Endoplasmic reticulum chaperone BiP (P06761)

Uniprot ID P06761
Protein Name Endoplasmic reticulum chaperone BiP
Gene Name Hspa5
Species Rattus norvegicus (Rat)
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 (By similarity). 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). 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. 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. .
GO - Molecular function
  • ATP binding : ISO:RGD
  • ATPase activity : ISS:UniProtKB
  • ATPase activity, coupled : IBA:GO_Central
  • enzyme binding : ISO:RGD
  • heat shock protein binding : IBA:GO_Central
  • misfolded protein binding : IDA:MGI
  • protein domain specific binding : ISO:RGD
  • protein folding chaperone : IBA:GO_Central
  • ribosome binding : ISO:RGD
  • ubiquitin protein ligase binding : ISO:RGD
  • unfolded protein binding : IPI:RGD
GO - Biological process
  • cellular response to antibiotic : IEP:RGD
  • cellular response to calcium ion : IEP:RGD
  • cellular response to cAMP : IEP:RGD
  • cellular response to drug : IEP:RGD
  • cellular response to gamma radiation : IEP:RGD
  • cellular response to glucose starvation : ISO:RGD
  • cellular response to interleukin-4 : ISO:RGD
  • cellular response to manganese ion : IEP:ParkinsonsUK-UCL
  • cellular response to nerve growth factor stimulus : IEP:RGD
  • cellular response to unfolded protein : IBA:GO_Central
  • cerebellar Purkinje cell layer development : ISO:RGD
  • cerebellum structural organization : ISO:RGD
  • chaperone cofactor-dependent protein refolding : IBA:GO_Central
  • endoplasmic reticulum unfolded protein response : ISO:RGD
  • ER overload response : ISO:RGD
  • IRE1-mediated unfolded protein response : ISO:RGD
  • luteolysis : IEP:RGD
  • maintenance of protein localization in endoplasmic reticulum : ISS:UniProtKB
  • negative regulation of apoptotic process : ISO:RGD
  • negative regulation of IRE1-mediated unfolded protein response : ISS:UniProtKB
  • negative regulation of protein-containing complex assembly : ISS:GO_Central
  • negative regulation of transforming growth factor beta receptor signaling pathway : ISO:RGD
  • neuron apoptotic process : IEP:RGD
  • neuron differentiation : IEP:RGD
  • positive regulation of cell migration : ISS:UniProtKB
  • positive regulation of neuron projection development : IMP:RGD
  • positive regulation of protein ubiquitination : ISO:RGD
  • posttranslational protein targeting to membrane, translocation : ISS:UniProtKB
  • protein refolding : IBA:GO_Central
  • proteolysis involved in cellular protein catabolic process : ISO:RGD
  • response to cocaine : IEP:RGD
  • response to endoplasmic reticulum stress : IDA:MGI
  • response to methamphetamine hydrochloride : IEP:RGD
  • response to radiation : IEP:RGD
  • response to unfolded protein : IBA:GO_Central
  • stress response to metal ion : IEP:RGD
  • toxin transport : ISO:RGD
  • ubiquitin-dependent ERAD pathway : IBA:GO_Central
Back
(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.