HSPA5
entrez
3309
canonical
uniprot
P11021
canonical
ensembl
ENSG00000044574
resolver
ensp
ENSP00000324173
resolver
enst
ENST00000324460
resolver
genesymbol
HEL-S-89n
resolver
genesymbol
HSPA5
resolver
genesymbol_syn
GRP78
resolver
hgnc
HGNC:5238
resolver
uniprot
B0QZ61
resolver
uniprot
Q2EF78
resolver
uniprot
Q9NPF1
resolver
uniprot
Q9UK02
resolver
uniprot
V9HWB4
resolver
uniprot_entry
BIP_HUMAN
resolver
uniprot_entry
V9HWB4_HUMAN
resolver
uniprot_sec
B0QZ61
resolver
uniprot_sec
Q2EF78
resolver
uniprot_sec
Q9NPF1
resolver
uniprot_sec
Q9UK02
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. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (PubMed:26655470). 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 (PubMed:26655470). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP (By similarity). 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:0000269|PubMed:26655470, ECO:0000303|PubMed:28286085}.
uniprot
proteins
amino_acid_sequence
MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNRITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVVEKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQRQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNGVFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALSSQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIVLVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVCPLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLGTFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIERMVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEEKIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL
uniprot
proteins
disease_involvement
DISEASE: Note=Autoantigen in rheumatoid arthritis. {ECO:0000269|PubMed:11160188}.
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:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). 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 (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:11907036, PubMed:1550958, PubMed:19538957, PubMed:36739529). 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:11907036). 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:11907036). 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 (PubMed:26045166). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P20029, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:1550958, ECO:0000269|PubMed:19538957, ECO:0000269|PubMed:2294010, ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:26045166, ECO:0000269|PubMed:28332555, ECO:0000269|PubMed:29719251, ECO:0000269|PubMed:36739529}.; FUNCTION: (Microbial infection) Plays an important role in viral binding to the host cell membrane and entry for several flaviruses such as Dengue virus, Zika virus and Japanese encephalitis virus (PubMed:15098107, PubMed:28053106, PubMed:33432092). Acts as a component of the cellular receptor for Dengue virus serotype 2/DENV-2 on human liver cells (PubMed:15098107). {ECO:0000269|PubMed:15098107, ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}.; FUNCTION: (Microbial infection) Acts as a receptor for CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:20484814, PubMed:24355926, PubMed:32487760). Acts as a receptor for R.delemar CotH3 in nasal epithelial cells, which may be an early step in rhinoorbital/cerebral mucormycosis (RCM) disease progression (PubMed:32487760). {ECO:0000269|PubMed:20484814, ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:32487760}.
uniprot
proteins
mass_dalton
72333
uniprot
proteins
mutagenesis
MUTAGEN 229; /note="T->A: Impaired ATPase activity."; /evidence="ECO:0000269|PubMed:26655470"; MUTAGEN 492; /note="R->E: Significantly reduced binding to ZIKVE and NS1 proteins."; /evidence="ECO:0000269|PubMed:38710792"; MUTAGEN 518; /note="T->A: Significantly reduced binding to ZIKVE and NS1 proteins."; /evidence="ECO:0000269|PubMed:38710792"; MUTAGEN 585; /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: AMPylated by FICD (PubMed:25601083). In unstressed cells, AMPylation at Thr-518 by FICD inactivates the chaperome activity: AMPylated form is locked in a relatively inert state and only weakly stimulated by J domain-containing proteins (By similarity). In response to endoplasmic reticulum stress, de-AMPylation by the same protein, FICD, restores the chaperone activity (By similarity). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000269|PubMed:25601083}.
uniprot
proteins
protein_family
Heat shock protein 70 family
uniprot
proteins
pubmed
11160188
uniprot
proteins
pubmed
11907036
uniprot
proteins
pubmed
12411443
uniprot
proteins
pubmed
12475965
uniprot
proteins
pubmed
12643545
uniprot
proteins
pubmed
12699405
uniprot
proteins
pubmed
1480470
uniprot
proteins
pubmed
15098107
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1550958
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
18264092
uniprot
proteins
pubmed
18502753
uniprot
proteins
pubmed
18621045
uniprot
proteins
pubmed
19538957
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20072699
uniprot
proteins
pubmed
20484814
uniprot
proteins
pubmed
21080038
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21289099
uniprot
proteins
pubmed
21526763
uniprot
proteins
pubmed
22637475
uniprot
proteins
pubmed
22689054
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
2294010
uniprot
proteins
pubmed
23349634
uniprot
proteins
pubmed
23769672
uniprot
proteins
pubmed
23921388
uniprot
proteins
pubmed
23990668
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24355926
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25601083
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26045166
uniprot
proteins
pubmed
26655470
uniprot
proteins
pubmed
26657846
uniprot
proteins
pubmed
26940976
uniprot
proteins
pubmed
27159390
uniprot
proteins
pubmed
28053106
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28286085
uniprot
proteins
pubmed
28332555
uniprot
proteins
pubmed
2840249
uniprot
proteins
pubmed
29497057
uniprot
proteins
pubmed
29719251
uniprot
proteins
pubmed
32487760
uniprot
proteins
pubmed
33432092
uniprot
proteins
pubmed
36739529
uniprot
proteins
pubmed
38710792
uniprot
proteins
pubmed
9150946
uniprot
proteins
pubmed
9150948
uniprot
proteins
sequence_length
654
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000269|PubMed:21080038, ECO:0000269|PubMed:21289099, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:29497057}. Melanosome {ECO:0000269|PubMed:12643545}. Cytoplasm {ECO:0000250|UniProtKB:P20029}. Cell surface {ECO:0000269|PubMed:15098107, ECO:0000269|PubMed:20484814, ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:27159390, ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:12643545). Localizes to the cell surface of epithelial cells in response to high levels of free iron (PubMed:20484814, PubMed:24355926, PubMed:27159390). {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:20484814, ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:27159390}.
uniprot
proteins