HSPA5

Functionⁱ

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 ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). 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). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). 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.By similarity7 Publications

Caution

AMPylation was initially reported to take place at Ser-365 and Thr-366 in vitro, and promote activation of HSPA5/BiP (PubMed:25601083). However, it was later shown that AMPylation takes place at Thr-518 and leads to inactivation of HSPA5/BiP.By similarity1 Publication

Catalytic activityⁱ

ATP + H₂O = ADP + phosphate.1 Publication

Activity regulationⁱ

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).1 PublicationBy similarity1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	96	ATP1 Publication		1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	36 – 39	ATP1 Publication	4
Nucleotide bindingⁱ	227 – 229	ATP1 Publication	3
Nucleotide bindingⁱ	293 – 300	ATP1 Publication	8
Nucleotide bindingⁱ	364 – 367	ATP1 Publication	4

GO - Molecular functionⁱ

ATPase activity
Source: AgBase
Inferred from direct assayⁱ
- 20335166
ATPase activity, coupled
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
ATP binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cadherin binding
Source: BHF-UCL
Inferred from high throughput direct assayⁱ
- 25468996
calcium ion binding
Source: UniProtKB
Traceable author statementⁱ
- 16130169
chaperone binding
Source: BHF-UCL
Traceable author statementⁱ
- 19816510
enzyme binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 23921388
heat shock protein binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
misfolded protein binding
Source: UniProtKB
Inferred from direct assayⁱ
- 18400946
protein binding involved in protein folding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
protein domain specific binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 12411443
ribosome binding Source: Ensembl
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 8666824
unfolded protein binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

ATF6-mediated unfolded protein response Source: Reactome
cellular response to antibiotic Source: Ensembl
cellular response to calcium ion Source: Ensembl
cellular response to cAMP Source: Ensembl
cellular response to drug Source: Ensembl
cellular response to gamma radiation Source: Ensembl
cellular response to glucose starvation
Source: UniProtKB
Inferred from direct assayⁱ
- 10085239
cellular response to heat
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cellular response to interleukin-4 Source: Ensembl
cellular response to manganese ion Source: Ensembl
cellular response to nerve growth factor stimulus Source: Ensembl
cellular response to unfolded protein
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cerebellar Purkinje cell layer development Source: Ensembl
cerebellum structural organization Source: Ensembl
chaperone cofactor-dependent protein refolding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
endoplasmic reticulum unfolded protein response
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
ER overload response Source: Ensembl
IRE1-mediated unfolded protein response Source: Reactome
luteolysis Source: Ensembl
maintenance of protein localization in endoplasmic reticulum
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23990668
negative regulation of apoptotic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 10760948
- 12665508
negative regulation of IRE1-mediated unfolded protein response Source: UniProtKB
negative regulation of protein homodimerization activity Source: UniProtKB
negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
neuron apoptotic process Source: Ensembl
neuron differentiation Source: Ensembl
PERK-mediated unfolded protein response Source: Reactome
positive regulation of cell migration
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23990668
positive regulation of neuron projection development Source: Ensembl
positive regulation of protein ubiquitination Source: Ensembl
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 14685163
protein folding in endoplasmic reticulum
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22013210
protein refolding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
regulation of ATF6-mediated unfolded protein response
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22934019
regulation of IRE1-mediated unfolded protein response
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22934019
regulation of PERK-mediated unfolded protein response
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22934019
regulation of protein folding in endoplasmic reticulum
Source: BHF-UCL
Traceable author statementⁱ
- 19816510
response to cocaine Source: Ensembl
response to methamphetamine hydrochloride Source: Ensembl
response to unfolded protein
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
stress response to metal ion Source: Ensembl
substantia nigra development
Source: UniProtKB
Inferred from high throughput expression patternⁱ
- 22926577
toxin transport Source: Ensembl
ubiquitin-dependent ERAD pathway
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Chaperone, Hydrolase
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-114608 Platelet degranulation R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones R-HSA-381042 PERK regulates gene expression R-HSA-381070 IRE1alpha activates chaperones R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
SIGNORⁱ	P11021

