PDIA1_HUMAN
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 03-AUG-2022, entry version 261.
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:23475612, PubMed:26224785,
CC PubMed:16478722). 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; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-395883, EBI-10271580;
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; Q8NEG0: FAM71C; NbExp=3; IntAct=EBI-395883, EBI-752049;
CC P07237; Q53R41: FASTKD1; NbExp=3; IntAct=EBI-395883, EBI-3957005;
CC P07237; Q9ULW2: FZD10; NbExp=3; IntAct=EBI-395883, EBI-8803802;
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; 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; 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; 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}.
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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 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 AlphaFoldDB; P07237; -.
DR BMRB; P07237; -.
DR SMR; P07237; -.
DR BioGRID; 111073; 343.
DR CORUM; P07237; -.
DR DIP; DIP-32979N; -.
DR IntAct; P07237; 186.
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; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P07237; -.
DR MetOSite; P07237; -.
DR PhosphoSitePlus; P07237; -.
DR SwissPalm; P07237; -.
DR BioMuta; P4HB; -.
DR DMDM; 2507460; -.
DR DOSAC-COBS-2DPAGE; P07237; -.
DR OGP; P07237; -.
DR REPRODUCTION-2DPAGE; IPI00010796; -.
DR REPRODUCTION-2DPAGE; P07237; -.
DR SWISS-2DPAGE; P07237; -.
DR EPD; P07237; -.
DR jPOST; P07237; -.
DR MassIVE; P07237; -.
DR MaxQB; P07237; -.
DR PaxDb; P07237; -.
DR PeptideAtlas; P07237; -.
DR PRIDE; P07237; -.
DR ProteomicsDB; 51976; -.
DR TopDownProteomics; P07237; -.
DR Antibodypedia; 3250; 569 antibodies from 43 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 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; FCDRFLE; -.
DR OrthoDB; 462118at2759; -.
DR PhylomeDB; P07237; -.
DR TreeFam; TF106381; -.
DR BioCyc; MetaCyc:HS06845-MON; -.
DR BRENDA; 5.3.4.1; 2681.
DR PathwayCommons; P07237; -.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
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 BioGRID-ORCS; 5034; 26 hits in 1093 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 205 other tissues.
DR ExpressionAtlas; P07237; baseline and differential.
DR Genevisible; P07237; HS.
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:FlyBase.
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: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 DisProt; DP02637; -.
DR InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR005792; Prot_disulphide_isomerase.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 2.
DR SUPFAM; SSF52833; SSF52833; 4.
DR TIGRFAMs; TIGR01130; ER_PDI_fam; 1.
DR TIGRFAMs; TIGR01126; pdi_dom; 2.
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; Redox-active center; 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 476..508
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 increases 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:4EKZ"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:4EL1"
FT HELIX 34..40
FT /evidence="ECO:0007829|PDB:6I7S"
FT STRAND 42..49
FT /evidence="ECO:0007829|PDB:6I7S"
FT HELIX 54..71
FT /evidence="ECO:0007829|PDB:6I7S"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:6I7S"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:6I7S"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:6I7S"
FT STRAND 98..105
FT /evidence="ECO:0007829|PDB:6I7S"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:4EL1"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:4EL1"
FT HELIX 122..133
FT /evidence="ECO:0007829|PDB:6I7S"
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 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"
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
