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Overview

Uniprot IDP06761
Protein NameEndoplasmic reticulum chaperone BiP
Gene NameHspa5
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
123 PFKVVEKKTKPYIQV
125 KVVEKKTKPYIQVDI
154 AMVLTKMKETAEAYL
163 TAEAYLGKKVTHAVV
164 AEAYLGKKVTHAVVT
185 DAQRQATKDAGTIAG
213 AIAYGLDKREGEKNI
268 RVMEHFIKLYKKKTG
340 DLFRSTMKPVQKVLE
344 STMKPVQKVLEDSDL
352 VLEDSDLKKSDIDEI
353 LEDSDLKKSDIDEIV
370 GGSTRIPKIQQLVKE
446 RNTVVPTKKSQIFST
447 NTVVPTKKSQIFSTA
523 KGTGNKNKITITNDQ
547 RMVNDAEKFAEEDKK
553 EKFAEEDKKLKERID
573 ESYAYSLKNQIGDKE
81 RLIGDAAKNQLTSNP
96 ENTVFDAKRLIGRTW

Function

Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1. Also binds and inactivates EIF2AK3/PERK in unstressed cells. 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 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (By similarity)

Protein Sequence

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

Gene Ontology

Classification GO ID Description
Cellular Component GO:0009986 cell surface
Biological Process GO:0051603 proteolysis involved in protein catabolic process
Biological Process GO:1903894 regulation of IRE1-mediated unfolded protein response
Biological Process GO:0042220 response to cocaine
Biological Process GO:0034976 response to endoplasmic reticulum stress
Biological Process GO:1904313 response to methamphetamine hydrochloride
Biological Process GO:0097501 stress response to metal ion
Cellular Component GO:0008180 COP9 signalosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0043198 dendritic shaft
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:0042470 melanosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0030496 midbody
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0005790 smooth endoplasmic reticulum
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
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:0043022 ribosome binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0051082 unfolded protein binding
Biological Process GO:0071236 cellular response to antibiotic
Biological Process GO:0071277 cellular response to calcium ion
Biological Process GO:0071320 cellular response to cAMP
Biological Process GO:0071480 cellular response to gamma radiation
Biological Process GO:0042149 cellular response to glucose starvation
Biological Process GO:0071353 cellular response to interleukin-4
Biological Process GO:0071287 cellular response to manganese ion
Biological Process GO:1990090 cellular response to nerve growth factor stimulus
Biological Process GO:0071466 cellular response to xenobiotic stimulus
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:0006983 ER overload response
Biological Process GO:0036503 ERAD pathway
Biological Process GO:0036498 IRE1-mediated unfolded protein response
Biological Process GO:0001554 luteolysis
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:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
Biological Process GO:0051402 neuron apoptotic process
Biological Process GO:0030182 neuron differentiation
Biological Process GO:0030335 positive regulation of cell migration
Biological Process GO:0010976 positive regulation of neuron projection development
Biological Process GO:0031398 positive regulation of protein ubiquitination
Biological Process GO:0031204 post-translational protein targeting to membrane, translocation
Biological Process GO:0042026 protein refolding

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.

[2] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.