ID PDIA1_HUMAN Reviewed; 508 AA. AC P07237; B2RDQ2; P30037; P32079; Q15205; Q6LDE5; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 3. DT 05-FEB-2025, entry version 275. DE RecName: Full=Protein disulfide-isomerase; DE Short=PDI; DE EC=5.3.4.1 {ECO:0000269|PubMed:32149426}; DE AltName: Full=Cellular thyroid hormone-binding protein; DE AltName: Full=Prolyl 4-hydroxylase subunit beta; DE AltName: Full=p55; DE Flags: Precursor; GN Name=P4HB; Synonyms=ERBA2L, PDI, PDIA1, PO4DB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3034602; DOI=10.1002/j.1460-2075.1987.tb04803.x; RA Pihlajaniemi T., Helaakoski T., Tasanen K., Myllylae R., Huhtala M.-L., RA Koivu J., Kivirikko K.I.; RT "Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This RT subunit and protein disulphide isomerase are products of the same gene."; RL EMBO J. 6:643-649(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3611107; DOI=10.1016/s0021-9258(18)60947-0; RA Cheng S.-Y., Gong Q.-H., Parkison C., Robinson E.A., Appella E., RA Merlino G.T., Pastan I.; RT "The nucleotide sequence of a human cellular thyroid hormone binding RT protein present in endoplasmic reticulum."; RL J. Biol. Chem. 262:11221-11227(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX PubMed=2846539; DOI=10.1016/s0021-9258(18)37581-1; RA Tasanen K., Parkkonen T., Chow L.T., Kivirikko K.I., Pihlajaniemi T.; RT "Characterization of the human gene for a polypeptide that acts both as the RT beta subunit of prolyl 4-hydroxylase and as protein disulfide isomerase."; RL J. Biol. Chem. 263:16218-16224(1988). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon, Lung, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. RX PubMed=1597478; DOI=10.1016/s0021-9258(19)49940-7; RA Tasanen K., Oikarinen J., Kivirikko K.I., Pihlajaniemi T.; RT "Promoter of the gene for the multifunctional protein disulfide isomerase RT polypeptide. Functional significance of the six CCAAT boxes and other RT promoter elements."; RL J. Biol. Chem. 267:11513-11519(1992). RN [8] RP PROTEIN SEQUENCE OF 18-41. RC TISSUE=Colon carcinoma; RX PubMed=9150948; DOI=10.1002/elps.1150180344; RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.; RT "A two-dimensional gel database of human colon carcinoma proteins."; RL Electrophoresis 18:605-613(1997). RN [9] RP PROTEIN SEQUENCE OF 18-30. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [10] RP PROTEIN SEQUENCE OF 18-29. RC TISSUE=Liver; RA Frutiger S., Hughes G.J.; RL Submitted (FEB-1996) to UniProtKB. RN [11] RP PROTEIN SEQUENCE OF 18-26. RX PubMed=2079031; DOI=10.1002/elps.1150111019; RA Ward L.D., Hong J., Whitehead R.H., Simpson R.J.; RT "Development of a database of amino acid sequences for human colon RT carcinoma proteins separated by two-dimensional polyacrylamide gel RT electrophoresis."; RL Electrophoresis 11:883-891(1990). RN [12] RP PRELIMINARY PROTEIN SEQUENCE OF 19-28. RC TISSUE=Liver; RX PubMed=1286669; DOI=10.1002/elps.11501301201; RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., RA Appel R.D., Hughes G.J.; RT "Human liver protein map: a reference database established by RT microsequencing and gel comparison."; RL Electrophoresis 13:992-1001(1992). RN [13] RP PROTEIN SEQUENCE OF 19-28. RX PubMed=9399589; DOI=10.1093/oxfordjournals.jbchem.a021830; RA Urade R., Oda T., Ito H., Moriyama T., Utsumi S., Kito M.; RT "Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu RT (QEDL) motifs of microsomal ER-60 protease."; RL J. Biochem. 122:834-842(1997). RN [14] RP PROTEIN SEQUENCE OF 201-207; 223-230; 286-308 AND 402-409, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 293-508. RX PubMed=3342239; DOI=10.1016/0167-4781(88)90080-2; RA Morris J.I., Varandani P.T.; RT "Characterization of a cDNA for human glutathione-insulin transhydrogenase RT (protein-disulfide isomerase/oxidoreductase)."; RL Biochim. Biophys. Acta 949:169-180(1988). RN [16] RP PROTEIN SEQUENCE OF 317-325; 350-369 AND 401-419. RX PubMed=1699755; DOI=10.1002/elps.1150110703; RA Bauw G., Rasmussen H.H., van den Bulcke M., van Damme J., Puype M., RA Gesser B., Celis J.E., Vandekerckhove J.; RT "Two-dimensional gel electrophoresis, protein electroblotting and RT microsequencing: a direct link between proteins and genes."; RL Electrophoresis 11:528-536(1990). RN [17] RP INTERACTION WITH P4HA2. RX PubMed=7753822; DOI=10.1073/pnas.92.10.4427; RA Helaakoski T., Annunen P., Vuori K., Macneil I.A., Pihlajaniemi T., RA Kivirikko K.I.; RT "Cloning, baculovirus expression, and characterization of a second mouse RT prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2 RT tetramer with the protein disulfide-isomerase/beta subunit."; RL Proc. Natl. Acad. Sci. U.S.A. 92:4427-4431(1995). