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Protein

Heat shock cognate 71 kDa protein

Gene

HSPA8

Organism
Equus caballus (Horse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone
Biological processmRNA processing, mRNA splicing, Stress response
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
OrganismiEquus caballus (Horse)
Taxonomic identifieri9796 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
Proteomesi
  • UP000002281 Componenti: Unplaced

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_00002860462 – 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; in vitroBy similarity1
Modified residuei561N6,N6-dimethyllysineBy 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

PaxDbiA2Q0Z1.
PeptideAtlasiA2Q0Z1.
PRIDEiA2Q0Z1.

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. Interacts with DNAJC7. 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). Interacts with SGTA (via TPR repeats). Interacts with HSF1 (via transactivation domain). Interacts with HOPX, STUB1, HSP40, HSP901, BAG2 and BAG3.By similarity

Protein-protein interaction databases

STRINGi9796.ENSECAP00000011500.

Structurei

3D structure databases

ProteinModelPortaliA2Q0Z1.
SMRiA2Q0Z1.
ModBaseiSearch...
MobiDBiSearch...

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.
HOGENOMiHOG000228135.
HOVERGENiHBG051845.
InParanoidiA2Q0Z1.
KOiK03283.
OMAiAYTKNQD.

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.
IPR029047. HSP70_peptide-bd.
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.

A2Q0Z1-1 [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 LDKCNEIINW LDKNQTAEKE EFEHQQKELE
610 620 630 640
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
Length:646
Mass (Da):70,898
Last modified:March 6, 2007 - v1
Checksum:i9AA27B210730670C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB292109 mRNA. Translation: BAF46109.1.
RefSeqiNP_001075247.1. NM_001081778.2.
UniGeneiEca.12976.
Eca.19986.

Genome annotation databases

GeneIDi100009679.
KEGGiecb:100009679.

Similar proteinsi

Entry informationi

Entry nameiHSP7C_HORSE
AccessioniPrimary (citable) accession number: A2Q0Z1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: March 6, 2007
Last modified: August 30, 2017
This is version 86 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families