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Protein

60 kDa heat shock protein, mitochondrial

Gene

HSPD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:1346131, PubMed:11422376). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable).1 Publication2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei75ATPCombined sources1 Publication1
Binding sitei440ATP; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
Binding sitei520ATPCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi111 – 115ATPCombined sources1 Publication5

GO - Molecular functioni

  • apolipoprotein A-I binding Source: CAFA
  • apolipoprotein binding Source: CAFA
  • ATPase activity Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • chaperone binding Source: UniProtKB
  • DNA replication origin binding Source: BHF-UCL
  • double-stranded RNA binding Source: MGI
  • enzyme binding Source: CAFA
  • high-density lipoprotein particle binding Source: CAFA
  • lipopolysaccharide binding Source: BHF-UCL
  • p53 binding Source: UniProtKB
  • protein binding involved in protein folding Source: GO_Central
  • RNA binding Source: UniProtKB
  • single-stranded DNA binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: BHF-UCL

GO - Biological processi

  • 'de novo' protein folding Source: BHF-UCL
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • apoptotic mitochondrial changes Source: GO_Central
  • B cell activation Source: BHF-UCL
  • B cell cytokine production Source: BHF-UCL
  • B cell proliferation Source: BHF-UCL
  • chaperone-mediated protein complex assembly Source: BHF-UCL
  • chaperone-mediated protein folding Source: GO_Central
  • interaction with symbiont Source: CAFA
  • isotype switching to IgG isotypes Source: BHF-UCL
  • MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • positive regulation of apoptotic process Source: BHF-UCL
  • positive regulation of interferon-alpha production Source: BHF-UCL
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-10 production Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of macrophage activation Source: BHF-UCL
  • positive regulation of T cell activation Source: BHF-UCL
  • positive regulation of T cell mediated immune response to tumor cell Source: BHF-UCL
  • protein import into mitochondrial intermembrane space Source: GO_Central
  • protein maturation Source: BHF-UCL
  • protein refolding Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: Reactome
  • response to cold Source: AgBase
  • response to unfolded protein Source: BHF-UCL
  • T cell activation Source: MGI
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionChaperone, Hydrolase
Biological processHost-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.
R-HSA-8869496. TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation.

Names & Taxonomyi

Protein namesi
Recommended name:
60 kDa heat shock protein, mitochondrial (EC:3.6.4.9)
Alternative name(s):
60 kDa chaperonin
Chaperonin 60
Short name:
CPN60
Heat shock protein 60
Short name:
HSP-60
Short name:
Hsp60
HuCHA60
Mitochondrial matrix protein P1
P60 lymphocyte protein
Gene namesi
Name:HSPD1
Synonyms:HSP60
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000144381.16.
HGNCiHGNC:5261. HSPD1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 13, autosomal dominant (SPG13)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
See also OMIM:605280
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02674898V → I in SPG13. 1 PublicationCorresponds to variant dbSNP:rs66468541Ensembl.1
Leukodystrophy, hypomyelinating, 4 (HLD4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound mental retardation. Death usually occurs within the first two decades of life.
See also OMIM:612233
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05478529D → G in HLD4; transfection with the mutant protein impairs cell growth that worsens with increasing temperature. 1 PublicationCorresponds to variant dbSNP:rs72466451Ensembl.1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Leukodystrophy, Neurodegeneration

Organism-specific databases

DisGeNETi3329.
MalaCardsiHSPD1.
MIMi605280. phenotype.
612233. phenotype.
OpenTargetsiENSG00000144381.
Orphaneti100994. Autosomal dominant spastic paraplegia type 13.
280288. Pelizaeus-Merzbacher-like disease due to HSPD1 mutation.
PharmGKBiPA29527.

Chemistry databases

ChEMBLiCHEMBL4721.

