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Overview

Uniprot IDP04785
Protein NameProtein disulfide-isomerase
Gene NameP4hb
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
116 NGDTASPKEYTAGRE
132 DDIVNWLKKRTGPAA
202 FSKYQLDKDGVVLFK
224 NFEGEITKEKLLDFI
226 EGEITKEKLLDFIKH
273 SVSDYDGKLSNFKKA
310 ILEFFGLKKEECPAV
311 LEFFGLKKEECPAVR
328 TLEEEMTKYKPESDE
330 EEEMTKYKPESDELT
354 HFLEGKIKPHLMSQE
372 DWDKQPVKVLVGKNF
377 PVKVLVGKNFEEVAF
387 EEVAFDEKKNVFVEF
426 HENIVIAKMDSTANE
446 VHSFPTLKFFPASAD
469 ERTLDGFKKFLESGG
67 ALAPEYAKAAAKLKA
73 AKAAAKLKAEGSEIR
83 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. 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

Protein Sequence

10 MLSRALLCLA 20 LAWAARVGAD 30 ALEEEDNVLV 40 LKKSNFAEAL 50 AAHNYLLVEF 60 YAPWCGHCKA 70 LAPEYAKAAA 80 KLKAEGSEIR 90 LAKVDATEES 100 DLAQQYGVRG 110 YPTIKFFKNG 120 DTASPKEYTA 130 GREADDIVNW 140 LKKRTGPAAT 150 TLSDTAAAES 160 LVDSSEVTVI 170 GFFKDAGSDS 180 AKQFLLAAEA 190 VDDIPFGITS 200 NSDVFSKYQL 210 DKDGVVLFKK 220 FDEGRNNFEG 230 EITKEKLLDF 240 IKHNQLPLVI 250 EFTEQTAPKI 260 FGGEIKTHIL 270 LFLPKSVSDY 280 DGKLSNFKKA 290 AEGFKGKILF 300 IFIDSDHTDN 310 QRILEFFGLK 320 KEECPAVRLI 330 TLEEEMTKYK 340 PESDELTAEK 350 ITQFCHHFLE 360 GKIKPHLMSQ 370 ELPEDWDKQP 380 VKVLVGKNFE 390 EVAFDEKKNV 400 FVEFYAPWCG 410 HCKQLAPIWD 420 KLGETYKDHE 430 NIVIAKMDST 440 ANEVEAVKVH 450 SFPTLKFFPA 460 SADRTVIDYN 470 GERTLDGFKK 480 FLESGGQDGA 490 GDNDDLDLEE 500 ALEPDMEEDD DQKAVKDEL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005856 cytoskeleton
Cellular Component GO:0005829 cytosol
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: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:0044877 protein-containing complex binding
Molecular Function GO:0015035 protein-disulfide reductase activity
Molecular Function GO:0016972 thiol oxidase activity
Biological Process GO:0071456 cellular response to hypoxia
Biological Process GO:0098761 cellular response to interleukin-7
Biological Process GO:0030070 insulin processing
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] 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.