HSPA5 (BiP/GRP78) is the Hsp70-family molecular chaperone of the endoplasmic reticulum (ER) lumen. It enters the ER through a cleaved signal peptide and is retained there by a C-terminal KDEL retrieval motif. Its nucleotide-binding domain binds and hydrolyzes ATP, which allosterically controls client binding and release by the substrate-binding domain; the cycle is driven by ER J-domain co-chaperones (ERdj3/DNAJB11, ERdj4/DNAJB9, ERdj5/DNAJC10, Sec63) that stimulate ATP hydrolysis and nucleotide-exchange factors (SIL1, GRP170/HYOU1), and is further tuned by FICD-mediated AMPylation and oligomerization. BiP binds hydrophobic segments of nascent and misfolded secretory and membrane proteins, promoting their folding and assembly, retaining unfolded clients and delivering terminally misfolded ones to ER-associated degradation. It also assists Sec61-mediated translocation of a subset of precursors into the ER. BiP is the master luminal regulator of the unfolded protein response: in unstressed cells it binds the luminal domains of the transducers IRE1alpha (ERN1, recruited by ERdj4), PERK (EIF2AK3) and ATF6, keeping them inactive, and competition by accumulating unfolded proteins releases them to signal; BiP is itself a major UPR-induced gene. Minor stress-induced cytosolic and cell-surface pools exist, and surface GRP78 serves as an entry factor for several viruses and Mucorales fungi.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: TAS from an HUVEC proteomics paper; BiP is a recognized low-affinity, high-capacity Ca2+-binding protein of the ER lumen. Reason: Ca2+ buffering by abundant lumenal chaperones is plausible, but the cited proteomics paper does not demonstrate Ca2+ binding; not a core function. Supporting Evidence: PMID:16130169 namely, GRP78, GRP94, valosin-containing protein, proteinase inhibitor 9, cofilin |
| GO:0005515 protein binding | IPI PMID:11907036 Dimerization and release of molecular chaperone inhibition f... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer EIF2AK3/PERK, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:12356756 BAP, a mammalian BiP-associated protein, is a nucleotide exc... | MODIFY | Summary: IPI evidence for interaction with SIL1 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:12577067 A proteomics strategy to elucidate functional protein-protei... | REMOVE | Summary: IPI evidence for interaction with GRB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:12840015 Nuclear coactivator-62 kDa/Ski-interacting protein is a nucl... | REMOVE | Summary: IPI evidence for interaction with SNW1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18064632 GRP78 and Raf-1 cooperatively confer resistance to endoplasm... | REMOVE | Summary: IPI evidence for interaction with RAF1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18264092 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1... | REMOVE | Summary: IPI evidence for interaction with ERLEC1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18502753 Human XTP3-B forms an endoplasmic reticulum quality control ... | REMOVE | Summary: IPI evidence for interaction with OS9. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18502753 Human XTP3-B forms an endoplasmic reticulum quality control ... | REMOVE | Summary: IPI evidence for interaction with SYVN1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18502753 Human XTP3-B forms an endoplasmic reticulum quality control ... | REMOVE | Summary: IPI evidence for interaction with ERLEC1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18502753 Human XTP3-B forms an endoplasmic reticulum quality control ... | REMOVE | Summary: IPI evidence for interaction with SEL1L. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:18923428 Regulated release of ERdj3 from unfolded proteins by BiP. | MODIFY | Summary: IPI evidence for interaction with DNAJB11/ERdj3 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:18923430 Regulated association of misfolded endoplasmic reticulum lum... | MODIFY | Summary: IPI evidence for interaction with mouse Dnajc3/p58IPK (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:19632185 The tumor suppressor Par-4 activates an extrinsic pathway fo... | REMOVE | Summary: IPI evidence for interaction with rat Pawr/Par-4. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:19632185 The tumor suppressor Par-4 activates an extrinsic pathway fo... | REMOVE | Summary: IPI evidence for interaction with PAWR/Par-4. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:20335166 The Salmonella type III secretion effector, salmonella leuci... | MODIFY | Summary: IPI evidence for interaction with DNAJB11/ERdj3 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:20467437 Direct interaction between hnRNP-M and CDC5L/PLRG1 proteins ... | REMOVE | Summary: IPI evidence for interaction with SNW1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:20477988 Role of the lectin VIP36 in post-ER quality control of human... | REMOVE | Summary: IPI evidence for interaction with LMAN2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: IPI evidence for interaction with GRB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:22613557 Identification of a potential tumor differentiation factor r... | REMOVE | Summary: IPI evidence for interaction with tumor differentiation factor. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:22689054 GRP78 regulates clusterin stability, retrotranslocation and ... | REMOVE | Summary: IPI evidence for interaction with clusterin. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:22735594 Dermokine-Ξ² impairs ERK signaling through direct binding to ... | REMOVE | Summary: IPI evidence for interaction with DMKN. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:22796945 BiP-mediated closing of the Sec61 channel limits Ca2+ leakag... | REMOVE | Summary: IPI evidence for interaction with SEC61A1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:23220234 Dimerization of pro-oncogenic protein Anterior Gradient 2 is... | REMOVE | Summary: IPI evidence for interaction with AGR2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:23349634 A newly uncovered group of distantly related lysine methyltr... | REMOVE | Summary: IPI evidence for interaction with METTL23. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:23769672 ERdj5 is the ER reductase that catalyzes the removal of non-... | MODIFY | Summary: IPI evidence for interaction with DNAJC10/ERdj5 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:23990668 Unraveling the role of KIAA1199, a novel endoplasmic reticul... | REMOVE | Summary: IPI evidence for interaction with CEMIP/KIAA1199. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: IPI evidence for interaction with ERBB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: IPI evidence for interaction with PDIA6. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | MODIFY | Summary: IPI evidence for interaction with DNAJB11/ERdj3 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:24473200 SIL1, a causative cochaperone gene of Marinesco-SΓΆjgren synd... | MODIFY | Summary: IPI evidence for interaction with SIL1 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:25601083 A novel link between Fic (filamentation induced by cAMP)-med... | REMOVE | Summary: IPI evidence for interaction with FICD (BiP AMPylase). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI evidence for interaction with HSP90B1/GRP94 (ER chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: IPI evidence for interaction with HYOU1/GRP170 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:26551274 IRE1Ξ± is an endogenous substrate of endoplasmic-reticulum-as... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer ERN1/IRE1, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:27238082 Compounds Triggering ER Stress Exert Anti-Melanoma Effects a... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer ERN1/IRE1, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:27238082 Compounds Triggering ER Stress Exert Anti-Melanoma Effects a... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer ATF6, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:27238082 Compounds Triggering ER Stress Exert Anti-Melanoma Effects a... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer EIF2AK3/PERK, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI evidence for interaction with SIL1 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI evidence for interaction with DNAJB11/ERdj3 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:28869608 CNPY2 is a key initiator of the PERK-CHOP pathway of the unf... | REMOVE | Summary: IPI evidence for interaction with mouse Cnpy2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:28869608 CNPY2 is a key initiator of the PERK-CHOP pathway of the unf... | REMOVE | Summary: IPI evidence for interaction with the UPR transducer mouse Eif2ak3/PERK, whose luminal domain BiP binds in unstressed cells. Reason: Generic protein binding is uninformative; the interaction itself is real and central to UPR regulation, but it is captured more informatively by the existing protein sequestering activity, kinase inhibitor activity and regulation-of-UPR-branch annotations. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005515 protein binding | IPI PMID:29887526 Middle East respiratory syndrome coronavirus and bat coronav... | REMOVE | Summary: IPI evidence for interaction with MERS-CoV spike. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MODIFY | Summary: IPI evidence for interaction with HSP90B1/GRP94 (ER chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: IPI evidence for interaction with PDIA6. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MODIFY | Summary: IPI evidence for interaction with HYOU1/GRP170 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:31258504 Identification of Cellular Pathogenicity Markers for SIL1 Mu... | MODIFY | Summary: IPI evidence for interaction with SIL1 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: IPI evidence for interaction with ERBB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: IPI evidence for interaction with GRB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with APP. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with SNW1. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with APP. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI evidence for interaction with SIL1 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI evidence for interaction with DNAJB9/ERdj4 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI evidence for interaction with DNAJB11/ERdj3 (J-domain co-chaperone). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI evidence for interaction with HYOU1/GRP170 (nucleotide exchange factor). Reason: Generic protein binding is uninformative. The partner is an ER chaperone/co-chaperone that regulates the BiP ATPase cycle (J-domain proteins stimulate ATP hydrolysis; NEFs exchange nucleotide) or cooperates with BiP in ER chaperone complexes, so protein-folding chaperone binding (GO:0051087) is the informative replacement. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0005515 protein binding | IPI PMID:33965375 The chaperone GRP78 is a host auxiliary factor for SARS-CoV-... | REMOVE | Summary: IPI evidence for interaction with SARS-CoV-2 spike. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:33965375 The chaperone GRP78 is a host auxiliary factor for SARS-CoV-... | REMOVE | Summary: IPI evidence for interaction with ACE2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:34615619 Possible Involvement of Adipose Tissue in Patients With Olde... | REMOVE | Summary: IPI evidence for interaction with SARS-CoV-2 spike. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:34615619 Possible Involvement of Adipose Tissue in Patients With Olde... | REMOVE | Summary: IPI evidence for interaction with ACE2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: IPI evidence for interaction with GORASP2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: IPI evidence for interaction with ERBB2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with GORASP2. Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: IPI evidence for interaction with a partner protein (large-scale or peptide-array interaction screen). Reason: Generic protein binding is uninformative about HSPA5 molecular function; removal does not imply the interaction is false. Many such partners are folding clients, ERAD components or proteins detected in high-throughput screens. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0005524 ATP binding | IDA PMID:26655470 Close and Allosteric Opening of the Polypeptide-Binding Site... | ACCEPT | Summary: BiP binds ATP in its nucleotide-binding domain; ATP binding allosterically couples the NBD and SBD to accelerate client binding/release. Reason: Intrinsic to the Hsp70 chaperone cycle; structurally demonstrated for human BiP. Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: BiP binds ATP in its nucleotide-binding domain; ATP binding allosterically couples the NBD and SBD to accelerate client binding/release. Reason: Intrinsic to the Hsp70 chaperone cycle; structurally demonstrated for human BiP. Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Detected in a proteomic analysis of the human sperm nucleus. Reason: High-throughput detection of an abundant ER chaperone in a nuclear preparation; at most a minor non-ER pool, not the functional compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from the BiP-branch node PTN001834223 for nucleus. Reason: BiP is a KDEL-retained ER lumenal protein; minor stress-associated nuclear pools have been reported, but nucleus is not its functional compartment. Kept as non-core for consistency with the rat Hspa5 review and the PTHR19375 family assessment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen PMID:11943137 several reports have suggested that GRP78 and its mutant forms may also be associated with cytosol, membrane and nuclear fractions, as well as the cell surface |
