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Protein

Heat shock cognate 71 kDa protein

Gene

Hspa8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • C3HC4-type RING finger domain binding Source: RGD
  • cadherin binding Source: RGD
  • clathrin-uncoating ATPase activity Source: RGD
  • enzyme binding Source: RGD
  • G-protein coupled receptor binding Source: RGD
  • heat shock protein binding Source: RGD
  • MHC class II protein complex binding Source: RGD
  • peptide binding Source: RGD
  • phosphatidylserine binding Source: RGD
  • prostaglandin binding Source: RGD
  • receptor binding Source: RGD
  • RNA binding Source: RGD
  • transcription factor binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD
  • unfolded protein binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • ATP metabolic process Source: RGD
  • axo-dendritic transport Source: RGD
  • cellular protein complex disassembly Source: MGI
  • cellular response to cadmium ion Source: RGD
  • cellular response to heat Source: RGD
  • cerebellum development Source: RGD
  • chaperone-mediated autophagy Source: ParkinsonsUK-UCL
  • chaperone-mediated autophagy translocation complex disassembly Source: ParkinsonsUK-UCL
  • chaperone-mediated protein folding Source: RGD
  • chaperone mediated protein folding requiring cofactor Source: RGD
  • chaperone-mediated protein transport involved in chaperone-mediated autophagy Source: MGI
  • clathrin coat disassembly Source: RGD
  • estrous cycle Source: RGD
  • forebrain development Source: RGD
  • G1/S transition of mitotic cell cycle Source: RGD
  • kidney development Source: RGD
  • late endosomal microautophagy Source: RGD
  • modulation by host of viral process Source: RGD
  • mRNA processing Source: UniProtKB-KW
  • negative regulation of cardiac muscle cell apoptotic process Source: RGD
  • negative regulation of hydrogen peroxide-induced cell death Source: RGD
  • negative regulation of supramolecular fiber organization Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation by host of viral genome replication Source: RGD
  • positive regulation of catalytic activity Source: RGD
  • positive regulation of gene expression Source: RGD
  • positive regulation of lysosomal membrane permeability Source: RGD
  • positive regulation of mRNA splicing, via spliceosome Source: RGD
  • positive regulation of phagocytosis Source: RGD
  • positive regulation of protein refolding Source: RGD
  • positive regulation of proteolysis Source: RGD
  • positive regulation of T cell mediated cytotoxicity Source: RGD
  • protein autophosphorylation Source: RGD
  • protein folding Source: RGD
  • protein import into nucleus Source: RGD
  • protein refolding Source: ParkinsonsUK-UCL
  • protein targeting to lysosome involved in chaperone-mediated autophagy Source: RGD
  • protein transmembrane import into intracellular organelle Source: RGD
  • regulation of cell cycle Source: RGD
  • regulation of protein complex stability Source: ParkinsonsUK-UCL
  • regulation of protein stability Source: RGD
  • response to activity Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to heat Source: RGD
  • response to nickel cation Source: RGD
  • response to odorant Source: RGD
  • response to progesterone Source: RGD
  • response to starvation Source: RGD
  • RNA splicing Source: UniProtKB-KW
  • sensory perception of smell Source: RGD
  • skeletal muscle tissue development Source: RGD
  • slow axonal transport Source: RGD
  • synaptic vesicle uncoating Source: SynGO
  • transcription, DNA-templated Source: UniProtKB-KW

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.

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).By similarity2 Publications

GO - Molecular functioni

  • A1 adenosine receptor binding Source: RGD
  • C3HC4-type RING finger domain binding Source: RGD
  • cadherin binding Source: RGD
  • enzyme binding Source: RGD
  • G-protein coupled receptor binding Source: RGD
  • heat shock protein binding Source: RGD
  • MHC class II protein complex binding Source: RGD
  • receptor binding Source: RGD
  • transcription factor binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD
  • unfolded protein binding Source: RGD

Protein-protein interaction databases

BioGridi246629. 16 interactors.
CORUMiP63018.
DIPiDIP-33262N.
IntActiP63018. 12 interactors.
MINTiMINT-2514077.
STRINGi10116.ENSRNOP00000058593.

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 10Combined sources5
Beta strandi13 – 22Combined sources10
Beta strandi25 – 28Combined sources4
Beta strandi32 – 34Combined sources3
Beta strandi41 – 44Combined sources4
Beta strandi49 – 52Combined sources4
Helixi53 – 58Combined sources6
Turni59 – 61Combined sources3
Beta strandi66 – 68Combined sources3
Turni71 – 75Combined sources5
Helixi81 – 86Combined sources6
Beta strandi91 – 97Combined sources7
Beta strandi100 – 105Combined sources6
Beta strandi112 – 114Combined sources3
Helixi116 – 135Combined sources20
Beta strandi141 – 146Combined sources6
Helixi152 – 165Combined sources14
Beta strandi168 – 174Combined sources7
Helixi175 – 182Combined sources8
Turni183 – 186Combined sources4
Beta strandi193 – 200Combined sources8
Beta strandi205 – 213Combined sources9
Beta strandi216 – 223Combined sources8
Helixi230 – 249Combined sources20
Helixi257 – 276Combined sources20
Beta strandi278 – 288Combined sources11
Beta strandi291 – 298Combined sources8
Helixi299 – 305Combined sources7
Helixi307 – 312Combined sources6
Helixi314 – 323Combined sources10
Helixi328 – 330Combined sources3
Beta strandi332 – 338Combined sources7
Helixi339 – 342Combined sources4
Helixi344 – 353Combined sources10
Turni354 – 356Combined sources3
Turni365 – 367Combined sources3
Helixi368 – 380Combined sources13
Beta strandi388 – 391Combined sources4
Beta strandi396 – 399Combined sources4
Beta strandi401 – 405Combined sources5
Turni406 – 408Combined sources3
Beta strandi409 – 411Combined sources3
Beta strandi418 – 429Combined sources12
Beta strandi431 – 434Combined sources4
Beta strandi438 – 445Combined sources8
Beta strandi447 – 450Combined sources4
Beta strandi452 – 461Combined sources10
Beta strandi468 – 470Combined sources3
Beta strandi472 – 481Combined sources10
Turni482 – 484Combined sources3
Beta strandi485 – 492Combined sources8
Turni493 – 496Combined sources4
Beta strandi497 – 503Combined sources7
Helixi511 – 518Combined sources8
Turni519 – 521Combined sources3
Helixi522 – 527Combined sources6
Turni532 – 534Combined sources3
Beta strandi537 – 541Combined sources5
Helixi542 – 553Combined sources12
Helixi556 – 558Combined sources3
Turni559 – 561Combined sources3
Helixi564 – 595Combined sources32
Helixi597 – 610Combined sources14

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...

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.
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.

Sequencei

Sequence statusi: Complete.

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

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

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

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 22, 2017
This is version 137 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families