Protein family/group databases

TCDBⁱ	1.A.33.1.6 the cation channel-forming heat shock protein-70 (hsp70) family

TCDBⁱ

1.A.33.1.6 the cation channel-forming heat shock protein-70 (hsp70) family

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Endoplasmic reticulum chaperone BiPCurated (EC:3.6.4.101 Publication) Alternative name(s): 78 kDa glucose-regulated protein1 Publication Short name: GRP-781 Publication Binding-immunoglobulin protein1 Publication Short name: BiP1 Publication Heat shock protein 70 family protein 5Curated Short name: HSP70 family protein 5Curated Heat shock protein family A member 5Imported Immunoglobulin heavy chain-binding protein1 Publication
Gene namesⁱ	Name:HSPA5Imported Synonyms:GRP781 Publication
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 9

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000044574.7
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:5238 HSPA5
MIMⁱ	138120 gene
neXtProtⁱ	NX_P11021

Keywords - Cellular componentⁱ

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Autoantigen in rheumatoid arthritis.1 Publication

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	229	T → A: Impaired ATPase activity. 1 Publication		1
Mutagenesisⁱ	585	K → R: Complete loss of in vitro methylation by METTL21A. 2 Publications		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	3309
Open Targets More...OpenTargetsⁱ	ENSG00000044574
PharmGKBⁱ	PA29504

Chemistry databases

ChEMBLⁱ	CHEMBL1781865
Drug and drug target database More...DrugBankⁱ	DB00945 Acetylsalicylic acid DB00025 Antihemophilic Factor (Recombinant)

Polymorphism and mutation databases

BioMutaⁱ	HSPA5
DMDMⁱ	14916999

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 18	2 PublicationsAdd BLAST		18
ChainⁱPRO_0000013566	19 – 654	Endoplasmic reticulum chaperone BiPAdd BLAST		636

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	86	PhosphoserineBy similarity	1
Modified residueⁱ	125	N6-acetyllysineBy similarity	1
Modified residueⁱ	160	Nitrated tyrosineBy similarity	1
Modified residueⁱ	213	N6-acetyllysineBy similarity	1
Modified residueⁱ	271	N6-acetyllysineBy similarity	1
Modified residueⁱ	326	N6-acetyllysineBy similarity	1
Cross-linkⁱ	352	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	353	N6-acetyllysine; alternateBy similarity	1
Cross-linkⁱ	353	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Modified residueⁱ	447	N6-succinyllysineBy similarity	1
Modified residueⁱ	492	Omega-N-methylarginineBy similarity	1
Modified residueⁱ	518	O-AMP-threonine; alternateBy similarity	1
Modified residueⁱ	518	Phosphothreonine; alternateCombined sources	1
Modified residueⁱ	585	N6,N6,N6-trimethyllysine; by METTL21A; in vitroCombined sources2 Publications	1
Modified residueⁱ	585	N6,N6-dimethyllysine; alternateCombined sources	1
Modified residueⁱ	585	N6-methyllysine; alternateCombined sources	1
Modified residueⁱ	591	N6-methyllysineCombined sources	1
Modified residueⁱ	643	PhosphothreonineBy similarity	1
Modified residueⁱ	648	PhosphothreonineBy similarity	1

Post-translational modificationⁱ

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).By similarity1 Publication

Keywords - PTMⁱ

Acetylation, Isopeptide bond, Methylation, Nitration, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	P11021
PaxDbⁱ	P11021
PeptideAtlas More...PeptideAtlasⁱ	P11021
PRIDEⁱ	P11021
ProteomicsDBⁱ	52688
TopDownProteomicsⁱ	P11021

2D gel databases

DOSAC-COBS 2D-PAGE database More...DOSAC-COBS-2DPAGEⁱ	P11021
USC-OGP 2-DE database More...OGPⁱ	P11021
REPRODUCTION-2DPAGE More...REPRODUCTION-2DPAGEⁱ	P11021
SWISS-2DPAGEⁱ	P11021
UCD-2DPAGEⁱ	P11021