| GO:0005634 nucleus | IMP PMID:11943137 Coupling endoplasmic reticulum stress to the cell death prog... | KEEP AS NON CORE | Summary: PMID:11943137 discusses reports of GRP78 in nuclear fractions; the study itself focuses on stress-induced cytosolic and transmembrane pools. Reason: Minor non-ER pools are reported but the functional compartment is the ER lumen. Supporting Evidence: PMID:11943137 several reports have suggested that GRP78 and its mutant forms may also be associated with cytosol, membrane and nuclear fractions, as well as the cell surface PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Stress-induced cytosolic pools of GRP78 have been reported (e.g. upon ER stress or in association with retrotranslocated clusterin). Reason: Supported minor/conditional location; the core compartment is the ER lumen. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. |
| GO:0005737 cytoplasm | IDA PMID:22689054 GRP78 regulates clusterin stability, retrotranslocation and ... | KEEP AS NON CORE | Summary: Stress-induced cytosolic pools of GRP78 have been reported (e.g. upon ER stress or in association with retrotranslocated clusterin). Reason: Supported minor/conditional location; the core compartment is the ER lumen. Supporting Evidence: PMID:22689054 GRP78 (Bip) associates with CLU under ER stress conditions to facilitate its retrotranslocation and redistribution to the mitochondria. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Stress-induced cytosolic pools of GRP78 have been reported (e.g. upon ER stress or in association with retrotranslocated clusterin). Reason: Supported minor/conditional location; the core compartment is the ER lumen. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stress-induced cytosolic pools of GRP78 have been reported (e.g. upon ER stress or in association with retrotranslocated clusterin). Reason: Supported minor/conditional location; the core compartment is the ER lumen. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. |
| GO:0005739 mitochondrion | IDA PMID:22689054 GRP78 regulates clusterin stability, retrotranslocation and ... | KEEP AS NON CORE | Summary: GRP78 co-redistributes with clusterin to mitochondria under ER stress in prostate cancer cells. Reason: Conditional, cell-type-specific observation; not the core compartment. Supporting Evidence: PMID:22689054 GRP78 (Bip) associates with CLU under ER stress conditions to facilitate its retrotranslocation and redistribution to the mitochondria. |
| GO:0005783 endoplasmic reticulum | IDA PMID:16223484 The C-terminal region of cis-retinol/androgen dehydrogenase ... | ACCEPT | Summary: BiP is an ER-resident chaperone. Reason: Correct; the ER lumen is the more specific core location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt /note="Prevents secretion from ER" |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: BiP is an ER-resident chaperone. Reason: Correct; the ER lumen is the more specific core location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt /note="Prevents secretion from ER" |
| GO:0005783 endoplasmic reticulum | IMP PMID:11943137 Coupling endoplasmic reticulum stress to the cell death prog... | ACCEPT | Summary: BiP is an ER-resident chaperone. Reason: Correct; the ER lumen is the more specific core location. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. |
| GO:0005783 endoplasmic reticulum | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | ACCEPT | Summary: BiP is an ER-resident chaperone. Reason: Correct; the ER lumen is the more specific core location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt /note="Prevents secretion from ER" |
| GO:0005788 endoplasmic reticulum lumen | EXP PMID:29497057 Conserved roles of C. elegans and human MANFs in sulfatide b... | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: PMID:29497057 The uptaken Hs-MANF appeared to extensively co-localize with the MANF-interacting protein GRP78 (i.e. the ER resident chaperone BIP) file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | IBA GO_REF:0000033 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | IDA PMID:19538957 Activation of mammalian IRE1alpha upon ER stress depends on ... | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: PMID:19538957 These results suggest that in contrast to yeast Ire1, the regulation of mammalian IRE1alpha strongly depends on the dissociation of BiP. file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | IDA PMID:21289099 Protective role of Gipie, a Girdin family protein, in endopl... | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: PMID:21289099 Gipie stabilizes the interaction between GRP78 and the ER stress sensor inositol-requiring protein 1 (IRE1) at the ER, leading to the attenuation of IRE1-induced c-Jun N-terminal kinase (JNK) activation. file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000120 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-381086 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-381158 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-381217 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9921802 | ACCEPT | Summary: BiP is a soluble ER lumenal Hsp70 retained by its C-terminal KDEL signal. Reason: Core location, supported by multiple experimental and phylogenetic (IBA, BiP-branch node) lines of evidence. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:11181571 WFS1 (Wolfram syndrome 1) gene product: predominant subcellu... | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000107 | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:11943137 Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1791150 | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:29719251 We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to tran file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-381086 | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:29719251 We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to tran file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-381158 | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:29719251 We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to tran file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-381217 | ACCEPT | Summary: BiP associates peripherally with the luminal face of the ER membrane, at the Sec61 translocon and bound to the luminal domains of the UPR transducers. Reason: Peripheral ER membrane association is functionally important (translocation, sensor repression); BiP itself has no transmembrane segment. Supporting Evidence: PMID:29719251 We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to tran file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IDA PMID:15308636 Proteomics of endoplasmic reticulum-Golgi intermediate compa... | KEEP AS NON CORE | Summary: BiP was detected in purified ERGIC membranes; KDEL-bearing lumenal proteins cycle through the ERGIC and are retrieved. Reason: Consistent with KDEL-receptor retrieval cycling; not the functional compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt /note="Prevents secretion from ER" |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BiP was detected in purified ERGIC membranes; KDEL-bearing lumenal proteins cycle through the ERGIC and are retrieved. Reason: Consistent with KDEL-receptor retrieval cycling; not the functional compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt /note="Prevents secretion from ER" |
