ID   PDI_DROME               Reviewed;         496 AA.
AC   P54399; Q53YH5; Q86PE2; Q8IQL8; Q9VUL7;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 189.
DE   RecName: Full=Protein disulfide-isomerase;
DE            Short=PDI;
DE            Short=dPDI;
DE            EC=5.3.4.1;
DE   Flags: Precursor;
GN   Name=Pdi; ORFNames=CG6988;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RC   TISSUE=Head;
RX   PubMed=7787847; DOI=10.1016/0965-1748(95)00001-c;
RA   McKay R.R., Zhu L., Shortridge R.D.;
RT   "A Drosophila gene that encodes a member of the protein disulfide
RT   isomerase/phospholipase C-alpha family.";
RL   Insect Biochem. Mol. Biol. 25:647-654(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D).
RC   STRAIN=Berkeley; TISSUE=Embryo, and Head;
RA   Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA   Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA   Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA   Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA   Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL   Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Participates in the folding of proteins containing disulfide
CC       bonds. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC         EC=5.3.4.1;
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC       ProRule:PRU10138}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A;
CC         IsoId=P54399-1; Sequence=Displayed;
CC       Name=D;
CC         IsoId=P54399-2; Sequence=VSP_035858;
CC   -!- TISSUE SPECIFICITY: Expressed in all head and body tissues.
CC       {ECO:0000269|PubMed:7787847}.
CC   -!- DEVELOPMENTAL STAGE: Ubiquitously expressed during development.
CC       {ECO:0000269|PubMed:7787847}.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAO24936.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; U18973; AAA86480.1; -; mRNA.
DR   EMBL; AE014296; AAF49659.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN11793.1; -; Genomic_DNA.
DR   EMBL; BT001544; AAN71299.1; -; mRNA.
DR   EMBL; BT003181; AAO24936.1; ALT_FRAME; mRNA.
DR   EMBL; BT011488; AAR99146.1; -; mRNA.
DR   EMBL; BT012439; AAS93710.1; -; mRNA.
DR   RefSeq; NP_001287070.1; NM_001300141.1. [P54399-1]
DR   RefSeq; NP_524079.1; NM_079355.3. [P54399-1]
DR   AlphaFoldDB; P54399; -.
DR   SMR; P54399; -.
DR   BioGRID; 64973; 85.
DR   DIP; DIP-21766N; -.
DR   IntAct; P54399; 21.
DR   STRING; 7227.FBpp0312224; -.
DR   GlyGen; P54399; 1 site, 1 O-linked glycan (1 site).
DR   PaxDb; 7227-FBpp0075401; -.
DR   DNASU; 39651; -.
DR   EnsemblMetazoa; FBtr0075648; FBpp0075401; FBgn0286818. [P54399-1]
DR   EnsemblMetazoa; FBtr0346644; FBpp0312224; FBgn0286818. [P54399-1]
DR   GeneID; 39651; -.
DR   KEGG; dme:Dmel_CG6988; -.
DR   UCSC; CG6988-RD; d. melanogaster.
DR   AGR; FB:FBgn0286818; -.
DR   CTD; 39651; -.
DR   FlyBase; FBgn0286818; Pdi.
DR   VEuPathDB; VectorBase:FBgn0286818; -.
DR   eggNOG; KOG0190; Eukaryota.
DR   HOGENOM; CLU_025879_1_0_1; -.
DR   InParanoid; P54399; -.
DR   OMA; FFGMKKD; -.
DR   OrthoDB; 5399045at2759; -.
DR   PhylomeDB; P54399; -.
DR   Reactome; R-DME-1650814; Collagen biosynthesis and modifying enzymes.
DR   Reactome; R-DME-264876; Insulin processing.
DR   Reactome; R-DME-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-DME-5358346; Hedgehog ligand biogenesis.
DR   Reactome; R-DME-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-DME-8964041; LDL remodeling.
DR   BioGRID-ORCS; 39651; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; Pdi; fly.
DR   GenomeRNAi; 39651; -.
DR   PRO; PR:P54399; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0286818; Expressed in saliva-secreting gland and 26 other cell types or tissues.
DR   ExpressionAtlas; P54399; baseline and differential.
DR   GO; GO:0060187; C:cell pole; IDA:FlyBase.
DR   GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR   GO; GO:0012505; C:endomembrane system; HDA:FlyBase.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR   GO; GO:0045169; C:fusome; IDA:FlyBase.
DR   GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR   GO; GO:0005635; C:nuclear envelope; IDA:FlyBase.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; IDA:FlyBase.
DR   GO; GO:0070732; C:spindle envelope; IDA:FlyBase.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; IBA:GO_Central.
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; IPR005788; PDI_thioredoxin-like_dom.
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   NCBIfam; TIGR01126; pdi_dom; 2.
DR   PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1.
DR   PANTHER; PTHR18929:SF246; PROTEIN DISULFIDE-ISOMERASE; 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; 2.
DR   PROSITE; PS51352; THIOREDOXIN_2; 2.
DR   Genevisible; P54399; DM.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Disulfide bond; Endoplasmic reticulum; Isomerase;
KW   Redox-active center; Reference proteome; Repeat; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..496
FT                   /note="Protein disulfide-isomerase"
FT                   /id="PRO_0000034202"
FT   DOMAIN          19..134
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          349..474
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          473..496
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           493..496
FT                   /note="Prevents secretion from ER"
FT   COMPBIAS        476..496
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        56
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        59
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        397
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        400
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   SITE            57
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            58
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            120
FT                   /note="Lowers pKa of C-terminal Cys of first active site"
FT                   /evidence="ECO:0000250"
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            460
FT                   /note="Lowers pKa of C-terminal Cys of second active site"
FT                   /evidence="ECO:0000250"
FT   DISULFID        56..59
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        397..400
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   VAR_SEQ         1..306
FT                   /note="Missing (in isoform D)"
FT                   /evidence="ECO:0000303|Ref.5"
FT                   /id="VSP_035858"
FT   CONFLICT        406
FT                   /note="I -> T (in Ref. 5; AAO24936)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   496 AA;  55781 MW;  EB6E04C4216E7A81 CRC64;
     MKFLICALFL AASYVAASAE AEVKVEEGVL VATVDNFKQL IADNEFVLVE FYAPWCGHCK
     ALAPEYAKAA QQLAEKESPI KLAKVDATVE GELAEQYAVR GYPTLKFFRS GSPVEYSGGR
     QAADIIAWVT KKTGPPAKDL TSVADAEQFL KDNEIAIIGF FKDLESEEAK TFTKVANALD
     SFVFGVSSNA DVIAKYEAKD NGVVLFKPFD DKKSVFEGEL NEENLKKFAQ VQSLPLIVDF
     NHESASKIFG GSIKSHLLFF VSREGGHIEK YVDPLKEIAK KYRDDILFVT ISSDEEDHTR
     IFEFFGMNKE EVPTIRLIKL EEDMAKYKPE SDDLSAETIE AFLKKFLDGK LKQHLLSQEL
     PEDWDKNPVK VLVSSNFESV ALDKSKSVLV EFYAPWCGHC KQLAPIYDQL AEKYKDNEDI
     VIAKMDSTAN ELESIKISSF PTIKYFRKED NKVIDFNLDR TLDDFVKFLD ANGEVADSEP
     VEETEEEEEA PKKDEL
//