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Protein

Heat shock cognate 71 kDa protein

Gene

Hspa8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei71ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 15ATPBy similarity4
Nucleotide bindingi202 – 204ATPBy similarity3
Nucleotide bindingi268 – 275ATPBy similarity8
Nucleotide bindingi339 – 342ATPBy similarity4

GO - Molecular functioni

  • A1 adenosine receptor binding Source: RGD
  • ADP binding Source: RGD
  • ATPase activity Source: MGI
  • ATPase activity, coupled Source: RGD
  • ATP binding Source: RGD
  • clathrin-uncoating ATPase activity Source: RGD
  • enzyme binding Source: RGD
  • heat shock protein binding Source: GO_Central
  • misfolded protein binding Source: GO_Central
  • peptide binding Source: RGD
  • prostaglandin binding Source: RGD
  • protein binding involved in protein folding Source: GO_Central
  • RNA binding Source: RGD
  • signaling receptor binding Source: RGD
  • transcription factor binding Source: RGD
  • unfolded protein binding Source: RGD

GO - Biological processi

Keywordsi

Molecular functionChaperone, Repressor
Biological processmRNA processing, mRNA splicing, Stress response, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock cognate 71 kDa protein
Alternative name(s):
Heat shock 70 kDa protein 8
Gene namesi
Name:Hspa8
Synonyms:Hsc70, Hsc73
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621725 Hspa8

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

Cell membrane, Cytoplasm, Membrane, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000782732 – 646Heat shock cognate 71 kDa proteinAdd BLAST645

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei108N6-acetyllysineBy similarity1
Modified residuei153PhosphoserineBy similarity1
Modified residuei246N6-acetyllysineBy similarity1
Modified residuei319N6-acetyllysine; alternateBy similarity1
Modified residuei319N6-succinyllysine; alternateBy similarity1
Modified residuei328N6-acetyllysineBy similarity1
Modified residuei329PhosphoserineBy similarity1
Modified residuei362PhosphoserineBy similarity1
Modified residuei469Omega-N-methylarginineBy similarity1
Modified residuei512N6-acetyllysine; alternateBy similarity1
Modified residuei512N6-succinyllysine; alternateBy similarity1
Cross-linki512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei524N6-acetyllysineBy similarity1
Modified residuei541PhosphoserineBy similarity1
Modified residuei561N6,N6,N6-trimethyllysine; by METTL21A; alternateBy similarity1
Modified residuei561N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei589N6-acetyllysineBy similarity1
Modified residuei597N6-acetyllysineBy similarity1
Modified residuei601N6-acetyllysineBy similarity1

Post-translational modificationi

Acetylated.By similarity
ISGylated.By similarity
Trimethylation at Lys-561 reduces fibrillar SNCA binding.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP63018
PRIDEiP63018

2D gel databases

World-2DPAGEi0004:P63018

PTM databases

iPTMnetiP63018
PhosphoSitePlusiP63018
SwissPalmiP63018

Expressioni

Inductioni

Constitutively synthesized.

Interactioni

Subunit structurei

Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1 (By similarity). Interacts with DNAJC7 (PubMed:10567422). Interacts with DNAJB12 (via J domain). Interacts with DNAJB14 (via J domain). Interacts (via C-terminus) with the E3 ligase STUB1 forming a 210 kDa complex of one STUB1 and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with TRIM5. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with METTL21A. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain). Interacts with MLLT11. Interacts with RNF207. Interacts with DNAJC21. Interacts with DNAJB2. Interacts with TTC1 (via TPR repeats) (By similarity). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with HSF1 (via transactivation domain). Interacts with HOPX, STUB1, HSP40, HSP90, BAG2 and BAG3 (By similarity). Interacts with DNAJC12 (By similarity). Interacts with HSPC138 (By similarity). Interacts with ZMYND10 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi246629, 16 interactors
CORUMiP63018
DIPiDIP-33262N
IntActiP63018, 12 interactors
MINTiP63018
STRINGi10116.ENSRNOP00000058593