PTM databases

iPTMnetⁱ	P11021
PhosphoSitePlusⁱ	P11021
SwissPalmⁱ	P11021

Expressionⁱ

Inductionⁱ

By endoplasmic reticulum stress.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000044574 Expressed in 243 organ(s), highest expression level in vena cava
CleanExⁱ	HS_HSPA5
ExpressionAtlasⁱ	P11021 baseline and differential
Genevisibleⁱ	P11021 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB005221 HPA038845 HPA038846

HPAⁱ

CAB005221
HPA038845
HPA038846

Interactionⁱ

Subunit structureⁱ

Monomer and homooligomer; homooligomerization via the interdomain linker inactivates the chaperone activity and acts as a storage of HSPA5/BiP molecules (By similarity). Interacts with DNAJC1 (via J domain) (By similarity). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX (By similarity). Interacts with TMEM132A and TRIM21 (PubMed:12699405). May form a complex with ERLEC1, OS9, SEL1L and SYVN1 (PubMed:18264092,PubMed:18502753). Interacts with DNAJC10 (PubMed:12411443, PubMed:23769672). Interacts with DNAJB9/ERdj4; leading to recruit HSPA5/BiP to ERN1/IRE1 (By similarity). Interacts with ERN1/IRE1; interaction takes place following interaction with DNAJB9/ERdj4 and leads to inactivate ERN1/IRE1 (By similarity). Interacts with MX1 (By similarity). Interacts with METTL23 (PubMed:23349634). Interacts with CEMIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration (PubMed:23990668). Interacts with PCSK4 form; the interaction takes place in the endoplasmic reticulum (PubMed:21080038). Interacts with CIPC (PubMed:26657846). Interacts with CCDC88B (via C-terminus); the interaction opposes ERN1-mediated JNK activation, protecting against apoptosis (PubMed:21289099). Interacts with INPP5K; necessary for INPP5K localization at the endoplasmic reticulum (PubMed:26940976). Interacts with MANF; the interaction is direct (PubMed:22637475). Interacts with LOXL2; leading to activate the ERN1/IRE1-XBP1 pathway of the unfolded protein response (PubMed:28332555).By similarity13 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
	Q6T424	3	EBI-354921,EBI-7888150
AKT1	P31749	2	EBI-354921,EBI-296087
ATF6	P18850	2	EBI-354921,EBI-852157
DMKN	Q6E0U4	3	EBI-354921,EBI-7943171
DNAJB11	Q9UBS4	3	EBI-354921,EBI-713113
Dnajc3	Q91YW3	2	EBI-354921,EBI-8381770	From Mus musculus.
EIF2AK3	Q9NZJ5	4	EBI-354921,EBI-766076
ERN1	O75460	3	EBI-354921,EBI-371750
ERN1	O75460-1	4	EBI-354921,EBI-15600828
PAWR	Q96IZ0	8	EBI-354921,EBI-595869
Pawr	Q62627	4	EBI-354921,EBI-1187240	From Rattus norvegicus.
RAF1	P04049	5	EBI-354921,EBI-365996
SEC61A1	P61619	3	EBI-354921,EBI-358919

GO - Molecular functionⁱ

cadherin binding
Source: BHF-UCL
Inferred from high throughput direct assayⁱ
- 25468996
chaperone binding
Source: BHF-UCL
Traceable author statementⁱ
- 19816510
enzyme binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 23921388
heat shock protein binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
misfolded protein binding
Source: UniProtKB
Inferred from direct assayⁱ
- 18400946
protein binding involved in protein folding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
protein domain specific binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 12411443
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 8666824
unfolded protein binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	109541, 574 interactors
CORUMⁱ	P11021
Database of interacting proteins More...DIPⁱ	DIP-33189N
ELMⁱ	P11021
IntActⁱ	P11021, 196 interactors
Molecular INTeraction database More...MINTⁱ	P11021
STRINGⁱ	9606.ENSP00000324173