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10636893; DOI=10.1074/jbc.275.3.1920; RA Mezghrani A., Courageot J., Mani J.-C., Pugniere M., Bastiani P., RA Miquelis R.; RT "Protein-disulfide isomerase (PDI) in FRTL5 cells. pH-dependent RT thyroglobulin/PDI interactions determine a novel PDI function in the post- RT endoplasmic reticulum of thyrocytes."; RL J. Biol. Chem. 275:1920-1929(2000). RN [19] RP INTERACTION WITH ERO1B. RX PubMed=11707400; DOI=10.1093/emboj/20.22.6288; RA Mezghrani A., Fassio A., Benham A., Simmen T., Braakman I., Sitia R.; RT "Manipulation of oxidative protein folding and PDI redox state in mammalian RT cells."; RL EMBO J. 20:6288-6296(2001). RN [20] RP REDUCTION OF HIV-1 SURFACE PROTEIN GP120 DISULFIDE BONDS, AND SUBCELLULAR RP LOCATION. RX PubMed=11181151; DOI=10.1086/318823; RA Fenouillet E., Barbouche R., Courageot J., Miquelis R.; RT "The catalytic activity of protein disulfide isomerase is involved in human RT immunodeficiency virus envelope-mediated membrane fusion after CD4 cell RT binding."; RL J. Infect. Dis. 183:744-752(2001). RN [21] RP FUNCTION. RX PubMed=12485997; DOI=10.1093/emboj/cdf685; RA Lumb R.A., Bulleid N.J.; RT "Is protein disulfide isomerase a redox-dependent molecular chaperone?"; RL EMBO J. 21:6763-6770(2002). RN [22] RP INTERACTION WITH UBQLN1. RX PubMed=12095988; DOI=10.1074/jbc.m203412200; RA Ko H.S., Uehara T., Nomura Y.; RT "Role of ubiquilin associated with protein-disulfide isomerase in the RT endoplasmic reticulum in stress-induced apoptotic cell death."; RL J. Biol. Chem. 277:35386-35392(2002). RN [23] RP REDUCTION OF HIV-1 SURFACE PROTEIN GP120 DISULFIDE BONDS. RX PubMed=12218051; DOI=10.1074/jbc.m204547200; RA Gallina A., Hanley T.M., Mandel R., Trahey M., Broder C.C., Viglianti G.A., RA Ryser H.J.; RT "Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide RT bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry."; RL J. Biol. Chem. 277:50579-50588(2002). RN [24] RP REDUCTION OF HIV-1 SURFACE PROTEIN GP120 DISULFIDE BONDS. RX PubMed=12218052; DOI=10.1074/jbc.m205467200; RA Barbouche R., Miquelis R., Jones I.M., Fenouillet E.; RT "Protein-disulfide isomerase-mediated reduction of two disulfide bonds of RT HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for RT fusion."; RL J. Biol. Chem. 278:3131-3136(2003). RN [25] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [26] RP REVIEW. RX PubMed=15158710; DOI=10.1016/j.bbapap.2004.02.017; RA Wilkinson B., Gilbert H.F.; RT "Protein disulfide isomerase."; RL Biochim. Biophys. Acta 1699:35-44(2004). RN [27] RP REDUCTION OF HIV-1 SURFACE PROTEIN GP120 DISULFIDE BONDS. RX PubMed=14592831; DOI=10.1182/blood-2003-05-1390; RA Markovic I., Stantchev T.S., Fields K.H., Tiffany L.J., Tomic M., RA Weiss C.D., Broder C.C., Strebel K., Clouse K.A.; RT "Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 RT envelope-mediated T-cell fusion during viral entry."; RL Blood 103:1586-1594(2004). RN [28] RP REDUCTION OF HIV-1 SURFACE PROTEIN GP120 DISULFIDE BONDS. RX PubMed=15644496; DOI=10.1124/mol.104.008276; RA Barbouche R., Lortat-Jacob H., Jones I.M., Fenouillet E.; RT "Glycosaminoglycans and protein disulfide isomerase-mediated reduction of RT HIV Env."; RL Mol. Pharmacol. 67:1111-1118(2005). RN [29] RP INTERACTION WITH MTTP. RX PubMed=16478722; DOI=10.1074/jbc.m512823200; RA Rava P., Ojakian G.K., Shelness G.S., Hussain M.M.; RT "Phospholipid transfer activity of microsomal triacylglycerol transfer RT protein is sufficient for the assembly and secretion of apolipoprotein B RT lipoproteins."; RL J. Biol. Chem. 281:11019-11027(2006). RN [30] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION AS RECEPTOR FOR LGALS9, AND RP SUBCELLULAR LOCATION. RX PubMed=21670307; DOI=10.1073/pnas.1017954108; RA Bi S., Hong P.W., Lee B., Baum L.G.; RT "Galectin-9 binding to cell surface protein disulfide isomerase regulates RT the redox environment to enhance T-cell migration and HIV entry."; RL Proc. Natl. Acad. Sci. U.S.A. 108:10650-10655(2011). RN [33] RP INTERACTION WITH MTTP, AND SUBCELLULAR LOCATION. RX PubMed=23475612; DOI=10.1194/jlr.m031658; RA Khatun I., Walsh M.T., Hussain M.M.; RT "Loss of both phospholipid and triglyceride transfer activities of RT microsomal triglyceride transfer protein in abetalipoproteinemia."; RL J. Lipid Res. 54:1541-1549(2013). