ID   PDIA6_MOUSE             Reviewed;         440 AA.
AC   Q922R8; Q8BK54;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2005, sequence version 3.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=Protein disulfide-isomerase A6;
DE            EC=5.3.4.1 {ECO:0000250|UniProtKB:Q15084};
DE   AltName: Full=Thioredoxin domain-containing protein 7;
DE   Flags: Precursor;
GN   Name=Pdia6; Synonyms=Txndc7;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II; TISSUE=Mammary tumor;
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   [3]
RP   PROTEIN SEQUENCE OF 119-132 AND 393-409, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-428, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   FUNCTION.
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   [6]
RP   STRUCTURE BY NMR OF 16-132.
RG   RIKEN structural genomics initiative (RSGI);
RT   "The solution structure of the first thioredoxin domain of mouse protein
RT   disulfide-isomerase A6.";
RL   Submitted (OCT-2006) to the PDB data bank.
CC   -!- FUNCTION: May function as a chaperone that inhibits aggregation of
CC       misfolded proteins (PubMed:24508390). Negatively regulates the unfolded
CC       protein response (UPR) through binding to UPR sensors such as ERN1,
CC       which in turn inactivates ERN1 signaling (By similarity). May also
CC       regulate the UPR via the EIF2AK3 UPR sensor (By similarity). Plays a
CC       role in platelet aggregation and activation by agonists such as
CC       convulxin, collagen and thrombin (By similarity).
CC       {ECO:0000250|UniProtKB:Q15084, 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:0000250|UniProtKB:Q15084};
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. Interacts with MICA on the surface of tumor cells, leading to
CC       MICA disulfide bond reduction which is required for its release from
CC       tumor cells. Interacts with ITGB3 following platelet stimulation.
CC       Interacts with ERN1; the interaction is direct. Interacts with EIF2AK3.
CC       {ECO:0000250|UniProtKB:Q15084}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:Q15084}. Cell membrane
CC       {ECO:0000250|UniProtKB:Q15084}. Melanosome
CC       {ECO:0000250|UniProtKB:Q15084}.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH06865.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAC36392.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AK076558; BAC36392.1; ALT_INIT; mRNA.
DR   EMBL; BC006865; AAH06865.2; ALT_INIT; mRNA.
DR   CCDS; CCDS25826.1; -.
DR   RefSeq; NP_082235.1; NM_027959.3.
DR   PDB; 2DML; NMR; -; A=16-132.
DR   PDBsum; 2DML; -.
DR   AlphaFoldDB; Q922R8; -.
DR   SMR; Q922R8; -.
DR   BioGRID; 214980; 35.
DR   IntAct; Q922R8; 2.
DR   MINT; Q922R8; -.
DR   STRING; 10090.ENSMUSP00000052912; -.
DR   GlyGen; Q922R8; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q922R8; -.
DR   PhosphoSitePlus; Q922R8; -.
DR   SwissPalm; Q922R8; -.
DR   REPRODUCTION-2DPAGE; Q922R8; -.
DR   EPD; Q922R8; -.
DR   jPOST; Q922R8; -.
DR   MaxQB; Q922R8; -.
DR   PaxDb; 10090-ENSMUSP00000052912; -.
DR   PeptideAtlas; Q922R8; -.
DR   ProteomicsDB; 288081; -.
DR   Pumba; Q922R8; -.
DR   DNASU; 71853; -.
DR   GeneID; 71853; -.
DR   KEGG; mmu:71853; -.
DR   AGR; MGI:1919103; -.
DR   CTD; 10130; -.
DR   MGI; MGI:1919103; Pdia6.
DR   eggNOG; KOG0191; Eukaryota.
DR   InParanoid; Q922R8; -.
DR   OrthoDB; 52245at2759; -.
DR   Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR   BioGRID-ORCS; 71853; 1 hit in 79 CRISPR screens.
DR   ChiTaRS; Pdia6; mouse.
DR   EvolutionaryTrace; Q922R8; -.
DR   PRO; PR:Q922R8; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q922R8; Protein.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; ISS:UniProtKB.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; ISO:MGI.
DR   GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR   GO; GO:0070527; P:platelet aggregation; ISS:UniProtKB.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR   CDD; cd02983; P5_C; 1.
DR   CDD; cd03001; PDI_a_P5; 2.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 2.
DR   InterPro; IPR005788; PDI_thioredoxin-like_dom.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR017937; Thioredoxin_CS.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   NCBIfam; TIGR01126; pdi_dom; 2.
DR   PANTHER; PTHR45815; PROTEIN DISULFIDE-ISOMERASE A6; 1.
DR   PANTHER; PTHR45815:SF3; PROTEIN DISULFIDE-ISOMERASE A6; 1.
DR   Pfam; PF00085; Thioredoxin; 2.
DR   PRINTS; PR00421; THIOREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 3.
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; Cell membrane; Chaperone; Direct protein sequencing;
KW   Disulfide bond; Endoplasmic reticulum; Isomerase; Membrane; Phosphoprotein;
KW   Redox-active center; Reference proteome; Repeat; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..440
FT                   /note="Protein disulfide-isomerase A6"
FT                   /id="PRO_0000034238"
FT   DOMAIN          20..133
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          151..287
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          139..161
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          399..440
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   COMPBIAS        419..440
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         129
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         156
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15084"
FT   MOD_RES         158
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15084"
FT   MOD_RES         428
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
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   CONFLICT        224
FT                   /note="V -> M (in Ref. 1; BAC36392)"
FT                   /evidence="ECO:0000305"
FT   STRAND          25..29
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   TURN            32..34
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   HELIX           35..38
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   TURN            39..41
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   STRAND          46..51
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   HELIX           59..61
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   HELIX           62..71
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   TURN            72..75
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   STRAND          76..82
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   TURN            83..85
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   HELIX           87..93
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   STRAND          97..106
FT                   /evidence="ECO:0007829|PDB:2DML"
FT   HELIX           120..132
FT                   /evidence="ECO:0007829|PDB:2DML"
SQ   SEQUENCE   440 AA;  48100 MW;  E9FFA1F91AE06A20 CRC64;
     MARLVLGLVS CTFFLAVSGL YSSSDDVIEL TPSNFNREVI QSDGLWLVEF YAPWCGHCQR
     LTPEWKKAAT ALKDVVKVGA VNADKHQSLG GQYGVQGFPT IKIFGANKNK PEDYQGGRTG
     EAIVDAALSA LRQLVKDRLG GRSGGYSSGK QGRGDSSSKK DVVELTDDTF DKNVLDSEDV
     WMVEFYAPWC GHCKNLEPEW AAAATEVKEQ TKGKVKLAAV DATVNQVLAS RYGIKGFPTI
     KIFQKGESPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDIAKKT CEEHQLCVVA
     VLPHILDTGA AGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQYELENALG IGGFGYPAMA
     AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG GSFPTITPRE PWDGKDGELP
     VEDDIDLSDV ELDDLEKDEL
//