Chemistry databases

BindingDBⁱ

P11021

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	31 – 34	Combined sources	4
Beta strandⁱ	37 – 45	Combined sources	9
Beta strandⁱ	47 – 52	Combined sources	6
Beta strandⁱ	60 – 63	Combined sources	4
Beta strandⁱ	66 – 68	Combined sources	3
Beta strandⁱ	74 – 76	Combined sources	3
Helixⁱ	78 – 82	Combined sources	5
Helixⁱ	84 – 86	Combined sources	3
Helixⁱ	88 – 90	Combined sources	3
Beta strandⁱ	91 – 93	Combined sources	3
Helixⁱ	95 – 97	Combined sources	3
Turnⁱ	98 – 100	Combined sources	3
Helixⁱ	106 – 114	Combined sources	9
Beta strandⁱ	116 – 122	Combined sources	7
Beta strandⁱ	125 – 131	Combined sources	7
Beta strandⁱ	137 – 140	Combined sources	4
Helixⁱ	142 – 161	Combined sources	20
Beta strandⁱ	167 – 172	Combined sources	6
Helixⁱ	178 – 190	Combined sources	13
Beta strandⁱ	194 – 200	Combined sources	7
Helixⁱ	201 – 208	Combined sources	8
Turnⁱ	209 – 212	Combined sources	4
Beta strandⁱ	215 – 225	Combined sources	11
Beta strandⁱ	230 – 238	Combined sources	9
Beta strandⁱ	241 – 250	Combined sources	10
Helixⁱ	255 – 274	Combined sources	20
Helixⁱ	278 – 280	Combined sources	3
Helixⁱ	282 – 298	Combined sources	17
Turnⁱ	299 – 301	Combined sources	3
Beta strandⁱ	302 – 313	Combined sources	12
Beta strandⁱ	316 – 323	Combined sources	8
Helixⁱ	324 – 337	Combined sources	14
Helixⁱ	339 – 348	Combined sources	10
Helixⁱ	353 – 355	Combined sources	3
Beta strandⁱ	358 – 363	Combined sources	6
Helixⁱ	364 – 367	Combined sources	4
Helixⁱ	369 – 378	Combined sources	10
Turnⁱ	379 – 381	Combined sources	3
Turnⁱ	390 – 392	Combined sources	3
Helixⁱ	393 – 405	Combined sources	13
Beta strandⁱ	415 – 419	Combined sources	5
Beta strandⁱ	424 – 428	Combined sources	5
Turnⁱ	429 – 431	Combined sources	3
Beta strandⁱ	433 – 437	Combined sources	5
Beta strandⁱ	442 – 451	Combined sources	10
Beta strandⁱ	461 – 468	Combined sources	8
Helixⁱ	473 – 475	Combined sources	3
Beta strandⁱ	476 – 484	Combined sources	9
Beta strandⁱ	491 – 493	Combined sources	3
Beta strandⁱ	497 – 503	Combined sources	7
Beta strandⁱ	509 – 515	Combined sources	7
Turnⁱ	516 – 518	Combined sources	3
Beta strandⁱ	521 – 526	Combined sources	6
Turnⁱ	528 – 531	Combined sources	4
Helixⁱ	535 – 576	Combined sources	42
Turnⁱ	579 – 581	Combined sources	3
Helixⁱ	582 – 585	Combined sources	4
Helixⁱ	588 – 607	Combined sources	20
Helixⁱ	613 – 631	Combined sources	19

Show more details

3D structure databases

ProteinModelPortalⁱ	P11021
SMRⁱ	P11021
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P11021

EvolutionaryTraceⁱ

P11021

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	125 – 280	Nucleotide-binding (NBD)1 PublicationAdd BLAST	156
Regionⁱ	409 – 419	Interdomain linkerBy similarityAdd BLAST	11
Regionⁱ	420 – 500	Substrate-binding (SBD)1 PublicationAdd BLAST	81

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	651 – 654	Prevents secretion from ERSequence analysis		4

Domainⁱ

The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one HSPA5/BiP molecule as a typical substrate of an adjacent HSPA5/BiP molecule. HSPA5/BiP oligomerization inactivates participating HSPA5/BiP protomers. HSPA5/BiP oligomers probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers.By similarity

