PDIA6_HUMAN
ID PDIA6_HUMAN Reviewed; 440 AA.
AC Q15084; B3KY95; B5MCQ5; B7Z254; B7Z4M8; F8WA83; Q53RC7; Q6ZSH5; Q99778;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Protein disulfide-isomerase A6;
DE EC=5.3.4.1 {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936};
DE AltName: Full=Endoplasmic reticulum protein 5;
DE Short=ER protein 5;
DE Short=ERp5;
DE AltName: Full=Protein disulfide isomerase P5;
DE AltName: Full=Thioredoxin domain-containing protein 7;
DE Flags: Precursor;
GN Name=PDIA6; Synonyms=ERP5, P5, TXNDC7;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=7590364; DOI=10.1016/0378-1119(95)00474-k;
RA Hayano T., Kikuchi M.;
RT "Cloning and sequencing of the cDNA encoding human P5.";
RL Gene 164:377-378(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), AND
RP VARIANT ARG-214.
RC TISSUE=Amygdala, and Thalamus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-440 (ISOFORM 1), AND VARIANT
RP ARG-214.
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [7]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 20-38.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [8]
RP PROTEIN SEQUENCE OF 20-34, FUNCTION, ENZYME ACTIVITY, INTERACTION WITH
RP ITGB3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15466936; DOI=10.1182/blood-2004-02-0608;
RA Jordan P.A., Stevens J.M., Hubbard G.P., Barrett N.E., Sage T., Authi K.S.,
RA Gibbins J.M.;
RT "A role for the thiol isomerase protein ERP5 in platelet function.";
RL Blood 105:1500-1507(2005).
RN [9]
RP PROTEIN SEQUENCE OF 103-138; 195-212; 217-231; 242-289; 314-328 AND
RP 374-386.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [10]
RP FUNCTION, ENZYME ACTIVITY, AND MUTAGENESIS OF CYS-55; CYS-58; CYS-190 AND
RP CYS-193.
RX PubMed=12204115; DOI=10.1093/oxfordjournals.jbchem.a003242;
RA Kikuchi M., Doi E., Tsujimoto I., Horibe T., Tsujimoto Y.;
RT "Functional analysis of human P5, a protein disulfide isomerase
RT homologue.";
RL J. Biochem. 132:451-455(2002).
RN [11]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.e02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein complexes in
RT endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [16]
RP INTERACTION WITH MICA.
RX PubMed=17495932; DOI=10.1038/nature05768;
RA Kaiser B.K., Yim D., Chow I.-T., Gonzalez S., Dai Z., Mann H.H.,
RA Strong R.K., Groh V., Spies T.;
RT "Disulphide-isomerase-enabled shedding of tumour-associated NKG2D
RT ligands.";
RL Nature 447:482-486(2007).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-428, AND
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 [26]
RP FUNCTION, INTERACTION WITH ERN1 AND EIF2AK3, AND MUTAGENESIS OF CYS-58 AND
RP CYS-193.
RX PubMed=24508390; DOI=10.1016/j.molcel.2014.01.004;
RA Eletto D., Eletto D., Dersh D., Gidalevitz T., Argon Y.;
RT "Protein disulfide isomerase A6 controls the decay of IRE1alpha signaling
RT via disulfide-dependent association.";
RL Mol. Cell 53:562-576(2014).
RN [27]
RP PHOSPHORYLATION AT SER-156.
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 [28]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-19, 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 [29]
RP STRUCTURE BY NMR OF 161-280.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the second thioredoxin-like domain of human
RT protein disulfide-isomerase A6.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: May function as a chaperone that inhibits aggregation of
CC misfolded proteins (PubMed:12204115). Negatively regulates the unfolded
CC protein response (UPR) through binding to UPR sensors such as ERN1,
CC which in turn inactivates ERN1 signaling (PubMed:24508390). May also
CC regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a
CC role in platelet aggregation and activation by agonists such as
CC convulxin, collagen and thrombin (PubMed:15466936).
