[»]
2K5B	NMR	-	B	148-276	[»]
2W0G	X-ray	1.88	A	148-276	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27560N.
DIP-395N.

IntAct

Q16543. 38 interactions.

STRING

Q16543.

PTM databases

PhosphoSite

Q16543.

Proteomic databases

PeptideAtlas

Q16543.

PRIDE

Q16543.

Genome annotation databases

Ensembl

ENST00000222005; ENSP00000222005; ENSG00000105401; Homo sapiens. [Genome view]

GeneID

11140.

KEGG

hsa:11140.

UCSC

uc002mof.1. human.

Organism-specific databases

CTD

11140.

GeneCards

GC19M010362.

H-InvDB

HIX0014745.

HGNC

HGNC:1735. CDC37.

HPA

CAB004214.
HPA003928.

MIM

605065. gene.

PharmGKB

PA142672192.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG715286.

HOVERGEN

Q16543.

InParanoid

Q16543.

OMA

GLWVPNA.

OrthoDB

EOG9Q87H8.

PhylomeDB

Q16543.

Gene expression databases

ArrayExpress

Q16543.

Bgee

Q16543.

CleanEx

HS_CDC37.

Genevestigator

Q16543.

GermOnline

ENSG00000105401. Homo sapiens.

Family and domain databases

InterPro

IPR004918. Cdc37.
IPR013873. Cdc37_C.
IPR013874. Cdc37_Hsp90_bd.
IPR013855. Cdc37_N.
[Graphical view]

PANTHER

PTHR12800. Cdc37. 1 hit.

Pfam

PF08564. CDC37_C. 1 hit.
PF08565. CDC37_M. 1 hit.
PF03234. CDC37_N. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

42344.

SOURCE

Search...

Entry information

Entry name

CDC37_HUMAN

Accession

Primary (citable) accession number: Q16543
Secondary accession number(s): Q53YA2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.