Hspa8
entrez
15481
canonical
uniprot
P63017
canonical
ensembl
ENSMUSG00000015656
resolver
ensp
ENSMUSP00000015800
resolver
ensp
ENSMUSP00000113722
resolver
enst
ENSMUST00000015800
resolver
enst
ENSMUST00000117557
resolver
genesymbol
Hspa8
resolver
genesymbol_syn
Hsc70
resolver
genesymbol_syn
Hsc73
resolver
uniprot
F7AZ60
resolver
uniprot
P08109
resolver
uniprot
P12225
resolver
uniprot
Q3U6R0
resolver
uniprot
Q3U764
resolver
uniprot
Q3U7D7
resolver
uniprot
Q3U7E2
resolver
uniprot
Q3U9B4
resolver
uniprot
Q3U9G0
resolver
uniprot
Q3UGM0
resolver
uniprot
Q504P4
resolver
uniprot
Q5FWJ6
resolver
uniprot
Q62373
resolver
uniprot
Q62374
resolver
uniprot
Q62375
resolver
uniprot
Q6NZD0
resolver
uniprot_entry
F7AZ60_MOUSE
resolver
uniprot_entry
HSP7C_MOUSE
resolver
uniprot_entry
Q504P4_MOUSE
resolver
uniprot_sec
P08109
resolver
uniprot_sec
P12225
resolver
uniprot_sec
Q3U6R0
resolver
uniprot_sec
Q3U764
resolver
uniprot_sec
Q3U7D7
resolver
uniprot_sec
Q3U7E2
resolver
uniprot_sec
Q3U9B4
resolver
uniprot_sec
Q3U9G0
resolver
uniprot_sec
Q3UGM0
resolver
uniprot_sec
Q5FWJ6
resolver
uniprot_sec
Q62373
resolver
uniprot_sec
Q62374
resolver
uniprot_sec
Q62375
resolver
uniprot_sec
Q6NZD0
resolver
amino_acid_sequence
MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTAAAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEIISWLDKNQTAEKEEFEHQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
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 (PubMed:30718432). 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. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. 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. 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:30718432). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:30718432). 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. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. 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:P11142, ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:30718432}.
uniprot
proteins
mass_dalton
70871
uniprot
proteins
post_translational_modification
PTM: Acetylated. {ECO:0000250|UniProtKB:P11142}.; PTM: ISGylated. {ECO:0000269|PubMed:16139798}.; PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding. {ECO:0000250|UniProtKB:P11142}.
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
10095055
uniprot
proteins
pubmed
15292236
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17233114
uniprot
proteins
pubmed
20060297
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21502331
uniprot
proteins
pubmed
2251119
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
23921388
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
30718432
uniprot
proteins
pubmed
3334718
uniprot
proteins
pubmed
8682318
uniprot
proteins
pubmed
9675148
uniprot
proteins
sequence_length
646
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11142}. Melanosome {ECO:0000250|UniProtKB:P11142}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P11142}. Cell membrane {ECO:0000250|UniProtKB:P11142}. Lysosome membrane {ECO:0000250|UniProtKB:P11142}; Peripheral membrane protein {ECO:0000250|UniProtKB:P11142}; Cytoplasmic side {ECO:0000250|UniProtKB:P11142}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock. {ECO:0000250|UniProtKB:P11142}.
uniprot
proteins