Polymorphism and mutation databases

BioMutaiHSPD1.
DMDMi129379.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 26Mitochondrion7 PublicationsAdd BLAST26
ChainiPRO_000000502627 – 57360 kDa heat shock protein, mitochondrialAdd BLAST547

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31N6-succinyllysineBy similarity1
Modified residuei67PhosphoserineCombined sources1
Modified residuei70PhosphoserineCombined sources1
Modified residuei75N6-acetyllysineBy similarity1
Modified residuei82N6-acetyllysine; alternateCombined sources1
Modified residuei82N6-succinyllysine; alternateBy similarity1
Modified residuei87N6-acetyllysineBy similarity1
Modified residuei90PhosphotyrosineCombined sources1
Modified residuei91N6-acetyllysineBy similarity1
Modified residuei125N6-acetyllysine; alternateCombined sources1
Modified residuei125N6-succinyllysine; alternateBy similarity1
Modified residuei130N6-acetyllysineCombined sources1
Modified residuei133N6-acetyllysine; alternateBy similarity1
Modified residuei133N6-malonyllysine; alternate1 Publication1
Modified residuei133N6-succinyllysine; alternateBy similarity1
Modified residuei156N6-acetyllysineBy similarity1
Modified residuei191N6-acetyllysine; alternateBy similarity1
Modified residuei191N6-succinyllysine; alternateBy similarity1
Modified residuei202N6-acetyllysine; alternateCombined sources1
Modified residuei202N6-succinyllysine; alternateBy similarity1
Modified residuei205N6-acetyllysine; alternateBy similarity1
Modified residuei205N6-succinyllysine; alternateBy similarity1
Modified residuei218N6-acetyllysine; alternateCombined sources1
Modified residuei218N6-succinyllysine; alternateBy similarity1
Modified residuei236N6-acetyllysine; alternateBy similarity1
Modified residuei236N6-succinyllysine; alternateBy similarity1
Modified residuei249N6-acetyllysineBy similarity1
Modified residuei250N6-acetyllysine; alternateBy similarity1
Modified residuei250N6-succinyllysine; alternateBy similarity1
Modified residuei269N6-acetyllysineCombined sources1
Modified residuei292N6-acetyllysineBy similarity1
Modified residuei301N6-succinyllysineBy similarity1
Modified residuei314N6-acetyllysineBy similarity1
Modified residuei352N6-acetyllysine; alternateCombined sources1
Modified residuei352N6-succinyllysine; alternateBy similarity1
Modified residuei359N6-acetyllysineCombined sources1
Modified residuei389N6-acetyllysineBy similarity1
Modified residuei396N6-acetyllysine; alternateCombined sources1
Modified residuei396N6-succinyllysine; alternateBy similarity1
Modified residuei410PhosphoserineBy similarity1
Modified residuei469N6-acetyllysineCombined sources1
Modified residuei481N6-acetyllysine; alternateBy similarity1
Modified residuei481N6-succinyllysine; alternateBy similarity1
Modified residuei488PhosphoserineCombined sources1
Cross-linki551Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP10809.
MaxQBiP10809.
PaxDbiP10809.
PeptideAtlasiP10809.
PRIDEiP10809.
TopDownProteomicsiP10809-1. [P10809-1]

2D gel databases

DOSAC-COBS-2DPAGEiP10809.
OGPiP10809.
REPRODUCTION-2DPAGEiIPI00784154.
P10809.
SWISS-2DPAGEiP10809.
UCD-2DPAGEiP10809.

PTM databases

iPTMnetiP10809.
PhosphoSitePlusiP10809.
SwissPalmiP10809.

Expressioni

Gene expression databases

BgeeiENSG00000144381.
CleanExiHS_HSPD1.
ExpressionAtlasiP10809. baseline and differential.
GenevisibleiP10809. HS.

Organism-specific databases

HPAiCAB002775.
CAB072816.
HPA001523.
HPA050025.

Interactioni

Subunit structurei

Homoheptamer arranged in a ring structure (PubMed:1346131, PubMed:11422376, PubMed:25918392). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. Interacts with 2 heptameric Hsp10 rings to form the symmetrical football complex (PubMed:25918392). Interacts with HRAS (By similarity). Interacts with ATAD3A (PubMed:22664726). Interacts with ETFBKMT and METTL21B (PubMed:23349634).By similarity6 Publications
(Microbial infection) Interacts with HBV protein X and HTLV-1 protein p40tax (PubMed:15120623, PubMed:1731090).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • apolipoprotein A-I binding Source: CAFA
  • apolipoprotein binding Source: CAFA
  • chaperone binding Source: UniProtKB
  • enzyme binding Source: CAFA
  • p53 binding Source: UniProtKB
  • protein binding involved in protein folding Source: GO_Central
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109561. 289 interactors.
CORUMiP10809.
DIPiDIP-58N.
IntActiP10809. 119 interactors.
MINTiMINT-1162735.
STRINGi9606.ENSP00000340019.

