ID   PDIA2_MOUSE             Reviewed;         527 AA.
AC   D3Z6P0; Q14AV9;
DT   15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   27-MAR-2024, entry version 93.
DE   RecName: Full=Protein disulfide-isomerase A2 {ECO:0000250|UniProtKB:Q13087};
DE            EC=5.3.4.1;
DE   AltName: Full=PDIp {ECO:0000250|UniProtKB:Q13087};
DE   Flags: Precursor;
GN   Name=Pdia2 {ECO:0000312|MGI:MGI:1916441};
GN   Synonyms=Pdip {ECO:0000250|UniProtKB:Q13087};
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 GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAI16672.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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] {ECO:0000305}
RP   TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX   PubMed=9115635; DOI=10.1089/dna.1997.16.269;
RA   Desilva M.G., Notkins A.L., Lan M.S.;
RT   "Molecular characterization of a pancreas-specific protein disulfide
RT   isomerase, PDIp.";
RL   DNA Cell Biol. 16:269-274(1997).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, Lung, Pancreas, and Spleen;
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).
CC   -!- FUNCTION: Acts as an intracellular estrogen-binding protein. May be
CC       involved in modulating cellular levels and biological functions of
CC       estrogens in the pancreas. May act as a chaperone that inhibits
CC       aggregation of misfolded proteins (By similarity).
CC       {ECO:0000250|UniProtKB:Q13087}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC         EC=5.3.4.1; Evidence={ECO:0000305};
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. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:Q13087, ECO:0000255|PROSITE-ProRule:PRU10138}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1 {ECO:0000269|PubMed:19468303};
CC         IsoId=D3Z6P0-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|PubMed:15489334};
CC         IsoId=D3Z6P0-2; Sequence=VSP_039293;
CC   -!- TISSUE SPECIFICITY: Highly expressed in pancreas.
CC       {ECO:0000269|PubMed:9115635}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:9115635}.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000255}.
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DR   EMBL; AC126438; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC116671; AAI16672.1; -; mRNA.
DR   CCDS; CCDS37510.1; -. [D3Z6P0-1]
DR   RefSeq; NP_001074539.1; NM_001081070.1. [D3Z6P0-1]
DR   AlphaFoldDB; D3Z6P0; -.
DR   SMR; D3Z6P0; -.
DR   BioGRID; 213283; 1.
DR   STRING; 10090.ENSMUSP00000035584; -.
DR   GlyCosmos; D3Z6P0; 3 sites, No reported glycans.
DR   GlyGen; D3Z6P0; 3 sites.
DR   iPTMnet; D3Z6P0; -.
DR   PhosphoSitePlus; D3Z6P0; -.
DR   MaxQB; D3Z6P0; -.
DR   PaxDb; 10090-ENSMUSP00000035584; -.
DR   PeptideAtlas; D3Z6P0; -.
DR   ProteomicsDB; 288078; -. [D3Z6P0-1]
DR   ProteomicsDB; 288079; -. [D3Z6P0-2]
DR   Antibodypedia; 22619; 413 antibodies from 30 providers.
DR   Ensembl; ENSMUST00000039113.14; ENSMUSP00000035584.8; ENSMUSG00000024184.16. [D3Z6P0-1]
DR   Ensembl; ENSMUST00000120333.8; ENSMUSP00000114080.2; ENSMUSG00000024184.16. [D3Z6P0-2]
DR   GeneID; 69191; -.
DR   KEGG; mmu:69191; -.
DR   UCSC; uc008bdo.1; mouse. [D3Z6P0-1]
DR   UCSC; uc012ans.1; mouse. [D3Z6P0-2]
DR   AGR; MGI:1916441; -.
DR   CTD; 64714; -.
DR   MGI; MGI:1916441; Pdia2.
DR   VEuPathDB; HostDB:ENSMUSG00000024184; -.
DR   eggNOG; KOG0190; Eukaryota.
DR   GeneTree; ENSGT00940000161859; -.
DR   HOGENOM; CLU_025879_1_0_1; -.
DR   InParanoid; D3Z6P0; -.
DR   OMA; FCHSVFS; -.
