HSPA8
entrez
3312
canonical
uniprot
P11142
canonical
ensembl
ENSG00000109971
resolver
ensp
ENSP00000404372
resolver
ensp
ENSP00000432083
resolver
ensp
ENSP00000547033
resolver
genesymbol
HEL-S-72p
resolver
genesymbol
HSPA8
resolver
genesymbol_syn
HEL-33
resolver
genesymbol_syn
HSC70
resolver
genesymbol_syn
HSP73
resolver
genesymbol_syn
HSPA10
resolver
genesymbol_syn
HSPA8
resolver
hgnc
HGNC:5241
resolver
uniprot
Q53HF2
resolver
uniprot
Q9H3R6
resolver
uniprot
V9HW22
resolver
uniprot_entry
HSP7C_HUMAN
resolver
uniprot_entry
Q53HF2_HUMAN
resolver
uniprot_entry
V9HW22_HUMAN
resolver
uniprot_sec
Q9H3R6
resolver
amino_acid_sequence
MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTAAAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEIINWLDKNQTAEKEEFEHQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
uniprot
proteins
ec_number
3.6.4.10
uniprot
proteins
function
FUNCTION: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. 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 (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). 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 (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). 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 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). 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 by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}.
uniprot
proteins
mass_dalton
70898
uniprot
proteins
mutagenesis
MUTAGEN 561; /note="K->R: Complete loss of in vitro methylation by METTL21A."; /evidence="ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:23921388
uniprot
proteins
post_translational_modification
PTM: Acetylated. {ECO:0000269|Ref.5, ECO:0000269|Ref.6}.; PTM: ISGylated. {ECO:0000269|PubMed:16139798, ECO:0000269|PubMed:16815975}.; PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding.
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
10722728
uniprot
proteins
pubmed
11093761
uniprot
proteins
pubmed
11147964
uniprot
proteins
pubmed
11276205
uniprot
proteins
pubmed
11559757
uniprot
proteins
pubmed
12526792
uniprot
proteins
pubmed
1286667
uniprot
proteins
pubmed
14532270
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15708368
uniprot
proteins
pubmed
1586970
uniprot
proteins
pubmed
15894275
uniprot
proteins
pubmed
15936278
uniprot
proteins
pubmed
15963462
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16815975
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
17182002
uniprot
proteins
pubmed
17289661
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17785435
uniprot
proteins
pubmed
17947705
uniprot
proteins
pubmed
18320024
uniprot
proteins
pubmed
19131338
uniprot
proteins
pubmed
19256508
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19586912
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20053985
uniprot
proteins
pubmed
20060297
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20176811
uniprot
proteins
pubmed
21148293
uniprot
proteins
pubmed
21150129
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21526763
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23018488
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23349634
uniprot
proteins
pubmed
23865999
uniprot
proteins
pubmed
23921388
uniprot
proteins
pubmed
23973223
uniprot
proteins
pubmed
23990462
uniprot
proteins
pubmed
24121476
uniprot
proteins
pubmed
24122553
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24270810
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24318877
uniprot
proteins
pubmed
24732912
uniprot
proteins
pubmed
24880125
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25281747
uniprot
proteins
pubmed
25760597
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26775844
uniprot
proteins
pubmed
26865365
uniprot
proteins
pubmed
27346687
uniprot
proteins
pubmed
27474739
uniprot
proteins
pubmed
27708256
uniprot
proteins
pubmed
27916661
uniprot
proteins
pubmed
2799391
uniprot
proteins
pubmed
28934328
uniprot
proteins
pubmed
29601588
uniprot
proteins
pubmed
3037489
uniprot
proteins
pubmed
31748398
uniprot
proteins
pubmed
32671205
uniprot
proteins
pubmed
33857403
uniprot
proteins
pubmed
35044787
uniprot
proteins
pubmed
36586411
uniprot
proteins
pubmed
8713105
uniprot
proteins
pubmed
9305631
uniprot
proteins
pubmed
9499401
uniprot
proteins
pubmed
9679980
uniprot
proteins
sequence_length
646
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17289661}. Melanosome {ECO:0000269|PubMed:17081065}. Nucleus, nucleolus {ECO:0000269|PubMed:1586970}. Cell membrane. Lysosome membrane {ECO:0000269|PubMed:11559757}; Peripheral membrane protein {ECO:0000269|PubMed:11559757}; Cytoplasmic side {ECO:0000269|PubMed:11559757}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs (PubMed:17289661). Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock (PubMed:1586970). {ECO:0000269|PubMed:1586970, ECO:0000269|PubMed:17289661}.
uniprot
proteins