Structurei

Secondary structure

1573
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 32Combined sources6
Helixi34 – 51Combined sources18
Helixi52 – 54Combined sources3
Beta strandi61 – 64Combined sources4
Beta strandi67 – 70Combined sources4
Beta strandi72 – 74Combined sources3
Helixi77 – 83Combined sources7
Helixi89 – 108Combined sources20
Helixi113 – 130Combined sources18
Helixi137 – 158Combined sources22
Helixi165 – 175Combined sources11
Turni176 – 178Combined sources3
Helixi180 – 193Combined sources14
Beta strandi197 – 203Combined sources7
Beta strandi205 – 208Combined sources4
Beta strandi210 – 214Combined sources5
Beta strandi216 – 220Combined sources5
Helixi226 – 228Combined sources3
Beta strandi232 – 235Combined sources4
Beta strandi237 – 249Combined sources13
Helixi254 – 266Combined sources13
Beta strandi271 – 276Combined sources6
Helixi280 – 292Combined sources13
Beta strandi297 – 301Combined sources5
Beta strandi305 – 307Combined sources3
Helixi308 – 320Combined sources13
Beta strandi324 – 326Combined sources3
Beta strandi328 – 330Combined sources3
Helixi339 – 341Combined sources3
Beta strandi344 – 350Combined sources7
Beta strandi355 – 360Combined sources6
Helixi364 – 378Combined sources15
Helixi387 – 396Combined sources10
Turni397 – 399Combined sources3
Beta strandi401 – 406Combined sources6
Helixi411 – 433Combined sources23
Beta strandi436 – 438Combined sources3
Turni439 – 441Combined sources3
Helixi442 – 445Combined sources4
Helixi448 – 452Combined sources5
Helixi459 – 471Combined sources13
Helixi474 – 483Combined sources10
Helixi487 – 496Combined sources10
Beta strandi501 – 504Combined sources4
Turni505 – 508Combined sources4
Beta strandi509 – 512Combined sources4
Helixi513 – 516Combined sources4
Beta strandi519 – 521Combined sources3
Helixi522 – 539Combined sources18
Beta strandi542 – 548Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PJ1X-ray3.15A/B/C/D/E/F/G/H/I/J/K/L/M/N27-556[»]
ProteinModelPortaliP10809.
SMRiP10809.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the chaperonin (HSP60) family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0356. Eukaryota.
COG0459. LUCA.
GeneTreeiENSGT00390000005727.
HOGENOMiHOG000076290.
HOVERGENiHBG001982.
InParanoidiP10809.
KOiK04077.
OMAiTDTDKME.
OrthoDBiEOG091G04JM.
PhylomeDBiP10809.
TreeFamiTF300475.