| GO:0005829 cytosol | IDA PMID:22689054 GRP78 regulates clusterin stability, retrotranslocation and ... | KEEP AS NON CORE | Summary: Stress-induced cytosolic pools of GRP78 have been reported (e.g. upon ER stress or in association with retrotranslocated clusterin). Reason: Supported minor/conditional location; the core compartment is the ER lumen. Supporting Evidence: PMID:22689054 GRP78 (Bip) associates with CLU under ER stress conditions to facilitate its retrotranslocation and redistribution to the mitochondria. |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic orthology transfer of plasma membrane localization. Reason: A cell-surface pool of GRP78 is documented (including as a viral/fungal receptor), but it is a context-specific moonlighting location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | MARK AS OVER ANNOTATED | Summary: High-throughput or proteomic detection associating BiP with focal adhesion. Reason: BiP is among the most abundant ER lumenal proteins and is a frequent co-purifying contaminant in proteomic and interactome studies; this does not establish a function or location in this structure. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0008180 COP9 signalosome | IDA PMID:18850735 Characterization of the human COP9 signalosome complex using... | MARK AS OVER ANNOTATED | Summary: High-throughput or proteomic detection associating BiP with COP9 signalosome. Reason: BiP is among the most abundant ER lumenal proteins and is a frequent co-purifying contaminant in proteomic and interactome studies; this does not establish a function or location in this structure. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0009986 cell surface | EXP PMID:15098107 Identification of GRP 78 (BiP) as a liver cell expressed rec... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | EXP PMID:20484814 The endothelial cell receptor GRP78 is required for mucormyc... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | EXP PMID:24355926 CotH3 mediates fungal invasion of host cells during mucormyc... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | EXP PMID:27159390 Bicarbonate correction of ketoacidosis alters host-pathogen ... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | EXP PMID:28053106 GRP78 Is an Important Host Factor for Japanese Encephalitis ... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | EXP PMID:33432092 A functional interaction between GRP78 and Zika virus E prot... | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0009986 cell surface | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cell-surface GRP78 acts as a host entry factor/receptor for several flaviviruses and for Mucorales CotH proteins. Reason: Well-documented condition-specific (e.g. high iron, infection) cell-surface pool; a moonlighting location rather than the core compartment. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Acts as a receptor for CotH proteins expressed by fungi of the order mucorales file:human/HSPA5/HSPA5-uniprot.txt Localizes to the cell surface of epithelial cells in response to high levels of free iron |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Annotation to bare membrane (HDA membrane proteome or IBA from the BiP-branch node). Reason: Uninformative for a soluble KDEL-retained lumenal protein whose membrane contact is peripheral; GO:0005789 ER membrane and GO:0005788 ER lumen already capture the localization (PTHR19375 family review treats this as a granularity issue). Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0016020 membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Annotation to bare membrane (HDA membrane proteome or IBA from the BiP-branch node). Reason: Uninformative for a soluble KDEL-retained lumenal protein whose membrane contact is peripheral; GO:0005789 ER membrane and GO:0005788 ER lumen already capture the localization (PTHR19375 family review treats this as a granularity issue). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001834223 Β· PTN001834223 SUPPORTS TRANSFER BiP-specific node (seeds are BiP orthologs, including human HSPA5); node placement is sound and also carries the accepted ER lumen, ER chaperone complex, UPR and ERAD assertions. The issue is only that bare membrane is uninformative for a soluble KDEL-retained lumenal protein (see PTHR19375 family review). Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0016887 ATP hydrolysis activity | EXP PMID:26655470 Close and Allosteric Opening of the Polypeptide-Binding Site... | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Reaction=ATP + H2O = ADP + phosphate + H(+) file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0016887 ATP hydrolysis activity | IDA PMID:20335166 The Salmonella type III secretion effector, salmonella leuci... | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: PMID:20335166 Here, we identified ERdj3, an endoplasmic reticulum lumenal chaperone of the Hsp40/DnaJ family, as a new target for SlrP. file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0016887 ATP hydrolysis activity | IDA PMID:23975754 Identification and characterization of interactions between ... | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: PMID:23975754 However, ABA was found to have only variable- and co-chaperone-independent effects on the ATPase activity of these proteins. file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Reaction=ATP + H2O = ADP + phosphate + H(+) file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0016887 ATP hydrolysis activity | ISS GO_REF:0000024 | ACCEPT | Summary: BiP hydrolyzes ATP in its NBD; hydrolysis, stimulated by J-domain co-chaperones, drives client capture in the Hsp70 cycle. Reason: Core enzymatic activity of the Hsp70 chaperone cycle (EC 3.6.4.10), conserved family-wide. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Reaction=ATP + H2O = ADP + phosphate + H(+) file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0019899 enzyme binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic (ARBA) enzyme binding, repeating the experimentally supported interaction of HSPA5 with a modifying enzyme of which it is a substrate. Reason: The same term is carried by the experimental row from the METTL21A methyltransferase study, which is kept as non-core because the interaction with a modifying enzyme is real although HSPA5 is its substrate. This machine-generated row repeats that claim; rows that share a term are judged alike, so it is kept as non-core with the experimental row rather than removed. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen |
| GO:0019899 enzyme binding | IPI PMID:23921388 Identification and characterization of a novel human methylt... | KEEP AS NON CORE | Summary: Binding to modifying enzymes (e.g. Hsp70 lysine methyltransferases) of which HSPA5 is a substrate. Reason: The cited study identified the lysine methyltransferase METTL21A as an enzyme that binds and methylates Hsp70-family proteins (PMID:23921388), and this row records the interaction of HSPA5 with such a modifying enzyme, so the annotation is true as stated. HSPA5 is the substrate in this interaction rather than a protein whose function is to bind enzymes, which makes the term peripheral to its chaperone activities, not wrong; the equivalent rows are retained for the cytosolic paralogs HSPA1A and HSPA1B. The row is kept as non-core rather than removed. Supporting Evidence: PMID:23921388 In this study, we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins. |
| GO:0019904 protein domain specific binding | IPI PMID:12411443 ERdj5, an endoplasmic reticulum (ER)-resident protein contai... | MODIFY | Summary: ERdj5 interacts via its DnaJ (J) domain with BiP in an ATP-dependent manner. Reason: The interaction is the classic J-domain co-chaperone/Hsp70 interaction; protein-folding chaperone binding is more informative than protein domain specific binding. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:12411443 In vitro experiments demonstrated that ERdj5 interacts via its DnaJ domain with BiP in an ATP-dependent manner. |
| GO:0021589 cerebellum structural organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer from mouse: Purkinje-cell-specific Grp78 deletion causes Purkinje cell degeneration and cerebellar atrophy. Reason: Reflects the requirement for BiP-dependent ER homeostasis for neuronal survival rather than a developmental patterning role; non-core. Supporting Evidence: PMID:19816510 In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator of UPR, is specifically eliminated in Purkinje cells (PCs). PMID:19816510 The mice show retarded growth and severe motor coordination defect by week 5 and cerebellar atrophy by week 13. |
| GO:0021680 cerebellar Purkinje cell layer development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer from mouse: Purkinje-cell-specific Grp78 deletion causes Purkinje cell degeneration and cerebellar atrophy. Reason: Reflects the requirement for BiP-dependent ER homeostasis for neuronal survival rather than a developmental patterning role; non-core. Supporting Evidence: PMID:19816510 In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator of UPR, is specifically eliminated in Purkinje cells (PCs). PMID:19816510 The mice show retarded growth and severe motor coordination defect by week 5 and cerebellar atrophy by week 13. |
| GO:0021762 substantia nigra development | HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in... | MARK AS OVER ANNOTATED | Summary: Quantitative proteomics of substantia nigra in neurodegenerative disease. Reason: The study measured protein expression changes in diseased adult tissue and does not address a role in substantia nigra development. Supporting Evidence: PMID:22926577 Using a quantitative proteomic approach, we investigated protein expressions in the substantia nigra of Alzheimer's disease, Huntington's disease, and Multiple sclerosis. |
| GO:0030291 protein serine/threonine kinase inhibitor activity | IDA PMID:11907036 Dimerization and release of molecular chaperone inhibition f... | ACCEPT | Summary: BiP binds the luminal domain of PERK in unstressed cells and represses its kinase activation; release upon ER stress allows PERK activation. Reason: Direct repression of a UPR transducer kinase by luminal binding; this is a central regulatory function of BiP in the UPR. Supporting Evidence: PMID:11907036 In the absence of stress, PEK associates with ER chaperones GRP78 (BiP) and GRP94, and this binding is released in response to ER stress. PMID:11907036 These results suggest that this ER chaperone serves as a repressor of PEK activity |
| GO:0030335 positive regulation of cell migration | IMP PMID:23990668 Unraveling the role of KIAA1199, a novel endoplasmic reticul... | KEEP AS NON CORE | Summary: CEMIP/KIAA1199 enhances cell migration through its ER interaction with BiP, causing ER Ca2+ leakage. Reason: Context-specific consequence of a BiP-partner interaction; non-core. Supporting Evidence: PMID:23990668 KIAA1199-enhanced cell migration required endoplasmic reticulum (ER) localization, where it forms a stable complex with the chaperone binding immunoglobulin protein (BiP). |
| GO:0030496 midbody | IDA PMID:15166316 Dissection of the mammalian midbody proteome reveals conserv... | MARK AS OVER ANNOTATED | Summary: High-throughput or proteomic detection associating BiP with midbody. Reason: BiP is among the most abundant ER lumenal proteins and is a frequent co-purifying contaminant in proteomic and interactome studies; this does not establish a function or location in this structure. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0030968 endoplasmic reticulum unfolded protein response | IBA GO_REF:0000033 | ACCEPT | Summary: BiP is the master luminal regulator of the UPR: it binds and represses IRE1, PERK and ATF6 and its release upon misfolded protein accumulation activates the three branches; it is also a major UPR target gene. Reason: Central role in the ER UPR, supported experimentally and by the BiP-branch IBA node. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0030968 endoplasmic reticulum unfolded protein response | IEA GO_REF:0000107 | ACCEPT | Summary: BiP is the master luminal regulator of the UPR: it binds and represses IRE1, PERK and ATF6 and its release upon misfolded protein accumulation activates the three branches; it is also a major UPR target gene. Reason: Central role in the ER UPR, supported experimentally and by the BiP-branch IBA node. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0030968 endoplasmic reticulum unfolded protein response | TAS PMID:19816510 Essential role of the unfolded protein response regulator GR... | ACCEPT | Summary: BiP is the master luminal regulator of the UPR: it binds and represses IRE1, PERK and ATF6 and its release upon misfolded protein accumulation activates the three branches; it is also a major UPR target gene. Reason: Central role in the ER UPR, supported experimentally and by the BiP-branch IBA node. Supporting Evidence: PMID:19816510 In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator of UPR, is specifically eliminated in Purkinje cells (PCs). |
| GO:0031072 heat shock protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Hsp70 family-wide IBA for binding J-domain (Hsp40) co-chaperones. Reason: BiP interacts with multiple ER J-domain proteins (ERdj3/4/5, Sec63) that stimulate its ATPase; correct. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP PMID:12411443 In vitro experiments demonstrated that ERdj5 interacts via its DnaJ domain with BiP in an ATP-dependent manner. |