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [35] RP PHOSPHORYLATION AT SER-357. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [36] RP INVOLVEMENT IN CLCRP1, VARIANT CLCRP1 CYS-393, AND CHARACTERIZATION OF RP VARIANT CLCRP1 CYS-393. RX PubMed=25683117; DOI=10.1016/j.ajhg.2014.12.027; RA Rauch F., Fahiminiya S., Majewski J., Carrot-Zhang J., Boudko S., RA Glorieux F., Mort J.S., Baechinger H.P., Moffatt P.; RT "Cole-Carpenter syndrome is caused by a heterozygous missense mutation in RT P4HB."; RL Am. J. Hum. Genet. 96:425-431(2015). RN [37] RP INTERACTION WITH MTTP. RX PubMed=26224785; DOI=10.1161/circgenetics.115.001106; RA Walsh M.T., Iqbal J., Josekutty J., Soh J., Di Leo E., Oezaydin E., RA Guenduez M., Tarugi P., Hussain M.M.; RT "A novel abetalipoproteinemia missense mutation highlights the importance RT of N-Terminal beta-barrel in microsomal triglyceride transfer protein RT function."; RL Circ. Cardiovasc. Genet. 8:677-687(2015). RN [38] RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-17, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [39] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ERN1, SUBCELLULAR LOCATION, RP PHOSPHORYLATION AT SER-331; SER-357 AND SER-427, AND MUTAGENESIS OF RP TRP-128; SER-331; SER-357; LEU-403 AND SER-427. RX PubMed=32149426; DOI=10.15252/embj.2019103841; RA Yu J., Li T., Liu Y., Wang X., Zhang J., Wang X., Shi G., Lou J., Wang L., RA Wang C.C., Wang L.; RT "Phosphorylation switches protein disulfide isomerase activity to maintain RT proteostasis and attenuate ER stress."; RL EMBO J. 39:e103841-e103841(2020). RN [40] RP STRUCTURE BY NMR OF 18-137. RX PubMed=8580850; DOI=10.1002/pro.5560041216; RA Kemmink J., Darby N.J., Dijkstra K., Scheek R.M., Creighton T.E.; RT "Nuclear magnetic resonance characterization of the N-terminal thioredoxin- RT like domain of protein disulfide isomerase."; RL Protein Sci. 4:2587-2593(1995). RN [41] RP STRUCTURE BY NMR OF 18-137, AND DISULFIDE BOND. RX PubMed=8672469; DOI=10.1021/bi960335m; RA Kemmink J., Darby N.J., Dijkstra K., Nilges M., Creighton T.E.; RT "Structure determination of the N-terminal thioredoxin-like domain of RT protein disulfide isomerase using multidimensional heteronuclear 13C/15N RT NMR spectroscopy."; RL Biochemistry 35:7684-7691(1996). RN [42] RP STRUCTURE BY NMR OF 136-245. RX PubMed=10383197; DOI=10.1023/a:1008341820489; RA Kemmink J., Dijkstra K., Mariani M., Scheek R.M., Penka E., Nilges M., RA Darby N.J.; RT "The structure in solution of the B domain of protein disulfide RT isomerase."; RL J. Biomol. NMR 13:357-368(1999). RN [43] RP STRUCTURE BY NMR OF 368-477. RG RIKEN structural genomics initiative (RSGI); RT "The solution structure of the second thioredoxin-like domain of human RT protein disulfide-isomerase."; RL Submitted (NOV-2005) to the PDB data bank. CC -!- FUNCTION: This multifunctional protein catalyzes the formation, CC breakage and rearrangement of disulfide bonds. At the cell surface, CC seems to act as a reductase that cleaves disulfide bonds of proteins CC attached to the cell. May therefore cause structural modifications of CC exofacial proteins. Inside the cell, seems to form/rearrange disulfide CC bonds of nascent proteins. At high concentrations and following CC phosphorylation by FAM20C, functions as a chaperone that inhibits CC aggregation of misfolded proteins (PubMed:32149426). At low CC concentrations, facilitates aggregation (anti-chaperone activity). May CC be involved with other chaperones in the structural modification of the CC TG precursor in hormone biogenesis. Also acts as a structural subunit CC of various enzymes such as prolyl 4-hydroxylase and microsomal CC triacylglycerol transfer protein MTTP. Receptor for LGALS9; the CC interaction retains P4HB at the cell surface of Th2 T helper cells, CC increasing disulfide reductase activity at the plasma membrane, CC altering the plasma membrane redox state and enhancing cell migration CC (PubMed:21670307). {ECO:0000269|PubMed:10636893, CC ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, CC ECO:0000269|PubMed:32149426}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.; CC EC=5.3.4.1; Evidence={ECO:0000269|PubMed:32149426}; CC -!