Sequence similaritiesⁱ

Belongs to the heat shock protein 70 family.Curated

Keywords - Domainⁱ

Signal

Phylogenomic databases

eggNOGⁱ	KOG0101 Eukaryota COG0443 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00930000150862
HOGENOMⁱ	HOG000228135
HOVERGENⁱ	HBG051845
InParanoidⁱ	P11021
KEGG Orthology (KO) More...KOⁱ	K09490
OMAⁱ	CVGVMQK
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0352
PhylomeDBⁱ	P11021
TreeFamⁱ	TF105044

Family and domain databases

Gene3Dⁱ	1.20.1270.10, 1 hit 2.60.34.10, 1 hit
InterProⁱ	View protein in InterPro IPR018181 Heat_shock_70_CS IPR029048 HSP70_C_sf IPR029047 HSP70_peptide-bd_sf IPR013126 Hsp_70_fam
PANTHERⁱ	PTHR19375 PTHR19375, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00012 HSP70, 1 hit
PRINTSⁱ	PR00301 HEATSHOCK70
SUPFAMⁱ	SSF100920 SSF100920, 1 hit SSF100934 SSF100934, 1 hit
PROSITEⁱ	View protein in PROSITE PS00014 ER_TARGET, 1 hit 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.

P11021-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV 
        60         70         80         90        100
EIIANDQGNR ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG 
       110        120        130        140        150
RTWNDPSVQQ DIKFLPFKVV EKKTKPYIQV DIGGGQTKTF APEEISAMVL 
       160        170        180        190        200
TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ RQATKDAGTI AGLNVMRIIN 
       210        220        230        240        250
EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG VFEVVATNGD 
       260        270        280        290        300
THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS 
       310        320        330        340        350
SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD 
       360        370        380        390        400
LKKSDIDEIV LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV 
       410        420        430        440        450
QAGVLSGDQD TGDLVLLDVC PLTLGIETVG GVMTKLIPRN TVVPTKKSQI 
       460        470        480        490        500
FSTASDNQPT VTIKVYEGER PLTKDNHLLG TFDLTGIPPA PRGVPQIEVT 
       510        520        530        540        550
FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER MVNDAEKFAE 
       560        570        580        590        600
EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE 
       610        620        630        640        650
KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE 

KDEL

Length:654

Mass (Da):72,333

Last modified:July 11, 2001 - v2

Checksum:ⁱ59B7D8D85BC32A00

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	297	Missing in AAA52614 (PubMed:2840249).Curated	1
Sequence conflictⁱ	297	Missing in CAA61201 (Ref. 2) Curated	1
Sequence conflictⁱ	418	D → H in AAA52614 (PubMed:2840249).Curated	1
Sequence conflictⁱ	418	D → H in CAA61201 (Ref. 2) Curated	1
Sequence conflictⁱ	439	R → S in AAA52614 (PubMed:2840249).Curated	1
Sequence conflictⁱ	439	R → S in CAA61201 (Ref. 2) Curated	1
Sequence conflictⁱ	447	K → N in AAA52614 (PubMed:2840249).Curated	1
Sequence conflictⁱ	447	K → N in CAA61201 (Ref. 2) Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_025815	543	N → H1 PublicationCorresponds to variant dbSNP:rs35356639Ensembl.		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M19645 Genomic DNA Translation: AAA52614.1 X87949 mRNA Translation: CAA61201.1 AJ271729 mRNA Translation: CAB71335.1 AF216292 mRNA Translation: AAF42836.1 DQ385847 Genomic DNA Translation: ABD04090.1 AL354710 Genomic DNA No translation available. CH471090 Genomic DNA Translation: EAW87620.1 BC020235 mRNA Translation: AAH20235.1 X59969 Genomic DNA Translation: CAA42595.1 AF188611 mRNA Translation: AAF13605.1 Sequence problems.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS6863.1
PIRⁱ	A29821
NCBI Reference Sequences More...RefSeqⁱ	NP_005338.1, NM_005347.4
UniGeneⁱ	Hs.743241