Family and domain databases

CDDicd03344. GroEL. 1 hit.
Gene3Di1.10.560.10. 2 hits.
3.50.7.10. 1 hit.
HAMAPiMF_00600. CH60. 1 hit.
InterProiView protein in InterPro
IPR018370. Chaperonin_Cpn60_CS.
IPR001844. Chaprnin_Cpn60.
IPR002423. Cpn60/TCP-1.
IPR027409. GroEL-like_apical_dom.
IPR027413. GROEL-like_equatorial.
PfamiView protein in Pfam
PF00118. Cpn60_TCP1. 1 hit.
PRINTSiPR00298. CHAPERONIN60.
SUPFAMiSSF52029. SSF52029. 1 hit.
TIGRFAMsiTIGR02348. GroEL. 1 hit.
PROSITEiView protein in PROSITE
PS00296. CHAPERONINS_CPN60. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10809-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLRLPTVFRQ MRPVSRVLAP HLTRAYAKDV KFGADARALM LQGVDLLADA
60 70 80 90 100
VAVTMGPKGR TVIIEQSWGS PKVTKDGVTV AKSIDLKDKY KNIGAKLVQD
110 120 130 140 150
VANNTNEEAG DGTTTATVLA RSIAKEGFEK ISKGANPVEI RRGVMLAVDA
160 170 180 190 200
VIAELKKQSK PVTTPEEIAQ VATISANGDK EIGNIISDAM KKVGRKGVIT
210 220 230 240 250
VKDGKTLNDE LEIIEGMKFD RGYISPYFIN TSKGQKCEFQ DAYVLLSEKK
260 270 280 290 300
ISSIQSIVPA LEIANAHRKP LVIIAEDVDG EALSTLVLNR LKVGLQVVAV
310 320 330 340 350
KAPGFGDNRK NQLKDMAIAT GGAVFGEEGL TLNLEDVQPH DLGKVGEVIV
360 370 380 390 400
TKDDAMLLKG KGDKAQIEKR IQEIIEQLDV TTSEYEKEKL NERLAKLSDG
410 420 430 440 450
VAVLKVGGTS DVEVNEKKDR VTDALNATRA AVEEGIVLGG GCALLRCIPA
460 470 480 490 500
LDSLTPANED QKIGIEIIKR TLKIPAMTIA KNAGVEGSLI VEKIMQSSSE
510 520 530 540 550
VGYDAMAGDF VNMVEKGIID PTKVVRTALL DAAGVASLLT TAEVVVTEIP
560 570
KEEKDPGMGA MGGMGGGMGG GMF
Length:573
Mass (Da):61,055
Last modified:August 1, 1990 - v2
Checksum:iE51E1BAD9615899C
GO
Isoform 2 (identifier: P10809-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     144-158: VMLAVDAVIAELKKQ → RNVCCHHSVLNFSVL
     159-573: Missing.

Note: No experimental confirmation available.
Show »
Length:158
Mass (Da):17,100
Checksum:i9FC1907D8E2C1ECE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67S → G in AAA36022 (PubMed:1980192).Curated1
Sequence conflicti111D → N in BAG35173 (PubMed:14702039).Curated1
Sequence conflicti177N → S in BAG35173 (PubMed:14702039).Curated1
Sequence conflicti202K → KAS in ABB01006 (Ref. 4) Curated1
Sequence conflicti260A → T in BAG35173 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05478529D → G in HLD4; transfection with the mutant protein impairs cell growth that worsens with increasing temperature. 1 PublicationCorresponds to variant dbSNP:rs72466451Ensembl.1
Natural variantiVAR_02674898V → I in SPG13. 1 PublicationCorresponds to variant dbSNP:rs66468541Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056144144 – 158VMLAV…ELKKQ → RNVCCHHSVLNFSVL in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_056145159 – 573Missing in isoform 2. 1 PublicationAdd BLAST415

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22382 mRNA. Translation: AAA60127.1.
M34664 mRNA. Translation: AAA36022.1.
AJ250915 Genomic DNA. Translation: CAB75426.1.
DQ217936 Genomic DNA. Translation: ABB01006.1.
AK301276 mRNA. Translation: BAH13448.1.
AK312240 mRNA. Translation: BAG35173.1.
AC010746 Genomic DNA. No translation available.
AC020550 Genomic DNA. No translation available.
AC114809 Genomic DNA. No translation available.
BC002676 mRNA. Translation: AAH02676.1.
BC003030 mRNA. Translation: AAH03030.1.
BC067082 mRNA. Translation: AAH67082.1.
BC073746 mRNA. Translation: AAH73746.1.
CCDSiCCDS33357.1. [P10809-1]
PIRiA32800.
RefSeqiNP_002147.2. NM_002156.4. [P10809-1]
NP_955472.1. NM_199440.1. [P10809-1]
UniGeneiHs.595053.
Hs.727543.

Genome annotation databases

EnsembliENST00000345042; ENSP00000340019; ENSG00000144381. [P10809-1]
ENST00000388968; ENSP00000373620; ENSG00000144381. [P10809-1]
GeneIDi3329.
KEGGihsa:3329.
UCSCiuc002uui.4. human. [P10809-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCH60_HUMAN
AccessioniPrimary (citable) accession number: P10809
Secondary accession number(s): B2R5M6
, B7Z712, Q38L19, Q9UCR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: August 1, 1990
Last modified: September 27, 2017
This is version 214 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families