PDIA6_MOUSE
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 03-AUG-2022, entry version 162.
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, Pancreas,
RC 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; 31.
DR IntAct; Q922R8; 2.
DR MINT; Q922R8; -.
DR STRING; 10090.ENSMUSP00000052912; -.
DR iPTMnet; Q922R8; -.
DR PhosphoSitePlus; Q922R8; -.
DR SwissPalm; Q922R8; -.
DR REPRODUCTION-2DPAGE; Q922R8; -.
DR EPD; Q922R8; -.
DR jPOST; Q922R8; -.
DR MaxQB; Q922R8; -.
DR PaxDb; Q922R8; -.
DR PeptideAtlas; Q922R8; -.
DR PRIDE; Q922R8; -.
DR ProteomicsDB; 288081; -.
DR DNASU; 71853; -.
DR GeneID; 71853; -.
DR KEGG; mmu:71853; -.
DR CTD; 10130; -.
DR MGI; MGI:1919103; Pdia6.
DR eggNOG; KOG0191; Eukaryota.
DR InParanoid; Q922R8; -.
DR OrthoDB; 840943at2759; -.
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 74 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 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; 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