DR   OrthoDB; 5399045at2759; -.
DR   PhylomeDB; D3Z6P0; -.
DR   TreeFam; TF106381; -.
DR   BioGRID-ORCS; 69191; 1 hit in 81 CRISPR screens.
DR   ChiTaRS; Pdia2; mouse.
DR   PRO; PR:D3Z6P0; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; D3Z6P0; Protein.
DR   Bgee; ENSMUSG00000024184; Expressed in epithelium of stomach and 67 other cell types or tissues.
DR   ExpressionAtlas; D3Z6P0; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; TAS:MGI.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; ISO:MGI.
DR   GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR   GO; GO:0070527; P:platelet aggregation; IMP:MGI.
DR   GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR   CDD; cd02961; PDI_a_family; 1.
DR   CDD; cd02995; PDI_a_PDI_a'_C; 1.
DR   CDD; cd02982; PDI_b'_family; 1.
DR   CDD; cd02981; PDI_b_family; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 4.
DR   InterPro; IPR005792; Prot_disulphide_isomerase.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR017937; Thioredoxin_CS.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   NCBIfam; TIGR01130; ER_PDI_fam; 1.
DR   PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1.
DR   PANTHER; PTHR18929:SF93; PROTEIN DISULFIDE-ISOMERASE A2; 1.
DR   Pfam; PF00085; Thioredoxin; 2.
DR   Pfam; PF13848; Thioredoxin_6; 1.
DR   PRINTS; PR00421; THIOREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 4.
DR   PROSITE; PS00014; ER_TARGET; 1.
DR   PROSITE; PS00194; THIOREDOXIN_1; 1.
DR   PROSITE; PS51352; THIOREDOXIN_2; 2.
DR   Genevisible; D3Z6P0; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chaperone; Disulfide bond; Endoplasmic reticulum;
KW   Glycoprotein; Isomerase; Lipid-binding; Redox-active center;
KW   Reference proteome; Repeat; Signal; Steroid-binding.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..527
FT                   /note="Protein disulfide-isomerase A2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000394671"
FT   DOMAIN          29..155
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          355..499
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          20..41
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          495..527
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           524..527
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   ACT_SITE        74
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P07237"
FT   ACT_SITE        77
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P07237"
FT   ACT_SITE        421
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   ACT_SITE        424
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   SITE            75
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   SITE            76
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   SITE            422
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   SITE            423
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   SITE            485
FT                   /note="Lowers pKa of C-terminal Cys of second active site"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087"
FT   CARBOHYD        130
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        518
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        74..77
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087,
FT                   ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        421..424
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250|UniProtKB:Q13087,
FT                   ECO:0000255|PROSITE-ProRule:PRU00691"
FT   VAR_SEQ         184..186
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_039293"
SQ   SEQUENCE   527 AA;  58316 MW;  CF703D296B634441 CRC64;
     MDKQLLPVLL LLLGVSGSWG QGEEPGGPSE VLPEEPTGEE VPKEDGILVL NHRTLSLALQ
     EHSALMVEFY APWCGHCKEL APEYSKAAAL LAAESAVVTL AKVDGPAEPE LTKEFEVVGY
     PTLKFFQNGN RTNPEEYAGP KTAEGIAEWL RRRVGPSATH LEDEEGVQAL MAKWDMVVIG
     FFQDLQGKDM ATFLALAKDA LDMTFGFTDQ PQLFEKFGLT KDTVVLFKKF DEGRADFPVD
     KETGLDLGDL SRFLVIHSMH LVTEFNSQTS PKIFAAKILN HLLLFVNQTL AQHRELLTDF
     REAAPPFRGQ VLFVMVDVAA DNSHVLNYFG LKAEEAPTLR LINVETTKKY APTGVIAITA
     ASVAAFCQAV LHGEIKHYLL SQEIPPDWDQ GPVKTLVSKN FEQVAFDETK NVFVKFYAPW
     CSHCKEMAPA WEALAEKYKD REDIVIAELD ATANELEAFS VLGYPTLKFF PAGPDRKVID
     YKSTRDLETF SKFLDSGGHL PKEEPKEPAA SAPEAQANST LGPKEEL
//