- SUBUNIT: Heterodimer; heterodimerizes with the protein microsomal CC triglyceride transfer MTTP (PubMed:16478722, PubMed:23475612, CC PubMed:26224785). Homodimer. Monomers and homotetramers may also occur. CC Interacts with P4HA2, forming a heterotetramer consisting of 2 alpha CC subunits (P4HA2) and 2 beta (P4HB), where P4HB plays the role of a CC structural subunit; this tetramer catalyzes the formation of 4- CC hydroxyproline in collagen (PubMed:7753822). Also constitutes the CC structural subunit of the microsomal triacylglycerol transfer protein CC MTTP in mammalian cells. Stabilizes both enzymes and retain them in the CC ER without contributing to the catalytic activity (By similarity). CC Binds UBQLN1 (PubMed:12095988). Interacts with ERO1B (PubMed:11707400). CC Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a CC P4HB/PDI-CD4-CXCR4-gp120 complex. Interacts with ILDR2 (By similarity). CC Interacts with ERN1/IRE1A (via N-terminus); the interaction is enhanced CC by phosphorylation of P4HB by FAM20C in response to endoplasmic CC reticulum stress and results in attenuation of ERN1 activity CC (PubMed:32149426). {ECO:0000250, ECO:0000250|UniProtKB:P09103, CC ECO:0000269|PubMed:11707400, ECO:0000269|PubMed:12095988, CC ECO:0000269|PubMed:16478722, ECO:0000269|PubMed:23475612, CC ECO:0000269|PubMed:26224785, ECO:0000269|PubMed:32149426, CC ECO:0000269|PubMed:7753822}. CC -!- INTERACTION: CC P07237; Q9NU02: ANKEF1; NbExp=3; IntAct=EBI-395883, EBI-8464238; CC P07237; Q96RK4: BBS4; NbExp=3; IntAct=EBI-395883, EBI-1805814; CC P07237; O43521: BCL2L11; NbExp=3; IntAct=EBI-395883, EBI-526406; CC P07237; P17655: CAPN2; NbExp=3; IntAct=EBI-395883, EBI-1028956; CC P07237; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-395883, EBI-742887; CC P07237; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-395883, EBI-11953200; CC P07237; Q9Y6H1: CHCHD2; NbExp=3; IntAct=EBI-395883, EBI-2321769; CC P07237; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-395883, EBI-741032; CC P07237; P09228: CST2; NbExp=3; IntAct=EBI-395883, EBI-8832659; CC P07237; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-395883, EBI-742054; CC P07237; Q96HE7: ERO1A; NbExp=2; IntAct=EBI-395883, EBI-2564539; CC P07237; Q53R41: FASTKD1; NbExp=3; IntAct=EBI-395883, EBI-3957005; CC P07237; Q9ULW2: FZD10; NbExp=3; IntAct=EBI-395883, EBI-8803802; CC P07237; Q8NEG0: GARIN6; NbExp=3; IntAct=EBI-395883, EBI-752049; CC P07237; P62873: GNB1; NbExp=3; IntAct=EBI-395883, EBI-357130; CC P07237; P28799: GRN; NbExp=4; IntAct=EBI-395883, EBI-747754; CC P07237; Q8TCT9: HM13; NbExp=3; IntAct=EBI-395883, EBI-347472; CC P07237; Q8N4N3-2: KLHL36; NbExp=3; IntAct=EBI-395883, EBI-10973851; CC P07237; Q9P2K6: KLHL42; NbExp=3; IntAct=EBI-395883, EBI-739890; CC P07237; P02538: KRT6A; NbExp=3; IntAct=EBI-395883, EBI-702198; CC P07237; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-395883, EBI-11953334; CC P07237; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-395883, EBI-11953846; CC P07237; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-395883, EBI-10302392; CC P07237; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-395883, EBI-3958099; CC P07237; Q3LI67: KRTAP6-3; NbExp=3; IntAct=EBI-395883, EBI-22311199; CC P07237; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-395883, EBI-11958364; CC P07237; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-395883, EBI-10245913; CC P07237; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-395883, EBI-10246750; CC P07237; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-395883, EBI-10246358; CC P07237; P80188: LCN2; NbExp=3; IntAct=EBI-395883, EBI-11911016; CC P07237; Q6PJG9: LRFN4; NbExp=3; IntAct=EBI-395883, EBI-7910762; CC P07237; P10636-8: MAPT; NbExp=6; IntAct=EBI-395883, EBI-366233; CC P07237; Q92692-2: NECTIN2; NbExp=3; IntAct=EBI-395883, EBI-6979889; CC P07237; O94818-2: NOL4; NbExp=3; IntAct=EBI-395883, EBI-10190763; CC P07237; Q9P121-3: NTM; NbExp=3; IntAct=EBI-395883, EBI-12027160; CC P07237; Q14990: ODF1; NbExp=3; IntAct=EBI-395883, EBI-10234557; CC P07237; O15460: P4HA2; NbExp=3; IntAct=EBI-395883, EBI-348033; CC P07237; O15534: PER1; NbExp=3; IntAct=EBI-395883, EBI-2557276; CC P07237; Q63HM9: PLCXD3; NbExp=3; IntAct=EBI-395883, EBI-12105500; CC P07237; O00444: PLK4; NbExp=3; IntAct=EBI-395883, EBI-746202; CC P07237; Q13162: PRDX4; NbExp=2; IntAct=EBI-395883, EBI-2211957; CC