| GO:0031204 post-translational protein targeting to membrane, translocation | IMP PMID:29719251 Chaperone-Mediated Sec61 Channel Gating during ER Import of ... | ACCEPT | Summary: BiP, with the Sec62/Sec63 complex, facilitates Sec61 channel opening for post-translational import of small presecretory proteins with weak signal peptides. Reason: Directly supported by depletion studies in semipermeabilized human cells; a core ER-lumenal function. Supporting Evidence: PMID:29719251 We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to tran file:human/HSPA5/HSPA5-uniprot.txt Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). |
| GO:0031333 negative regulation of protein-containing complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BiP binding to the luminal domains of IRE1/PERK prevents their stress-induced dimerization/oligomerization. Reason: Accurate mechanistic consequence of BiP binding UPR sensors; captured more specifically by negative regulation of the IRE1/PERK branches. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0031398 positive regulation of protein ubiquitination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation to positive regulation of protein ubiquitination. Reason: Plausible through BiP's role in delivering misfolded clients to ERAD ubiquitination machinery; indirect. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5 |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:8666824 Calreticulin binds hYRNA and the 52-kDa polypeptide componen... | UNDECIDED | Summary: Annotation of ubiquitin protein ligase binding from a calreticulin/Ro52 (TRIM21) paper. Reason: UniProt records an HSPA5-TRIM21 interaction from a different study, but the cited paper's abstract concerns calreticulin and its full text is unavailable here, so the HSPA5-specific evidence could not be verified. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Interacts with TMEM132A and TRIM21 (PubMed:12699405) |
| GO:0032991 protein-containing complex | IDA PMID:23349634 A newly uncovered group of distantly related lysine methyltr... | MARK AS OVER ANNOTATED | Summary: Affinity purification of METTL21-family methyltransferases co-purified chaperones including Hsp70s. Reason: Generic protein-containing complex is uninformative; the specific ER chaperone complex term is already annotated. Supporting Evidence: PMID:23349634 Affinity purification coupled to mass spectrometry shows a marked preference for these proteins to associate with various chaperones. |
| GO:0034663 endoplasmic reticulum chaperone complex | IBA GO_REF:0000033 | ACCEPT | Summary: BiP is a core component of the large ER chaperone multiprotein complex with GRP94, ERdj3, PDIs, GRP170 and others. Reason: Supported by co-purification and the BiP-branch IBA. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0034663 endoplasmic reticulum chaperone complex | IDA PMID:18400946 ERdj4 and ERdj5 are required for endoplasmic reticulum-assoc... | ACCEPT | Summary: BiP is a core component of the large ER chaperone multiprotein complex with GRP94, ERdj3, PDIs, GRP170 and others. Reason: Supported by co-purification and the BiP-branch IBA. Supporting Evidence: PMID:18400946 Immunoglobulin heavy chain binding protein (BiP) and two heat shock protein 40 family members, endoplasmic reticulum-localized DnaJ homologues ERdj4 and ERdj5, were significantly elevated and exhibited prolonged and specific association with the misfolded proprotein file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0034663 endoplasmic reticulum chaperone complex | IEA GO_REF:0000107 | ACCEPT | Summary: BiP is a core component of the large ER chaperone multiprotein complex with GRP94, ERdj3, PDIs, GRP170 and others. Reason: Supported by co-purification and the BiP-branch IBA. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 file:human/HSPA5/HSPA5-uniprot.txt Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 |
| GO:0034975 protein folding in endoplasmic reticulum | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: BiP is a principal folding chaperone of the ER lumen. Reason: Core process. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen PMID:26655470 Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. |
| GO:0034976 response to endoplasmic reticulum stress | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | ACCEPT | Summary: BiP is the master luminal regulator of the UPR: it binds and represses IRE1, PERK and ATF6 and its release upon misfolded protein accumulation activates the three branches; it is also a major UPR target gene. Reason: Central role in the ER UPR, supported experimentally and by the BiP-branch IBA node. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) |
| GO:0035437 maintenance of protein localization in endoplasmic reticulum | IMP PMID:23990668 Unraveling the role of KIAA1199, a novel endoplasmic reticul... | KEEP AS NON CORE | Summary: The ER retention of CEMIP/KIAA1199 depends on an ER-retention motif required for its BiP interaction. Reason: Supported for a specific client; non-core. Supporting Evidence: PMID:23990668 A novel ER-retention motif within KIAA1199 that is required for its ER localization, BiP interaction, and enhanced cell migration was identified. |
| GO:0036498 IRE1-mediated unfolded protein response | IEA GO_REF:0000107 | ACCEPT | Summary: BiP is the master luminal regulator of the UPR: it binds and represses IRE1, PERK and ATF6 and its release upon misfolded protein accumulation activates the three branches; it is also a major UPR target gene. Reason: Central role in the ER UPR, supported experimentally and by the BiP-branch IBA node. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0036503 ERAD quality control pathway | IBA GO_REF:0000033 | ACCEPT | Summary: BiP retains misfolded proteins and, with ERdj4/ERdj5 that stimulate its ATPase, promotes their ER-associated degradation. Reason: Core quality-control function, supported experimentally and by the BiP-branch IBA. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5 PMID:18400946 ERdj4 and ERdj5 promote turnover of misfolded SP-C and this activity is dependent on their ability to stimulate BiP ATPase activity. |
| GO:0036503 ERAD quality control pathway | TAS PMID:19816510 Essential role of the unfolded protein response regulator GR... | ACCEPT | Summary: BiP retains misfolded proteins and, with ERdj4/ERdj5 that stimulate its ATPase, promotes their ER-associated degradation. Reason: Core quality-control function, supported experimentally and by the BiP-branch IBA. Supporting Evidence: PMID:19816510 GRP78-depleted PCs activate UPR including the induction of GRP94, PDI, CHOP and GADD34, feedback suppression of eIF2alpha phosphorylation and apoptotic cell death. |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: Hsp70 family IBA for protein refolding. Reason: BiP refolds and prevents aggregation of ER clients through its ATP-driven cycle. Supporting Evidence: PMID:26655470 Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. file:human/HSPA5/HSPA5-uniprot.txt 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 |
