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Overview

Uniprot IDP07237
Protein NameProtein disulfide-isomerase
Gene NameP4HB
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
103 VRGYPTIKFFRNGDT
114 NGDTASPKEYTAGRE
130 DDIVNWLKKRTGPAA
200 FSKYQLDKDGVVLFK
207 KDGVVLFKKFDEGRN
208 DGVVLFKKFDEGRNN
247 FTEQTAPKIFGGEIK
263 HILLFLPKSVSDYDG
271 SVSDYDGKLSNFKTA
276 DGKLSNFKTAAESFK
283 KTAAESFKGKILFIF
308 ILEFFGLKKEECPAV
309 LEFFGLKKEECPAVR
31 DHVLVLRKSNFAEAL
326 TLEEEMTKYKPESEE
328 EEEMTKYKPESEELT
350 CHRFLEGKIKPHLMS
352 RFLEGKIKPHLMSQE
370 DWDKQPVKVLVGKNF
375 PVKVLVGKNFEDVAF
385 EDVAFDEKKNVFVEF
386 DVAFDEKKNVFVEFY
409 QLAPIWDKLGETYKD
436 ANEVEAVKVHSFPTL
444 VHSFPTLKFFPASAD
467 ERTLDGFKKFLESGG
65 ALAPEYAKAAGKLKA
71 AKAAGKLKAEGSEIR
81 GSEIRLAKVDATEES

Function

This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307)

Protein Sequence

10 MLRRALLCLA 20 VAALVRADAP 30 EEEDHVLVLR 40 KSNFAEALAA 50 HKYLLVEFYA 60 PWCGHCKALA 70 PEYAKAAGKL 80 KAEGSEIRLA 90 KVDATEESDL 100 AQQYGVRGYP 110 TIKFFRNGDT 120 ASPKEYTAGR 130 EADDIVNWLK 140 KRTGPAATTL 150 PDGAAAESLV 160 ESSEVAVIGF 170 FKDVESDSAK 180 QFLQAAEAID 190 DIPFGITSNS 200 DVFSKYQLDK 210 DGVVLFKKFD 220 EGRNNFEGEV 230 TKENLLDFIK 240 HNQLPLVIEF 250 TEQTAPKIFG 260 GEIKTHILLF 270 LPKSVSDYDG 280 KLSNFKTAAE 290 SFKGKILFIF 300 IDSDHTDNQR 310 ILEFFGLKKE 320 ECPAVRLITL 330 EEEMTKYKPE 340 SEELTAERIT 350 EFCHRFLEGK 360 IKPHLMSQEL 370 PEDWDKQPVK 380 VLVGKNFEDV 390 AFDEKKNVFV 400 EFYAPWCGHC 410 KQLAPIWDKL 420 GETYKDHENI 430 VIAKMDSTAN 440 EVEAVKVHSF 450 PTLKFFPASA 460 DRTVIDYNGE 470 RTLDGFKKFL 480 ESGGQDGAGD 490 DDDLEDLEEA 500 EEPDMEEDDD QKAVKDEL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005856 cytoskeleton
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:0005793 endoplasmic reticulum-Golgi intermediate compartment
Cellular Component GO:0009897 external side of plasma membrane
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005576 extracellular region
Cellular Component GO:0005925 focal adhesion
Cellular Component GO:0030027 lamellipodium
Cellular Component GO:0042470 melanosome
Cellular Component GO:0016222 procollagen-proline 4-dioxygenase complex
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0003779 actin binding
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0005178 integrin binding
Molecular Function GO:0004656 procollagen-proline 4-dioxygenase activity
Molecular Function GO:0003756 protein disulfide isomerase activity
Molecular Function GO:0046982 protein heterodimerization activity
Molecular Function GO:0015035 protein-disulfide reductase activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0016972 thiol oxidase activity
Biological Process GO:0071456 cellular response to hypoxia
Biological Process GO:0030070 insulin processing
Biological Process GO:0035722 interleukin-12-mediated signaling pathway
Biological Process GO:0038155 interleukin-23-mediated signaling pathway
Biological Process GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline
Biological Process GO:0045785 positive regulation of cell adhesion
Biological Process GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
Biological Process GO:2000406 positive regulation of T cell migration
Biological Process GO:0046598 positive regulation of viral entry into host cell
Biological Process GO:0006457 protein folding
Biological Process GO:0034975 protein folding in endoplasmic reticulum
Biological Process GO:1902175 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
Biological Process GO:0034976 response to endoplasmic reticulum stress

Reference

[1] 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.

[2] 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.

[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[5] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[6] 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.

[7] 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.

[8] 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.