P07237; Q09028: RBBP4; NbExp=3; IntAct=EBI-395883, EBI-620823; CC P07237; Q96B97: SH3KBP1; NbExp=3; IntAct=EBI-395883, EBI-346595; CC P07237; Q86WV1-2: SKAP1; NbExp=3; IntAct=EBI-395883, EBI-11995314; CC P07237; Q8WUG5: SLC22A17; NbExp=3; IntAct=EBI-395883, EBI-11722858; CC P07237; Q03518: TAP1; NbExp=4; IntAct=EBI-395883, EBI-747259; CC P07237; Q5T0J7-2: TEX35; NbExp=3; IntAct=EBI-395883, EBI-12833746; CC P07237; P01137: TGFB1; NbExp=3; IntAct=EBI-395883, EBI-779636; CC P07237; Q9UC07-2: ZNF69; NbExp=3; IntAct=EBI-395883, EBI-12310821; CC P07237; Q2GL86: APH_0248; Xeno; NbExp=3; IntAct=EBI-395883, EBI-26435798; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:32149426}. Endoplasmic CC reticulum lumen {ECO:0000269|PubMed:10636893, CC ECO:0000269|PubMed:23475612}. Melanosome {ECO:0000269|PubMed:12643545, CC ECO:0000269|PubMed:17081065}. Cell membrane CC {ECO:0000269|PubMed:21670307}; Peripheral membrane protein CC {ECO:0000305}. Note=Highly abundant. In some cell types, seems to be CC also secreted or associated with the plasma membrane, where it CC undergoes constant shedding and replacement from intracellular sources CC (Probable). Localizes near CD4-enriched regions on lymphoid cell CC surfaces (PubMed:11181151). Identified by mass spectrometry in CC melanosome fractions from stage I to stage IV (PubMed:10636893). CC Colocalizes with MTTP in the endoplasmic reticulum (PubMed:23475612). CC {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:11181151, CC ECO:0000269|PubMed:23475612, ECO:0000305}. CC -!- PTM: Phosphorylation of Ser-357 by FAM20C is induced by endoplasmic CC reticulum stress and results in a functional switch from oxidoreductase CC to molecular chaperone (PubMed:32149426). It also promotes interaction CC with ERN1 (PubMed:32149426). {ECO:0000269|PubMed:32149426}. CC -!- DISEASE: Cole-Carpenter syndrome 1 (CLCRP1) [MIM:112240]: A form of CC Cole-Carpenter syndrome, a disorder characterized by features of CC osteogenesis imperfecta such as bone deformities and severe bone CC fragility with frequent fractures, in association with CC craniosynostosis, ocular proptosis, hydrocephalus, growth failure and CC distinctive facial features. Craniofacial findings include marked CC frontal bossing, midface hypoplasia, and micrognathia. Despite the CC craniosynostosis and hydrocephalus, intellectual development is normal. CC CLCRP1 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:25683117}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Reduces and may activate fusogenic properties of HIV-1 CC gp120 surface protein, thereby enabling HIV-1 entry into the cell. CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X05130; CAA28775.1; -; mRNA. DR EMBL; J02783; AAA61169.1; -; mRNA. DR EMBL; M22806; AAC13652.1; -; Genomic_DNA. DR EMBL; M22803; AAC13652.1; JOINED; Genomic_DNA. DR EMBL; M22804; AAC13652.1; JOINED; Genomic_DNA. DR EMBL; M22805; AAC13652.1; JOINED; Genomic_DNA. DR EMBL; AK315631; BAG37999.1; -; mRNA. DR EMBL; CH471099; EAW89690.1; -; Genomic_DNA. DR EMBL; BC010859; AAH10859.1; -; mRNA. DR EMBL; BC029617; AAH29617.1; -; mRNA. DR EMBL; BC071892; AAH71892.1; -; mRNA. DR EMBL; S37207; AAB22262.2; -; Genomic_DNA. DR EMBL; X07077; CAA30112.1; -; mRNA. DR CCDS; CCDS11787.1; -. DR PIR; A31913; ISHUSS. DR RefSeq; NP_000909.2; NM_000918.3. DR PDB; 1BJX; NMR; -; A=136-245. DR PDB; 1MEK; NMR; -; A=18-137. DR PDB; 1X5C; NMR; -; A=368-475. DR PDB; 2BJX; NMR; -; A=136-245. DR PDB; 2K18; NMR; -; A=135-357. DR PDB; 3BJ5; X-ray; 2.20 A; A=230-368. DR PDB; 3UEM; X-ray; 2.29 A; A=137-479. DR PDB; 4EKZ; X-ray; 2.51 A; A=18-479. DR PDB; 4EL1; X-ray; 2.88 A; A/B=18-479. DR PDB; 4JU5; X-ray; 2.28 A; A/B=135-367. DR PDB; 6I7S; X-ray; 2.50 A; A/B=18-508. DR PDB; 7ZSC; X-ray; 3.85 A; C/D=18-508. DR PDB; 8EOJ; EM; 3.07 A; A=1-508. DR PDB; 8GDY; X-ray; 2.05 A; A/B=18-137. DR PDBsum; 1BJX; -. DR PDBsum; 1MEK; -. DR PDBsum; 1X5C; -. DR PDBsum; 2BJX; -. DR PDBsum; 2K18; -. DR PDBsum; 3BJ5; -. DR PDBsum; 3UEM; -. DR PDBsum; 4EKZ; -. DR PDBsum; 4EL1; -. DR PDBsum; 4JU5; -. DR PDBsum; 6I7S; -. DR PDBsum; 7ZSC; -. DR PDBsum; 8EOJ; -. DR PDBsum; 8GDY; -. DR AlphaFoldDB; P07237; -. DR BMRB; P07237; -. DR EMDB; EMD-28377; -. DR SMR; P07237; -. DR BioGRID; 111073; 444. DR CORUM; P07237; -. DR DIP; DIP-32979N; -. DR IntAct; P07237; 216. DR MINT; P07237; -. DR STRING; 9606.ENSP00000327801; -. DR BindingDB; P07237; -. DR ChEMBL; CHEMBL5422; -. DR DrugBank; DB11638; Artenimol. DR DrugBank; DB09130; Copper. DR DrugBank; DB03615; Ribostamycin. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR GlyGen; P07237; 8 sites, 2 O-linked glycans (8 sites). DR iPTMnet; P07237; -. DR MetOSite; P07237; -. DR PhosphoSitePlus; P07237; -. DR SwissPalm; P07237; -. DR BioMuta; P4HB; -. DR DMDM; 2507460; -. DR OGP; P07237; -. DR REPRODUCTION-2DPAGE; IPI00010796; -. DR REPRODUCTION-2DPAGE; P07237; -. DR jPOST; P07237; -. DR MassIVE; P07237; -. DR PaxDb; 9606-ENSP00000327801; -. DR PeptideAtlas; P07237; -. DR PRIDE; P07237; -. DR ProteomicsDB; 51976; -. DR Pumba; P07237; -. DR TopDownProteomics; P07237; -. DR Antibodypedia; 3250; 672 antibodies from 45 providers. DR DNASU; 5034; -. DR Ensembl; ENST00000331483.9; ENSP00000327801.4; ENSG00000185624.16. DR GeneID; 5034; -. DR KEGG; hsa:5034; -. DR MANE-Select; ENST00000331483.9; ENSP00000327801.4; NM_000918.4; NP_000909.2. DR UCSC; uc002kbn.2; human. DR AGR; HGNC:8548; -. DR CTD; 5034; -. DR DisGeNET; 5034; -. DR GeneCards; P4HB; -. DR HGNC; HGNC:8548; P4HB. DR HPA; ENSG00000185624; Tissue enhanced (liver, pancreas). DR MalaCards; P4HB; -. DR MIM; 112240; phenotype. DR MIM; 176790; gene. DR neXtProt; NX_P07237; -. DR OpenTargets; ENSG00000185624; -. DR Orphanet; 2050; Cole-Carpenter syndrome. DR Orphanet; 216796; Osteogenesis imperfecta type 1. DR PharmGKB; PA32876; -. DR VEuPathDB; HostDB:ENSG00000185624; -. DR eggNOG; KOG0190; Eukaryota. DR GeneTree; ENSGT00940000157351; -. DR InParanoid; P07237; -. DR OMA; FFGMKKD; -. DR OrthoDB; 72053at2759; -. DR PhylomeDB; P07237; -. DR TreeFam; TF106381; -. DR BioCyc; MetaCyc:HS06845-MONOMER; -. DR BRENDA; 5.3.4.1; 2681. DR PathwayCommons; P07237; -. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR Reactome; R-HSA-264876; Insulin processing. DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis. DR Reactome; R-HSA-8866423; VLDL assembly. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR Reactome; R-HSA-8963888; Chylomicron assembly. DR Reactome; R-HSA-8964041; LDL remodeling. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR SignaLink; P07237; -. DR SIGNOR; P07237; -. DR BioGRID-ORCS; 5034; 26 hits in 1172 CRISPR screens. DR ChiTaRS; P4HB; human. DR EvolutionaryTrace; P07237; -. DR GeneWiki; P4HB; -. DR GenomeRNAi; 5034; -. DR Pharos; P07237; Tchem. DR PRO; PR:P07237; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P07237; protein. DR Bgee; ENSG00000185624; Expressed in stromal cell of endometrium and 207 other cell types or tissues. DR ExpressionAtlas; P07237; baseline and differential. DR GO; GO:0005856; C:cytoskeleton; IDA:ARUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IEA:Ensembl. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IDA:ARUK-UCL. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016222; C:procollagen-proline 4-dioxygenase complex; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL. DR GO; GO:0003779; F:actin binding; IPI:ARUK-UCL. DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl. DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB. DR GO; GO:0004656; F:procollagen-proline 4-dioxygenase activity; TAS:ProtInc. DR GO; GO:0003756; F:protein disulfide isomerase activity; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0016972; F:thiol oxidase activity; IDA:FlyBase. DR GO; GO:0071456; P:cellular response to hypoxia; IMP:BHF-UCL. DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IEA:Ensembl. DR GO; GO:0030070; P:insulin processing; TAS:Reactome. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038155; P:interleukin-23-mediated signaling pathway; TAS:Reactome. DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:MGI. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:ARUK-UCL. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:ARUK-UCL. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IMP:UniProtKB. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IDA:FlyBase. DR GO; GO:1902175; P:regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:BHF-UCL. DR CDD; cd02961; PDI_a_family; 1. DR CDD; cd02995; PDI_a_PDI_a'_C; 1. DR CDD; cd02982; PDI_b'_family; 1. DR CDD; cd02981; PDI_b_family; 1. DR DisProt; DP02637; -. DR FunFam; 3.40.30.10:FF:000023; Protein disulfide-isomerase; 1. DR FunFam; 3.40.30.10:FF:000030; Protein disulfide-isomerase; 1. DR FunFam; 3.40.30.10:FF:000110; Protein disulfide-isomerase; 1. DR FunFam; 3.40.30.10:FF:000027; protein disulfide-isomerase A2; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 4. DR InterPro; IPR005788; PDI_thioredoxin-like_dom. DR InterPro; IPR005792; Prot_disulphide_isomerase. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR017937; Thioredoxin_CS. DR InterPro; IPR013766; Thioredoxin_domain. DR NCBIfam; TIGR01130; ER_PDI_fam; 1. DR NCBIfam; TIGR01126; pdi_dom; 2. DR PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1. DR PANTHER; PTHR18929:SF101; PROTEIN DISULFIDE-ISOMERASE; 1. DR Pfam; PF00085; Thioredoxin; 2. DR Pfam; PF13848; Thioredoxin_6; 1. DR PRINTS; PR00421; THIOREDOXIN. DR SUPFAM; SSF52833; Thioredoxin-like; 4. DR PROSITE; PS00014; ER_TARGET; 1. DR PROSITE; PS00194; THIOREDOXIN_1; 2. DR PROSITE; PS51352; THIOREDOXIN_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell membrane; Chaperone; Craniosynostosis; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Endoplasmic reticulum; Isomerase; Membrane; Osteogenesis imperfecta; KW Phosphoprotein; Proteomics identification; Redox-active center; KW Reference proteome; Repeat; Signal. FT SIGNAL 1..17 FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:2079031, ECO:0000269|PubMed:9150948, FT ECO:0000269|Ref.10, ECO:0007744|PubMed:25944712" FT CHAIN 18..508 FT /note="Protein disulfide-isomerase" FT /id="PRO_0000034195" FT DOMAIN 18..134 FT /note="Thioredoxin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT DOMAIN 349..475 FT /note="Thioredoxin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT REGION 471..508 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 505..508 FT /note="Prevents secretion from ER" FT COMPBIAS 478..500 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 53 FT /note="Nucleophile" FT ACT_SITE 56 FT /note="Nucleophile" FT ACT_SITE 397 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 400 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT SITE 54 FT /note="Contributes to redox potential value" FT SITE 55 FT /note="Contributes to redox potential value" FT SITE 120 FT /note="Lowers pKa of C-terminal Cys of first active site" FT SITE 398 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 399 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 461 FT /note="Lowers pKa of C-terminal Cys of second active site" FT /evidence="ECO:0000250" FT MOD_RES 200 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P09103" FT MOD_RES 222 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P09103" FT MOD_RES 271 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P09103" FT MOD_RES 331 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32149426" FT MOD_RES 357 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039, FT ECO:0000269|PubMed:32149426" FT MOD_RES 427 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:32149426" FT DISULFID 53..56 FT /note="Redox-active" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691, FT ECO:0000269|PubMed:8672469" FT DISULFID 397..400 FT /note="Redox-active" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT VARIANT 393 FT /note="Y -> C (in CLCRP1; impairs ability to act as a FT disulfide isomerase enzyme; dbSNP:rs786204843)" FT /evidence="ECO:0000269|PubMed:25683117" FT /id="VAR_073440" FT MUTAGEN 128 FT /note="W->I: Reduced interaction with ERN1. Abolishes FT interaction with ERN1; when associated with W-403." FT /evidence="ECO:0000269|PubMed:32149426" FT MUTAGEN 331 FT /note="S->E: Phosphomimetic mutant. Does not affect enzyme FT or chaperone activity." FT /evidence="ECO:0000269|PubMed:32149426" FT MUTAGEN 357 FT /note="S->A: Abolishes phosphorylation at this site but FT protein is still phosphorylated at other sites. No changes FT in chaperone or enzyme activity." FT /evidence="ECO:0000269|PubMed:32149426" FT MUTAGEN 357 FT /note="S->E: Phosphomimetic mutant. Reduced resistance to FT protease digestion, sugesting adoption of an open FT conformation. Increased chaperone activity. Decreased FT enzyme activity. Increased binding to ERN1." FT /evidence="ECO:0000269|PubMed:32149426" FT MUTAGEN 403 FT /note="L->W: Reduced interaction with ERN1. Abolishes FT interaction with ERN1; when associated with I-128." FT /evidence="ECO:0000269|PubMed:32149426" FT MUTAGEN 427 FT /note="S->E: Phosphomimetic mutant. Does not affect enzyme FT or chaperone activity. Does not increase binding to ERN1." FT /evidence="ECO:0000269|PubMed:32149426" FT CONFLICT 10..11 FT /note="AV -> PW (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT CONFLICT 21 FT /note="E -> D (in Ref. 13; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 24 FT /note="D -> V (in Ref. 13; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 44..45 FT /note="LL -> PP (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT CONFLICT 49 FT /note="Y -> H (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT CONFLICT 141 FT /note="P -> R (in Ref. 2; AAA61169)" FT /evidence="ECO:0000305" FT CONFLICT 360..362 FT /note="LPE -> RAG (in Ref. 2; AAA61169)" FT /evidence="ECO:0000305" FT CONFLICT 372 FT /note="L -> P (in Ref. 2; AAA61169)" FT /evidence="ECO:0000305" FT CONFLICT 439 FT /note="S -> G (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT CONFLICT 444 FT /note="K -> G (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT CONFLICT 460 FT /note="E -> Q (in Ref. 15; CAA30112)" FT /evidence="ECO:0000305" FT CONFLICT 481 FT /note="D -> V (in Ref. 1; CAA28775)" FT /evidence="ECO:0000305" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:4EKZ" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:8GDY" FT HELIX 31..40 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 42..49 FT /evidence="ECO:0007829|PDB:8GDY" FT HELIX 54..72 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 78..83 FT /evidence="ECO:0007829|PDB:8GDY" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:8GDY" FT HELIX 88..93 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 98..106 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:4EL1" FT HELIX 122..133 FT /evidence="ECO:0007829|PDB:8GDY" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:3UEM" FT HELIX 143..151 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 153..160 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:6I7S" FT HELIX 167..178 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 184..187 FT /evidence="ECO:0007829|PDB:4JU5" FT HELIX 190..195 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 199..209 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:4JU5" FT HELIX 222..232 FT /evidence="ECO:0007829|PDB:4JU5" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:3BJ5" FT TURN 242..244 FT /evidence="ECO:0007829|PDB:3BJ5" FT HELIX 245..249 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 250..252 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 255..260 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:3BJ5" FT HELIX 268..280 FT /evidence="ECO:0007829|PDB:3BJ5" FT TURN 281..285 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 287..291 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:8EOJ" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:3BJ5" FT HELIX 299..304 FT /evidence="ECO:0007829|PDB:3BJ5" FT HELIX 309..311 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 313..319 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 330..332 FT /evidence="ECO:0007829|PDB:4EKZ" FT HELIX 336..347 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 353..355 FT /evidence="ECO:0007829|PDB:3BJ5" FT HELIX 362..364 FT /evidence="ECO:0007829|PDB:3BJ5" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:3UEM" FT TURN 374..376 FT /evidence="ECO:0007829|PDB:3UEM" FT HELIX 377..381 FT /evidence="ECO:0007829|PDB:3UEM" FT STRAND 387..393 FT /evidence="ECO:0007829|PDB:3UEM" FT HELIX 398..413 FT /evidence="ECO:0007829|PDB:3UEM" FT TURN 414..416 FT /evidence="ECO:0007829|PDB:3UEM" FT STRAND 418..426 FT /evidence="ECO:0007829|PDB:3UEM" FT TURN 427..429 FT /evidence="ECO:0007829|PDB:3UEM" FT STRAND 439..446 FT /evidence="ECO:0007829|PDB:3UEM" FT STRAND 448..451 FT /evidence="ECO:0007829|PDB:3UEM" FT HELIX 463..470 FT /evidence="ECO:0007829|PDB:3UEM" FT TURN 471..473 FT /evidence="ECO:0007829|PDB:3UEM" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:8EOJ" SQ SEQUENCE 508 AA; 57116 MW; 906CE6D9900B8FCE CRC64; MLRRALLCLA VAALVRADAP EEEDHVLVLR KSNFAEALAA HKYLLVEFYA PWCGHCKALA PEYAKAAGKL KAEGSEIRLA KVDATEESDL AQQYGVRGYP TIKFFRNGDT ASPKEYTAGR EADDIVNWLK KRTGPAATTL PDGAAAESLV ESSEVAVIGF FKDVESDSAK QFLQAAEAID DIPFGITSNS DVFSKYQLDK DGVVLFKKFD EGRNNFEGEV TKENLLDFIK HNQLPLVIEF TEQTAPKIFG GEIKTHILLF LPKSVSDYDG KLSNFKTAAE SFKGKILFIF IDSDHTDNQR ILEFFGLKKE ECPAVRLITL EEEMTKYKPE SEELTAERIT EFCHRFLEGK IKPHLMSQEL PEDWDKQPVK VLVGKNFEDV AFDEKKNVFV EFYAPWCGHC KQLAPIWDKL GETYKDHENI VIAKMDSTAN EVEAVKVHSF PTLKFFPASA DRTVIDYNGE RTLDGFKKFL ESGGQDGAGD DDDLEDLEEA EEPDMEEDDD QKAVKDEL //