Endoplasmic reticulum chaperone BiP (P11021)

Uniprot ID	P11021
Protein Name	Endoplasmic reticulum chaperone BiP
Gene Name	HSPA5
Species	Homo sapiens (Human)

Signal peptide^(a)	Y	Secretome P^(b)
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 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). .
GO - Molecular function	ATP binding : IEA:UniProtKB-KW ATPase activity : IDA:AgBase cadherin binding : HDA:BHF-UCL calcium ion binding : TAS:UniProtKB chaperone binding : TAS:BHF-UCL enzyme binding : IPI:BHF-UCL misfolded protein binding : IDA:UniProtKB protein domain specific binding : IPI:UniProtKB ribosome binding : IEA:Ensembl ubiquitin protein ligase binding : IPI:UniProtKB unfolded protein binding : TAS:UniProtKB
GO - Biological process	ATF6-mediated unfolded protein response : TAS:Reactome cellular response to antibiotic : IEA:Ensembl cellular response to calcium ion : IEA:Ensembl cellular response to cAMP : IEA:Ensembl cellular response to drug : IEA:Ensembl cellular response to gamma radiation : IEA:Ensembl cellular response to glucose starvation : IDA:UniProtKB cellular response to interleukin-4 : IEA:Ensembl cellular response to manganese ion : IEA:Ensembl cellular response to nerve growth factor stimulus : IEA:Ensembl cerebellar Purkinje cell layer development : IEA:Ensembl cerebellum structural organization : IEA:Ensembl endoplasmic reticulum unfolded protein response : TAS:BHF-UCL ER overload response : IEA:Ensembl IRE1-mediated unfolded protein response : TAS:Reactome maintenance of protein localization in endoplasmic reticulum : IMP:UniProtKB negative regulation of apoptotic process : IMP:UniProtKB negative regulation of IRE1-mediated unfolded protein response : ISS:UniProtKB negative regulation of protein homodimerization activity : ISS:UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway : IEA:Ensembl neuron apoptotic process : IEA:Ensembl neuron differentiation : IEA:Ensembl PERK-mediated unfolded protein response : TAS:Reactome positive regulation of cell migration : IMP:UniProtKB positive regulation of neuron projection development : IEA:Ensembl positive regulation of protein ubiquitination : IEA:Ensembl positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress : TAS:ParkinsonsUK-UCL protein folding in endoplasmic reticulum : TAS:ParkinsonsUK-UCL regulation of ATF6-mediated unfolded protein response : TAS:ParkinsonsUK-UCL regulation of IRE1-mediated unfolded protein response : TAS:ParkinsonsUK-UCL regulation of PERK-mediated unfolded protein response : TAS:ParkinsonsUK-UCL regulation of protein folding in endoplasmic reticulum : TAS:BHF-UCL response to cocaine : IEA:Ensembl response to methamphetamine hydrochloride : IEA:Ensembl stress response to metal ion : IEA:Ensembl substantia nigra development : HEP:UniProtKB toxin transport : IEA:Ensembl ubiquitin-dependent ERAD pathway : TAS:BHF-UCL

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^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}