Genome annotation databases

Ensemblⁱ	ENST00000324460; ENSP00000324173; ENSG00000044574
GeneIDⁱ	3309
KEGGⁱ	hsa:3309

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P11021	Epididymis secretory sperm binding protein Li 89n		HUMAN		654	UniRef100_P11021
HSPA5 isoform 1		PANTR		654
78 kDa glucose-regulated protein		MACMU		654
Endoplasmic reticulum chaperone BiP		PONAB		654
Uncharacterized protein		COLAP		654
+9

Protein	Similar proteins		Species	Score	Length	Source
P11021	Endoplasmic reticulum chaperone BiP		XENLA		658	UniRef90_P11021
Endoplasmic reticulum chaperone BiP		MOUSE		655
Endoplasmic reticulum chaperone BiP		BOVIN		655
Endoplasmic reticulum chaperone BiP	)	CRIGR		654
Endoplasmic reticulum chaperone BiP		MESAU		654
+329

Protein	Similar proteins		Species	Score	Length	Source
P11021	Heat shock 70 kDa protein 1A	)	HUMAN		641	UniRef50_P0DMV8
Heat shock 70 kDa protein 1		PONAB		641
Heat shock 70 kDa protein 1B		MOUSE		642
Heat shock 70 kDa protein 1B		BOVIN		641
Heat shock 70 kDa protein 1B		BOSMU		641
+2027

Cross-referencesⁱ

Web resourcesⁱ

NIEHS-SNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M19645 Genomic DNA Translation: AAA52614.1 X87949 mRNA Translation: CAA61201.1 AJ271729 mRNA Translation: CAB71335.1 AF216292 mRNA Translation: AAF42836.1 DQ385847 Genomic DNA Translation: ABD04090.1 AL354710 Genomic DNA No translation available. CH471090 Genomic DNA Translation: EAW87620.1 BC020235 mRNA Translation: AAH20235.1 X59969 Genomic DNA Translation: CAA42595.1 AF188611 mRNA Translation: AAF13605.1 Sequence problems.
CCDSⁱ	CCDS6863.1
PIRⁱ	A29821
RefSeqⁱ	NP_005338.1, NM_005347.4
UniGeneⁱ	Hs.743241

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	3IUC	X-ray	2.40	A/C	26-410	[»]
	3LDL	X-ray	2.30	A/B	26-407	[»]
	3LDN	X-ray	2.20	A/B	26-407	[»]
	3LDO	X-ray	1.95	A/B	26-407	[»]
	3LDP	X-ray	2.20	A/B	26-407	[»]
	5E84	X-ray	2.99	A/B/C/D/E/F	25-633	[»]
	5E85	X-ray	2.57	A	418-637	[»]
	5E86	X-ray	2.68	A	418-637	[»]
	5EVZ	X-ray	1.85	A/B	26-407	[»]
	5EX5	X-ray	1.90	A/B	26-407	[»]
	5EXW	X-ray	1.90	A/B	26-407	[»]
	5EY4	X-ray	1.86	A/B	26-407	[»]
	5F0X	X-ray	1.60	A/B	26-407	[»]
	5F1X	X-ray	1.90	A/B	26-407	[»]
	5F2R	X-ray	2.15	A/B	26-407	[»]
	6ASY	X-ray	1.85	A/B	25-633	[»]
ProteinModelPortalⁱ	P11021
SMRⁱ	P11021
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	109541, 574 interactors
CORUMⁱ	P11021
DIPⁱ	DIP-33189N
ELMⁱ	P11021
IntActⁱ	P11021, 196 interactors
MINTⁱ	P11021
STRINGⁱ	9606.ENSP00000324173

Chemistry databases

BindingDBⁱ	P11021
ChEMBLⁱ	CHEMBL1781865
DrugBankⁱ	DB00945 Acetylsalicylic acid DB00025 Antihemophilic Factor (Recombinant)