| GO:0042149 cellular response to glucose starvation | IDA PMID:10085239 Transcriptional regulation of the human asparagine synthetas... | KEEP AS NON CORE | Summary: GRP78 mRNA is induced by glucose deprivation and repressed by glucose and certain sugars in HepG2 cells. Reason: Classical glucose-regulated expression response; BiP's participation is as an induced effector of the UPR triggered by glucose starvation. Non-core. Supporting Evidence: PMID:10085239 Fructose, galactose, mannose, 2-deoxyglucose and xylitol were found to maintain the mRNA content of both AS and the glucose-regulated protein GRP78 in a state of repression |
| GO:0042470 melanosome | EXP PMID:12643545 Proteomic analysis of early melanosomes: identification of n... | KEEP AS NON CORE | Summary: Identified by mass spectrometry in melanosome fractions. Reason: Proteomic detection, consistent with ER-derived contamination or transit of an abundant lumenal protein; not functionally core. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Identified by mass spectrometry in melanosome fractions from stage I to stage IV |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Identified by mass spectrometry in melanosome fractions. Reason: Proteomic detection, consistent with ER-derived contamination or transit of an abundant lumenal protein; not functionally core. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Identified by mass spectrometry in melanosome fractions from stage I to stage IV |
| GO:0043022 ribosome binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation of ribosome binding. Reason: BiP acts at the luminal side of the ribosome-Sec61 translocon during import; any ribosome association is likely indirect. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:10760948 Stress protein GRP78 prevents apoptosis induced by calcium i... | KEEP AS NON CORE | Summary: GRP78 overexpression reduces apoptosis, e.g. by blocking caspase-7 activation. Reason: Supported cytoprotective role, largely a consequence of maintaining ER homeostasis and binding caspases; non-core. Supporting Evidence: PMID:10760948 DNA fragmentation assays showed a direct correlation between the onset of apoptosis in LNCaP cells after IM treatment and the initiation of GRP78 transcript induction |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:12665508 Endoplasmic reticulum chaperone protein GRP78 protects cells... | KEEP AS NON CORE | Summary: GRP78 overexpression reduces apoptosis, e.g. by blocking caspase-7 activation. Reason: Supported cytoprotective role, largely a consequence of maintaining ER homeostasis and binding caspases; non-core. Supporting Evidence: PMID:12665508 We show here that specific expression of GRP78 blocks caspase-7 activation by etoposide both in vivo and in vitro |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: GRP78 overexpression reduces apoptosis, e.g. by blocking caspase-7 activation. Reason: Supported cytoprotective role, largely a consequence of maintaining ER homeostasis and binding caspases; non-core. Supporting Evidence: PMID:11943137 GRP78 inhibits cytochrome c-mediated caspase activation in a cell-free system, and expression of GRP78 blocks both caspase activation and caspase-mediated cell death. |
| GO:0043231 intracellular membrane-bounded organelle | IDA PMID:22689054 GRP78 regulates clusterin stability, retrotranslocation and ... | KEEP AS NON CORE | Summary: Generic intracellular membrane-bounded organelle location. Reason: Correct but uninformative; ER lumen is the informative location. Supporting Evidence: PMID:22689054 GRP78 (Bip) associates with CLU under ER stress conditions to facilitate its retrotranslocation and redistribution to the mitochondria. |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | MODIFY | Summary: BiP is the major ER Hsp70 protein-folding chaperone. Reason: BiP is the major ER Hsp70 protein-folding chaperone; the annotation is correct but the ATP-dependent child term describes the Hsp70 mechanism (ATP binding and hydrolysis allosterically controlling substrate binding and release by the SBD), as used for yeast KAR2. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen PMID:26655470 Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. |
| GO:0044183 protein folding chaperone | IEA GO_REF:0000107 | MODIFY | Summary: BiP is the major ER Hsp70 protein-folding chaperone. Reason: BiP is the major ER Hsp70 protein-folding chaperone; the annotation is correct but the ATP-dependent child term describes the Hsp70 mechanism (ATP binding and hydrolysis allosterically controlling substrate binding and release by the SBD), as used for yeast KAR2. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen PMID:26655470 Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. |
| GO:0044183 protein folding chaperone | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | MODIFY | Summary: BiP is the major ER Hsp70 protein-folding chaperone. Reason: BiP is the major ER Hsp70 protein-folding chaperone; the annotation is correct but the ATP-dependent child term describes the Hsp70 mechanism (ATP binding and hydrolysis allosterically controlling substrate binding and release by the SBD), as used for yeast KAR2. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 file:human/HSPA5/HSPA5-uniprot.txt Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen PMID:26655470 Binding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. |
| GO:0044183 protein folding chaperone | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | MODIFY | Summary: BiP is the major ER Hsp70 protein-folding chaperone. Reason: BiP is the major ER Hsp70 protein-folding chaperone; the annotation is correct but the ATP-dependent child term describes the Hsp70 mechanism (ATP binding and hydrolysis allosterically controlling substrate binding and release by the SBD), as used for yeast KAR2. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:26655470 NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. file:human/HSPA5/HSPA5-uniprot.txt 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 PMID:22934019 Key chaperones and folding sensors in the ER include: glucose regulated proteins 78 (GRP78; also known as Immunoglobulin Binding protein β BiP) and 94 (GRP94) |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: High-throughput or proteomic detection associating BiP with cadherin binding. Reason: BiP is among the most abundant ER lumenal proteins and is a frequent co-purifying contaminant in proteomic and interactome studies; this does not establish a function or location in this structure. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0045732 positive regulation of protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation of positive regulation of protein catabolic process. Reason: Consistent with BiP's role in targeting terminally misfolded clients to ERAD; indirect. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | TAS PMID:14685163 Roles of CHOP/GADD153 in endoplasmic reticulum stress. | REMOVE | Summary: TAS from a review on CHOP/GADD153 in ER stress. Reason: HSPA5 is not a transcription regulator; it is a UPR target gene and a luminal repressor of the UPR transducers (ATF6, IRE1, PERK). Its effect on transcription is indirect and already captured by regulation-of-UPR-branch terms. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) |