CC {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936,
CC ECO:0000269|PubMed:24508390}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000269|PubMed:12204115,
CC ECO:0000269|PubMed:15466936};
CC -!- SUBUNIT: Part of a large chaperone multiprotein complex comprising
CC DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1
CC and very small amounts of ERP29, but not, or at very low levels, CALR
CC nor CANX (PubMed:12475965). Interacts with MICA on the surface of tumor
CC cells, leading to MICA disulfide bond reduction which is required for
CC its release from tumor cells (PubMed:17495932). Interacts with ITGB3
CC following platelet stimulation (PubMed:15466936). Interacts with ERN1;
CC the interaction is direct (PubMed:24508390). Interacts with EIF2AK3
CC (PubMed:24508390). {ECO:0000269|PubMed:12475965,
CC ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:17495932,
CC ECO:0000269|PubMed:24508390}.
CC -!- INTERACTION:
CC Q15084; P05067: APP; NbExp=3; IntAct=EBI-1043087, EBI-77613;
CC Q15084; O43681: GET3; NbExp=3; IntAct=EBI-1043087, EBI-2515857;
CC Q15084; P11021: HSPA5; NbExp=2; IntAct=EBI-1043087, EBI-354921;
CC Q15084; Q13162: PRDX4; NbExp=2; IntAct=EBI-1043087, EBI-2211957;
CC Q15084; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-1043087, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:15466936}. Cell membrane
CC {ECO:0000269|PubMed:15466936}. Melanosome {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV (PubMed:12643545).
CC {ECO:0000269|PubMed:12643545}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q15084-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15084-2; Sequence=VSP_021803;
CC Name=3;
CC IsoId=Q15084-3; Sequence=VSP_054370;
CC Name=4;
CC IsoId=Q15084-4; Sequence=VSP_055173;
CC Name=5;
CC IsoId=Q15084-5; Sequence=VSP_055174;
CC -!- TISSUE SPECIFICITY: Expressed in platelets (at protein level).
CC {ECO:0000269|PubMed:15466936}.
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
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DR EMBL; D49489; BAA08450.1; -; mRNA.
DR EMBL; AK127433; BAC86977.1; -; mRNA.
DR EMBL; AK131234; BAG54757.1; -; mRNA.
DR EMBL; AK289428; BAF82117.1; -; mRNA.
DR EMBL; AK294347; BAH11740.1; -; mRNA.
DR EMBL; AK297547; BAH12614.1; -; mRNA.
DR EMBL; AC092687; AAY24070.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00950.1; -; Genomic_DNA.
DR EMBL; BC001312; AAH01312.1; -; mRNA.
DR EMBL; U79278; AAB50217.1; -; mRNA.
DR CCDS; CCDS1675.1; -. [Q15084-1]
DR CCDS; CCDS62852.1; -. [Q15084-3]
DR CCDS; CCDS62853.1; -. [Q15084-4]
DR CCDS; CCDS62854.1; -. [Q15084-2]
DR CCDS; CCDS62855.1; -. [Q15084-5]
DR PIR; JC4369; JC4369.
DR RefSeq; NP_001269633.1; NM_001282704.1. [Q15084-2]
DR RefSeq; NP_001269634.1; NM_001282705.1. [Q15084-5]
DR RefSeq; NP_001269635.1; NM_001282706.1. [Q15084-4]
DR RefSeq; NP_001269636.1; NM_001282707.1. [Q15084-3]
DR RefSeq; NP_005733.1; NM_005742.3. [Q15084-1]
DR PDB; 1X5D; NMR; -; A=161-280.
DR PDB; 3VWW; X-ray; 1.93 A; A/B=25-140.
DR PDB; 3W8J; X-ray; 2.10 A; A/B=20-140.
DR PDB; 4EF0; X-ray; 1.50 A; A/B=27-140.
DR PDB; 4GWR; X-ray; 1.81 A; A/B=160-274.
DR PDBsum; 1X5D; -.
DR PDBsum; 3VWW; -.
DR PDBsum; 3W8J; -.
DR PDBsum; 4EF0; -.
DR PDBsum; 4GWR; -.
DR AlphaFoldDB; Q15084; -.
DR SMR; Q15084; -.
DR BioGRID; 115434; 247.
DR CORUM; Q15084; -.
DR IntAct; Q15084; 120.
DR MINT; Q15084; -.
DR STRING; 9606.ENSP00000385385; -.
DR BindingDB; Q15084; -.
DR ChEMBL; CHEMBL2146308; -.
DR GlyGen; Q15084; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15084; -.
DR PhosphoSitePlus; Q15084; -.
DR SwissPalm; Q15084; -.
DR BioMuta; PDIA6; -.
DR DMDM; 2501205; -.
DR OGP; Q15084; -.
DR REPRODUCTION-2DPAGE; IPI00644989; -.