Protein family/group databases

TCDBⁱ	1.A.33.1.6 the cation channel-forming heat shock protein-70 (hsp70) family

TCDBⁱ

1.A.33.1.6 the cation channel-forming heat shock protein-70 (hsp70) family

PTM databases

iPTMnetⁱ	P11021
PhosphoSitePlusⁱ	P11021
SwissPalmⁱ	P11021

Polymorphism and mutation databases

BioMutaⁱ	HSPA5
DMDMⁱ	14916999

2D gel databases

DOSAC-COBS-2DPAGEⁱ	P11021
OGPⁱ	P11021
REPRODUCTION-2DPAGEⁱ	P11021
SWISS-2DPAGEⁱ	P11021
UCD-2DPAGEⁱ	P11021

Proteomic databases

EPDⁱ	P11021
PaxDbⁱ	P11021
PeptideAtlasⁱ	P11021
PRIDEⁱ	P11021
ProteomicsDBⁱ	52688
TopDownProteomicsⁱ	P11021

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	3309
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000324460; ENSP00000324173; ENSG00000044574
GeneIDⁱ	3309
KEGGⁱ	hsa:3309

Organism-specific databases

CTDⁱ	3309
DisGeNETⁱ	3309
EuPathDBⁱ	HostDB:ENSG00000044574.7
GeneCardsⁱ	HSPA5
HGNCⁱ	HGNC:5238 HSPA5
HPAⁱ	CAB005221 HPA038845 HPA038846
MIMⁱ	138120 gene
neXtProtⁱ	NX_P11021
OpenTargetsⁱ	ENSG00000044574
PharmGKBⁱ	PA29504
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0101 Eukaryota COG0443 LUCA
GeneTreeⁱ	ENSGT00930000150862
HOGENOMⁱ	HOG000228135
HOVERGENⁱ	HBG051845
InParanoidⁱ	P11021
KOⁱ	K09490
OMAⁱ	CVGVMQK
OrthoDBⁱ	EOG091G0352
PhylomeDBⁱ	P11021
TreeFamⁱ	TF105044

Enzyme and pathway databases

Reactomeⁱ	R-HSA-114608 Platelet degranulation R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones R-HSA-381042 PERK regulates gene expression R-HSA-381070 IRE1alpha activates chaperones R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
SIGNORⁱ	P11021

Miscellaneous databases

ChiTaRSⁱ	HSPA5 human
EvolutionaryTraceⁱ	P11021
GeneWikiⁱ	Binding_immunoglobulin_protein
GenomeRNAiⁱ	3309
Protein Ontology More...PROⁱ	PR:P11021
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000044574 Expressed in 243 organ(s), highest expression level in vena cava
CleanExⁱ	HS_HSPA5
ExpressionAtlasⁱ	P11021 baseline and differential
Genevisibleⁱ	P11021 HS

Family and domain databases

Gene3Dⁱ	1.20.1270.10, 1 hit 2.60.34.10, 1 hit
InterProⁱ	View protein in InterPro IPR018181 Heat_shock_70_CS IPR029048 HSP70_C_sf IPR029047 HSP70_peptide-bd_sf IPR013126 Hsp_70_fam
PANTHERⁱ	PTHR19375 PTHR19375, 1 hit
Pfamⁱ	View protein in Pfam PF00012 HSP70, 1 hit
PRINTSⁱ	PR00301 HEATSHOCK70
SUPFAMⁱ	SSF100920 SSF100920, 1 hit SSF100934 SSF100934, 1 hit
PROSITEⁱ	View protein in PROSITE PS00014 ER_TARGET, 1 hit PS00297 HSP70_1, 1 hit PS00329 HSP70_2, 1 hit PS01036 HSP70_3, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	BIP_HUMAN
Accessionⁱ	P11021Primary (citable) accession number: P11021 Secondary accession number(s): B0QZ61 , Q2EF78, Q9NPF1, Q9UK02
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
	Last sequence update:	July 11, 2001
	Last modified:	November 7, 2018
	This is version 218 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM

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UniProtKB - P11021 (BIP_HUMAN)

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Endoplasmic reticulum chaperone BiP

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endoplasmic reticulum

Other locations

Endoplasmic reticulum

Extracellular region or secreted

Mitochondrion

Nucleus

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

2D gel databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