Search Results
Overview
| Uniprot ID | P11021 |
|---|---|
| Protein Name | Endoplasmic reticulum chaperone BiP |
| Gene Name | HSPA5 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 123 | PFKVVEKKTKPYIQV |
| 125 | KVVEKKTKPYIQVDI |
| 152 | ISAMVLTKMKETAEA |
| 154 | AMVLTKMKETAEAYL |
| 163 | TAEAYLGKKVTHAVV |
| 164 | AEAYLGKKVTHAVVT |
| 185 | DAQRQATKDAGTIAG |
| 213 | AIAYGLDKREGEKNI |
| 268 | RVMEHFIKLYKKKTG |
| 326 | SETLTRAKFEELNMD |
| 340 | DLFRSTMKPVQKVLE |
| 344 | STMKPVQKVLEDSDL |
| 352 | VLEDSDLKKSDIDEI |
| 353 | LEDSDLKKSDIDEIV |
| 370 | GGSTRIPKIQQLVKE |
| 376 | PKIQQLVKEFFNGKE |
| 382 | VKEFFNGKEPSRGIN |
| 446 | RNTVVPTKKSQIFST |
| 447 | NTVVPTKKSQIFSTA |
| 516 | LRVTAEDKGTGNKNK |
| 523 | KGTGNKNKITITNDQ |
| 547 | RMVNDAEKFAEEDKK |
| 553 | EKFAEEDKKLKERID |
| 573 | ESYAYSLKNQIGDKE |
| 579 | LKNQIGDKEKLGGKL |
| 601 | MEKAVEEKIEWLESH |
| 81 | RLIGDAAKNQLTSNP |
| 96 | ENTVFDAKRLIGRTW |
Function
Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:11907036, PubMed:1550958, PubMed:19538957, PubMed:36739529). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Also binds and inactivates EIF2AK3/PERK in unstressed cells (PubMed:11907036). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerization and subsequent activation (PubMed:11907036). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0009986 | cell surface |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0034663 | endoplasmic reticulum chaperone complex |
| Cellular Component | GO:0005788 | endoplasmic reticulum lumen |
| Cellular Component | GO:0005789 | endoplasmic reticulum membrane |
| Cellular Component | GO:0005793 | endoplasmic reticulum-Golgi intermediate compartment |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005925 | focal adhesion |
| Cellular Component | GO:0043231 | intracellular membrane-bounded organelle |
| Cellular Component | GO:0042470 | melanosome |
| Cellular Component | GO:0016020 | membrane |
| Cellular Component | GO:0030496 | midbody |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0032991 | protein-containing complex |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0016887 | ATP hydrolysis activity |
| Molecular Function | GO:0045296 | cadherin binding |
| Molecular Function | GO:0005509 | calcium ion binding |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:0031072 | heat shock protein binding |
| Molecular Function | GO:0051787 | misfolded protein binding |
| Molecular Function | GO:0019904 | protein domain specific binding |
| Molecular Function | GO:0044183 | protein folding chaperone |
| Molecular Function | GO:0140311 | protein sequestering activity |
| Molecular Function | GO:0030291 | protein serine/threonine kinase inhibitor activity |
| Molecular Function | GO:0051087 | protein-folding chaperone binding |
| Molecular Function | GO:0043022 | ribosome binding |
| Molecular Function | GO:0031625 | ubiquitin protein ligase binding |
| Molecular Function | GO:0051082 | unfolded protein binding |
| Biological Process | GO:0042149 | cellular response to glucose starvation |
| Biological Process | GO:0021680 | cerebellar Purkinje cell layer development |
| Biological Process | GO:0021589 | cerebellum structural organization |
| Biological Process | GO:0030968 | endoplasmic reticulum unfolded protein response |
| Biological Process | GO:0036503 | ERAD pathway |
| Biological Process | GO:0036498 | IRE1-mediated unfolded protein response |
| Biological Process | GO:0035437 | maintenance of protein localization in endoplasmic reticulum |
| Biological Process | GO:0043066 | negative regulation of apoptotic process |
| Biological Process | GO:1903895 | negative regulation of IRE1-mediated unfolded protein response |
| Biological Process | GO:1903898 | negative regulation of PERK-mediated unfolded protein response |
| Biological Process | GO:0031333 | negative regulation of protein-containing complex assembly |
| Biological Process | GO:0030335 | positive regulation of cell migration |
| Biological Process | GO:0031398 | positive regulation of protein ubiquitination |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0031204 | post-translational protein targeting to membrane, translocation |
| Biological Process | GO:0034975 | protein folding in endoplasmic reticulum |
| Biological Process | GO:0042026 | protein refolding |
| Biological Process | GO:1903891 | regulation of ATF6-mediated unfolded protein response |
| Biological Process | GO:1903894 | regulation of IRE1-mediated unfolded protein response |
| Biological Process | GO:1903897 | regulation of PERK-mediated unfolded protein response |
| Biological Process | GO:0060904 | regulation of protein folding in endoplasmic reticulum |
| Biological Process | GO:0034976 | response to endoplasmic reticulum stress |
| Biological Process | GO:0021762 | substantia nigra development |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.