DR REPRODUCTION-2DPAGE; Q15084; -.
DR CPTAC; CPTAC-250; -.
DR EPD; Q15084; -.
DR jPOST; Q15084; -.
DR MassIVE; Q15084; -.
DR MaxQB; Q15084; -.
DR PaxDb; Q15084; -.
DR PeptideAtlas; Q15084; -.
DR PRIDE; Q15084; -.
DR ProteomicsDB; 30450; -.
DR ProteomicsDB; 60433; -. [Q15084-1]
DR ProteomicsDB; 60434; -. [Q15084-2]
DR ProteomicsDB; 6087; -.
DR ProteomicsDB; 6408; -.
DR Antibodypedia; 12607; 272 antibodies from 36 providers.
DR DNASU; 10130; -.
DR Ensembl; ENST00000272227.8; ENSP00000272227.4; ENSG00000143870.13. [Q15084-1]
DR Ensembl; ENST00000381611.8; ENSP00000371024.4; ENSG00000143870.13. [Q15084-4]
DR Ensembl; ENST00000404371.6; ENSP00000385385.2; ENSG00000143870.13. [Q15084-2]
DR Ensembl; ENST00000404824.2; ENSP00000384459.2; ENSG00000143870.13. [Q15084-5]
DR Ensembl; ENST00000540494.5; ENSP00000438778.1; ENSG00000143870.13. [Q15084-3]
DR Ensembl; ENST00000617249.4; ENSP00000481892.1; ENSG00000143870.13. [Q15084-2]
DR GeneID; 10130; -.
DR KEGG; hsa:10130; -.
DR MANE-Select; ENST00000272227.8; ENSP00000272227.4; NM_005742.4; NP_005733.1.
DR UCSC; uc002rau.5; human. [Q15084-1]
DR CTD; 10130; -.
DR DisGeNET; 10130; -.
DR GeneCards; PDIA6; -.
DR HGNC; HGNC:30168; PDIA6.
DR HPA; ENSG00000143870; Low tissue specificity.
DR MIM; 611099; gene.
DR neXtProt; NX_Q15084; -.
DR OpenTargets; ENSG00000143870; -.
DR PharmGKB; PA134977905; -.
DR VEuPathDB; HostDB:ENSG00000143870; -.
DR eggNOG; KOG0191; Eukaryota.
DR GeneTree; ENSGT00940000155646; -.
DR HOGENOM; CLU_030311_0_0_1; -.
DR InParanoid; Q15084; -.
DR OMA; DDIWLVE; -.
DR OrthoDB; 840943at2759; -.
DR PhylomeDB; Q15084; -.
DR TreeFam; TF315231; -.
DR PathwayCommons; Q15084; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
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-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q15084; -.
DR SIGNOR; Q15084; -.
DR BioGRID-ORCS; 10130; 8 hits in 1074 CRISPR screens.
DR ChiTaRS; PDIA6; human.
DR EvolutionaryTrace; Q15084; -.
DR GenomeRNAi; 10130; -.
DR Pharos; Q15084; Tchem.
DR PRO; PR:Q15084; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q15084; protein.
DR Bgee; ENSG00000143870; Expressed in corpus epididymis and 213 other tissues.
DR ExpressionAtlas; Q15084; baseline and differential.
DR Genevisible; Q15084; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003756; F:protein disulfide isomerase activity; TAS:ProtInc.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR044569; PDIA6-like.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR PANTHER; PTHR45815; PTHR45815; 3.
DR Pfam; PF00085; Thioredoxin; 2.
DR SUPFAM; SSF52833; SSF52833; 3.