| GO:0051087 protein-folding chaperone binding | TAS PMID:19816510 Essential role of the unfolded protein response regulator GR... | ACCEPT | Summary: BiP binds co-chaperones (J-domain proteins and nucleotide exchange factors) that regulate its ATPase cycle. Reason: Correct and informative. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt J domain- containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP |
| GO:0051787 misfolded protein binding | IDA PMID:18400946 ERdj4 and ERdj5 are required for endoplasmic reticulum-assoc... | ACCEPT | Summary: BiP binds misfolded clients (e.g. mutant SP-C proprotein) in the ER. Reason: Core client-binding activity in ER quality control. Supporting Evidence: PMID:18400946 Immunoglobulin heavy chain binding protein (BiP) and two heat shock protein 40 family members, endoplasmic reticulum-localized DnaJ homologues ERdj4 and ERdj5, were significantly elevated and exhibited prolonged and specific association with the misfolded proprotein |
| GO:0051787 misfolded protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: BiP binds misfolded clients (e.g. mutant SP-C proprotein) in the ER. Reason: Core client-binding activity in ER quality control. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5 |
| GO:0060904 regulation of protein folding in endoplasmic reticulum | TAS PMID:19816510 Essential role of the unfolded protein response regulator GR... | MODIFY | Summary: TAS (PMID:19816510) for regulation of protein folding in the ER. Reason: BiP directly carries out chaperone-assisted protein folding in the ER rather than regulating it; protein folding in endoplasmic reticulum is the accurate process term. Proposed replacements: protein folding in endoplasmic reticulum Supporting Evidence: PMID:19816510 In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator of UPR, is specifically eliminated in Purkinje cells (PCs). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Detected in urinary exosome proteomics. Reason: High-throughput detection of an abundant ER protein in exosomes; not a functional location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Detected in urinary exosome proteomics. Reason: High-throughput detection of an abundant ER protein in exosomes; not a functional location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Detected in urinary exosome proteomics. Reason: High-throughput detection of an abundant ER protein in exosomes; not a functional location. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0140311 protein sequestering activity | IDA PMID:19538957 Activation of mammalian IRE1alpha upon ER stress depends on ... | ACCEPT | Summary: BiP binds and holds the IRE1alpha luminal domain inactive; IRE1alpha activation depends on BiP dissociation. Reason: Direct evidence that BiP sequesters UPR transducers, a central regulatory function. Supporting Evidence: PMID:19538957 These results suggest that in contrast to yeast Ire1, the regulation of mammalian IRE1alpha strongly depends on the dissociation of BiP. PMID:19538957 We generated a mutant that has low affinity for BiP, and this mutant was significantly activated even under normal conditions. |
| GO:1903891 regulation of ATF6-mediated unfolded protein response | TAS PMID:22934019 The endoplasmic reticulum stress response in aging and age-r... | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: PMID:22934019 Accumulation of misfolded or unfolded proteins in the ER leads to the dissociation of BiP from 3 transducers βPERK, IRE1 and ATF6. |
| GO:1903894 regulation of IRE1-mediated unfolded protein response | IDA PMID:19538957 Activation of mammalian IRE1alpha upon ER stress depends on ... | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: PMID:19538957 We generated a mutant that has low affinity for BiP, and this mutant was significantly activated even under normal conditions. |
| GO:1903894 regulation of IRE1-mediated unfolded protein response | TAS PMID:22934019 The endoplasmic reticulum stress response in aging and age-r... | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: PMID:22934019 Accumulation of misfolded or unfolded proteins in the ER leads to the dissociation of BiP from 3 transducers βPERK, IRE1 and ATF6. |
| GO:1903895 negative regulation of IRE1-mediated unfolded protein response | ISS GO_REF:0000024 | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: file:human/HSPA5/HSPA5-uniprot.txt Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1- mediated unfolded protein response (UPR) |
| GO:1903897 regulation of PERK-mediated unfolded protein response | TAS PMID:22934019 The endoplasmic reticulum stress response in aging and age-r... | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: PMID:22934019 Accumulation of misfolded or unfolded proteins in the ER leads to the dissociation of BiP from 3 transducers βPERK, IRE1 and ATF6. |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | IDA PMID:11907036 Dimerization and release of molecular chaperone inhibition f... | ACCEPT | Summary: BiP regulates the three UPR branches by binding the luminal domains of ATF6, IRE1 and PERK and releasing them upon accumulation of misfolded proteins. Reason: Core regulatory role of BiP in the UPR. Supporting Evidence: PMID:11907036 In the absence of stress, PEK associates with ER chaperones GRP78 (BiP) and GRP94, and this binding is released in response to ER stress. PMID:11907036 These results suggest that this ER chaperone serves as a repressor of PEK activity |
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Download this section (compressed HTML)Q: Does BiP repress IRE1alpha and PERK predominantly as a canonical chaperone-client interaction (substrate-binding domain, ERdj4-dependent) or via a non-canonical nucleotide-binding-domain interaction with the sensor luminal domains, and does this differ between IRE1alpha, PERK and ATF6?
Q: How do FICD-mediated AMPylation and BiP oligomerization partition BiP between active folding and inactive reserve pools in human secretory cells?
Q: Are the cell-surface and cytosolic GRP78 pools produced by a regulated mechanism, and does surface GRP78 have a physiological (non-pathogen) receptor function?
Experiment: Separation-of-function BiP mutants (SBD substrate-binding defective vs NBD-interface mutants) in HSPA5-knockout human cells to measure effects on IRE1/PERK/ATF6 activation versus client folding.
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