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP63018
SMRiP63018
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63018

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 386Nucleotide-binding domain (NBD)By similarityAdd BLAST385
Regioni186 – 377Interaction with BAG1By similarityAdd BLAST192
Regioni394 – 509Substrate-binding domain (SBD)By similarityAdd BLAST116

Domaini

The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.By similarity

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

eggNOGiKOG0101 Eukaryota
COG0443 LUCA
HOVERGENiHBG051845
InParanoidiP63018
KOiK03283
PhylomeDBiP63018

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P63018-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL
60 70 80 90 100
IGDAAKNQVA MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR
110 120 130 140 150
PKVQVEYKGE TKSFYPEEVS SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF
160 170 180 190 200
NDSQRQATKD AGTIAGLNVL RIINEPTAAA IAYGLDKKVG AERNVLIFDL
210 220 230 240 250
GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH FIAEFKRKHK
260 270 280 290 300
KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
310 320 330 340 350
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL
360 370 380 390 400
QDFFNGKELN KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS
410 420 430 440 450
LGIETAGGVM TVLIKRNTTI PTKQTQTFTT YSDNQPGVLI QVYEGERAMT
460 470 480 490 500
KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI DANGILNVSA VDKSTGKENK
510 520 530 540 550
ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN SLESYAFNMK
560 570 580 590 600
ATVEDEKLQG KINDEDKQKI LDKCNEIISW LDKNQTAEKE EFEHQQKELE
610 620 630 640
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
Length:646
Mass (Da):70,871
Last modified:August 1, 1988 - v1
Checksum:i03A27B30E6C076ED
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D4A4S3D4A4S3_RAT
Heat shock cognate 71 kDa protein
Hspa8
645Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00054 Genomic DNA Translation: CAA68265.1
M11942 mRNA Translation: AAA41354.1
BC061547 mRNA Translation: AAH61547.1
BC098914 mRNA Translation: AAH98914.1
PIRiS07197
RefSeqiNP_077327.1, NM_024351.2
UniGeneiRn.120392
Rn.129299
Rn.201298

Genome annotation databases

GeneIDi24468
KEGGirno:24468
UCSCiRGD:621725 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00054 Genomic DNA Translation: CAA68265.1
M11942 mRNA Translation: AAA41354.1
BC061547 mRNA Translation: AAH61547.1
BC098914 mRNA Translation: AAH98914.1
PIRiS07197
RefSeqiNP_077327.1, NM_024351.2
UniGeneiRn.120392
Rn.129299
Rn.201298

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CKRNMR-A385-543[»]
1Q2Gmodel-C385-543[»]
1UD0X-ray3.45A/B/C/D542-646[»]
2V7ZX-ray3.50A/B1-543[»]
7HSCNMR-A385-543[»]
ProteinModelPortaliP63018
SMRiP63018
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246629, 16 interactors
CORUMiP63018
DIPiDIP-33262N
IntActiP63018, 12 interactors
MINTiP63018
STRINGi10116.ENSRNOP00000058593

PTM databases

iPTMnetiP63018
PhosphoSitePlusiP63018
SwissPalmiP63018

2D gel databases

World-2DPAGEi0004:P63018

Proteomic databases

PaxDbiP63018
PRIDEiP63018

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24468
KEGGirno:24468
UCSCiRGD:621725 rat

Organism-specific databases

CTDi3312
RGDi621725 Hspa8

Phylogenomic databases

eggNOGiKOG0101 Eukaryota
COG0443 LUCA
HOVERGENiHBG051845
InParanoidiP63018
KOiK03283
PhylomeDBiP63018

Miscellaneous databases

EvolutionaryTraceiP63018
PROiPR:P63018

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHSP7C_RAT
AccessioniPrimary (citable) accession number: P63018
Secondary accession number(s): P08109
, P12225, Q4FZY7, Q62373, Q62374, Q62375
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: November 7, 2018
This is version 143 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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