Hspa5
entrez
14828
canonical
uniprot
P20029
canonical
ensembl
ENSMUSG00000026864
resolver
ensp
ENSMUSP00000028222
resolver
ensp
ENSMUSP00000097747
resolver
enst
ENSMUST00000028222
resolver
enst
ENSMUST00000100171
resolver
genesymbol
Hspa5
resolver
genesymbol_syn
Grp78
resolver
uniprot
O35642
resolver
uniprot
Q3U7T8
resolver
uniprot
Q3UFF2
resolver
uniprot
Q61630
resolver
uniprot_entry
BIP_MOUSE
resolver
uniprot_entry
Q3U7T8_MOUSE
resolver
uniprot_sec
O35642
resolver
uniprot_sec
Q3UFF2
resolver
uniprot_sec
Q61630
resolver
activity_regulation
ACTIVITY REGULATION: The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP. Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P11021}.
uniprot
proteins
amino_acid_sequence
MMKFTVVAAALLLLGAVRAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNRITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVVEKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQRQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNGVFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALSSQHQARIEIESFFEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIVLVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVCPLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLGTFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIERMVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEEKIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSGGPPPTGEEDTSEKDEL
uniprot
proteins
ec_number
3.6.4.10
uniprot
proteins
function
FUNCTION: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:12411443, PubMed:12475965). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (PubMed:12411443). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:10854322). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Also binds and inactivates EIF2AK3/PERK in unstressed cells (PubMed:10854322). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerization and subsequent activation (PubMed:10854322). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (By similarity). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P11021, ECO:0000269|PubMed:12411443, ECO:0000269|PubMed:12475965}.
uniprot
proteins
mass_dalton
72422
uniprot
proteins
post_translational_modification
PTM: In unstressed cells, AMPylation at Thr-519 by FICD inactivates the chaperome activity: AMPylated form is locked in a relatively inert state and only weakly stimulated by J domain-containing proteins. In response to endoplasmic reticulum stress, de-AMPylation by the same protein, FICD, restores the chaperone activity. {ECO:0000250|UniProtKB:G3I8R9}.
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
10854322
uniprot
proteins
pubmed
11836248
uniprot
proteins
pubmed
12065409
uniprot
proteins
pubmed
12411443
uniprot
proteins
pubmed
12475965
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16800626
uniprot
proteins
pubmed
16931514
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
20484814
uniprot
proteins
pubmed
20945367
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21992152
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
23921388
uniprot
proteins
pubmed
25009997
uniprot
proteins
pubmed
2559088
uniprot
proteins
pubmed
2583523
uniprot
proteins
pubmed
27159390
uniprot
proteins
pubmed
2895472
uniprot
proteins
pubmed
33863978
uniprot
proteins
pubmed
7523108
uniprot
proteins
pubmed
7607546
uniprot
proteins
pubmed
8645260
uniprot
proteins
sequence_length
655
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-ProRule:PRU10138, ECO:0000269|PubMed:21992152}. Melanosome {ECO:0000250|UniProtKB:P11021}. Cytoplasm {ECO:0000269|PubMed:21992152}. Cell surface. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (By similarity). Localizes to the cell surface in epithelial cells; high levels of free iron promotes cell surface localization (By similarity). {ECO:0000250|UniProtKB:P11021}.
uniprot
proteins