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; Alternative splicing; Cell membrane; Chaperone;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Isomerase; Membrane; Phosphoprotein; Redox-active center;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:15466936,
FT ECO:0000269|PubMed:19892738, ECO:0007744|PubMed:25944712"
FT CHAIN 20..440
FT /note="Protein disulfide-isomerase A6"
FT /id="PRO_0000034236"
FT DOMAIN 20..133
FT /note="Thioredoxin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 154..287
FT /note="Thioredoxin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 141..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 437..440
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT ACT_SITE 55
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 58
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 190
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 193
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 56
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 57
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 118
FT /note="Lowers pKa of C-terminal Cys of first active site"
FT /evidence="ECO:0000250"
FT SITE 191
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 192
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 256
FT /note="Lowers pKa of C-terminal Cys of second active site"
FT /evidence="ECO:0000250"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 156
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18318008,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT DISULFID 55..58
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DISULFID 190..193
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT VAR_SEQ 1..6
FT /note="MALLVL -> MRRDLREKLVWVCRPLAPVEVPANISSDFQPCSPTSPAHSLS
FT RKSPIMYPSTTMANAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021803"
FT VAR_SEQ 1..6
FT /note="MALLVL -> MYPSTTMANAP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055173"
FT VAR_SEQ 1..6
FT /note="MALLVL -> MRIITAPASKVSRGSNELMILARRSDRGSPTSPAHSLSRKSP
FT IMYPSTTMANAP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055174"
FT VAR_SEQ 1..5
FT /note="MALLV -> MI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054370"
FT VARIANT 214
FT /note="K -> R (in dbSNP:rs4807)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:9110174"
FT /id="VAR_022152"
FT MUTAGEN 55
FT /note="C->S: 50% decrease in enzyme activity; when
FT associated with S-58. Abolishes enzyme activity; when
FT associated with S-58; S-190 and S-193."
FT /evidence="ECO:0000269|PubMed:12204115"
FT MUTAGEN 58
FT /note="C->A: Accelerates dephosphorylation of ERN1; when
FT associated with A-193."
FT /evidence="ECO:0000269|PubMed:24508390"
FT MUTAGEN 58
FT /note="C->S: 50% decrease in enzyme activity; when
FT associated with S-55. 90% decrease in enzyme activity; when
FT associated with S-193. Abolishes enzyme activity; when
FT associated with S-55; S-190 and S-193."
FT /evidence="ECO:0000269|PubMed:12204115"
FT MUTAGEN 190
FT /note="C->S: 25% decrease in enzyme activity; when
FT associated with S-193. Abolishes enzyme activity; when
FT associated with S-55; S-58 and S-193."
FT /evidence="ECO:0000269|PubMed:12204115"
FT MUTAGEN 193
FT /note="C->A: Accelerates dephosphorylation of ERN1; when
FT associated with A-58."
FT /evidence="ECO:0000269|PubMed:24508390"
FT MUTAGEN 193
FT /note="C->S: 90% decrease in enzyme activity; when
FT associated with S-58. 25% decrease in enzyme activity; when
FT associated with S-190. Abolishes enzyme activity; when
FT associated with S-55; S-58 and S-190."
FT /evidence="ECO:0000269|PubMed:12204115"
FT CONFLICT 64
FT /note="E -> K (in Ref. 2; BAH12614)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="A -> V (in Ref. 2; BAH12614)"
FT /evidence="ECO:0000305"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4EF0"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:4EF0"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:4EF0"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:4EF0"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:4EF0"
FT HELIX 56..71
FT /evidence="ECO:0007829|PDB:4EF0"
FT TURN 72..75
FT /evidence="ECO:0007829|PDB:4EF0"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:4EF0"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:4EF0"
FT HELIX 87..92
FT /evidence="ECO:0007829|PDB:4EF0"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:4EF0"
FT HELIX 120..139
FT /evidence="ECO:0007829|PDB:4EF0"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:4GWR"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:4GWR"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:4GWR"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:4GWR"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:4GWR"
FT HELIX 191..211
FT /evidence="ECO:0007829|PDB:4GWR"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:4GWR"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:4GWR"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:4GWR"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:4GWR"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:1X5D"
FT HELIX 258..271
FT /evidence="ECO:0007829|PDB:4GWR"
SQ SEQUENCE 440 AA; 48121 MW; 06895409F0265D7C CRC64;
MALLVLGLVS CTFFLAVNGL YSSSDDVIEL TPSNFNREVI QSDSLWLVEF YAPWCGHCQR
LTPEWKKAAT ALKDVVKVGA VDADKHHSLG GQYGVQGFPT IKIFGSNKNR PEDYQGGRTG
EAIVDAALSA LRQLVKDRLG GRSGGYSSGK QGRSDSSSKK DVIELTDDSF DKNVLDSEDV
WMVEFYAPWC GHCKNLEPEW AAAASEVKEQ TKGKVKLAAV DATVNQVLAS RYGIRGFPTI
KIFQKGESPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDIAKRT CEEHQLCVVA
VLPHILDTGA AGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQSELETALG IGGFGYPAMA
AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG GAFPTIVERE PWDGRDGELP
VEDDIDLSDV ELDDLGKDEL
