ID   PDIA4_MOUSE             Reviewed;         638 AA.
AC   P08003; P15841; Q3TT79; Q3UJW0; Q6NXW4; Q8BMT8;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   30-NOV-2010, sequence version 3.
DT   24-JAN-2024, entry version 201.
DE   RecName: Full=Protein disulfide-isomerase A4;
DE            EC=5.3.4.1 {ECO:0000305|PubMed:23956175};
DE   AltName: Full=Endoplasmic reticulum resident protein 72;
DE            Short=ER protein 72;
DE            Short=ERp-72;
DE            Short=ERp72;
DE   Flags: Precursor;
GN   Name=Pdia4; Synonyms=Cai, Erp72;
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 [MRNA].
RX   PubMed=2295602; DOI=10.1016/s0021-9258(19)40163-4;
RA   Mazzarella R.A., Srinivasan M., Haugejorden S.M., Green M.;
RT   "ERp72, an abundant luminal endoplasmic reticulum protein, contains three
RT   copies of the active site sequences of protein disulfide isomerase.";
RL   J. Biol. Chem. 265:1094-1101(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and DBA/2J;
RC   TISSUE=Amnion, Bone marrow, Head, Ovary, and Uterus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Embryonic germ cell;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 35-638.
RC   STRAIN=BALB/cJ; TISSUE=T-cell;
RX   PubMed=3320970; DOI=10.1093/nar/15.24.10584;
RA   Gough N.M., King J.A., Dunn A.R.;
RT   "An mRNA sharing sequences with a variant granulocyte-macrophage colony
RT   stimulating factor cDNA clone.";
RL   Nucleic Acids Res. 15:10584-10584(1987).
RN   [5]
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   [6]
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   [7]
RP   CATALYTIC ACTIVITY, IDENTIFICATION IN COMPLEX WITH CRELD2; MANF AND MATN3,
RP   AND MUTAGENESIS OF CYS-87 AND CYS-551.
RX   PubMed=23956175; DOI=10.1093/hmg/ddt383;
RA   Hartley C.L., Edwards S., Mullan L., Bell P.A., Fresquet M.,
RA   Boot-Handford R.P., Briggs M.D.;
RT   "Armet/Manf and Creld2 are components of a specialized ER stress response
RT   provoked by inappropriate formation of disulphide bonds: implications for
RT   genetic skeletal diseases.";
RL   Hum. Mol. Genet. 22:5262-5275(2013).
RN   [8]
RP   STRUCTURE BY NMR OF 46-277 AND 516-638.
RG   RIKEN structural genomics initiative (RSGI);
RT   "The solution structure of thioredoxin domains of mouse protein disulfide-
RT   isomerase A4.";
RL   Submitted (SEP-2006) to the PDB data bank.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC         EC=5.3.4.1; Evidence={ECO:0000305|PubMed:23956175};
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. Component of a complex containing at least CRELD2, MANF,
CC       MATN3 and PDIA4 (PubMed:23956175). {ECO:0000269|PubMed:23956175}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:P13667}. Melanosome
CC       {ECO:0000250|UniProtKB:P13667}.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA68777.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; J05186; AAA39907.1; -; mRNA.
DR   EMBL; AK028292; BAC25863.1; -; mRNA.
DR   EMBL; AK146288; BAE27045.1; -; mRNA.
DR   EMBL; AK150566; BAE29664.1; -; mRNA.
DR   EMBL; AK161534; BAE36446.1; -; mRNA.
DR   EMBL; AK169387; BAE41134.1; -; mRNA.
DR   EMBL; BC066857; AAH66857.1; -; mRNA.
DR   EMBL; BC141078; AAI41079.1; -; mRNA.
DR   EMBL; Y00884; CAA68777.1; ALT_FRAME; mRNA.
DR   PIR; B34930; ISMSER.
DR   PIR; S06318; S06318.
DR   RefSeq; NP_033917.2; NM_009787.2.
DR   PDB; 2DJ1; NMR; -; A=46-172.
DR   PDB; 2DJ2; NMR; -; A=171-277.
DR   PDB; 2DJ3; NMR; -; A=519-638.
DR   PDBsum; 2DJ1; -.
DR   PDBsum; 2DJ2; -.
DR   PDBsum; 2DJ3; -.
DR   AlphaFoldDB; P08003; -.
DR   SMR; P08003; -.
DR   BioGRID; 198446; 34.
DR   CORUM; P08003; -.
DR   IntAct; P08003; 1.
DR   STRING; 10090.ENSMUSP00000076521; -.
DR   GlyCosmos; P08003; 1 site, No reported glycans.
DR   GlyGen; P08003; 1 site.
DR   iPTMnet; P08003; -.
DR   PhosphoSitePlus; P08003; -.
DR   SwissPalm; P08003; -.
DR   EPD; P08003; -.
DR   jPOST; P08003; -.
DR   MaxQB; P08003; -.
DR   PaxDb; 10090-ENSMUSP00000076521; -.
DR   PeptideAtlas; P08003; -.
DR   ProteomicsDB; 289334; -.
DR   Pumba; P08003; -.
DR   DNASU; 12304; -.
DR   GeneID; 12304; -.
DR   KEGG; mmu:12304; -.
DR   UCSC; uc009btf.1; mouse.
DR   AGR; MGI:104864; -.
DR   CTD; 9601; -.
DR   MGI; MGI:104864; Pdia4.
DR   eggNOG; KOG0190; Eukaryota.
DR   InParanoid; P08003; -.
DR   OrthoDB; 5399045at2759; -.
DR   PhylomeDB; P08003; -.
DR   TreeFam; TF106382; -.
DR   BioGRID-ORCS; 12304; 0 hits in 80 CRISPR screens.
DR   ChiTaRS; Pdia4; mouse.
DR   EvolutionaryTrace; P08003; -.
DR   PRO; PR:P08003; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; P08003; Protein.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005178; F:integrin binding; IPI:MGI.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; IDA:MGI.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; ISO:MGI.
DR   GO; GO:0072378; P:blood coagulation, fibrin clot formation; IMP:MGI.
DR   GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR   GO; GO:0070527; P:platelet aggregation; IMP:MGI.
DR   GO; GO:1903334; P:positive regulation of protein folding; ISO: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; 2.
DR   CDD; cd02995; PDI_a_PDI_a'_C; 1.
DR   CDD; cd03073; PDI_b'_ERp72_ERp57; 1.
DR   CDD; cd03068; PDI_b_ERp72; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 5.
DR   InterPro; IPR005788; PDI_thioredoxin-like_dom.
DR   InterPro; IPR041866; PDIA4_PDI_b.
DR   InterPro; IPR005792; Prot_disulphide_isomerase.
DR   InterPro; IPR017068; Protein_diS-isomerase_A4.
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; 3.
DR   PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1.
DR   PANTHER; PTHR18929:SF210; PROTEIN DISULFIDE-ISOMERASE A4; 1.
DR   Pfam; PF00085; Thioredoxin; 3.
DR   Pfam; PF13848; Thioredoxin_6; 1.
DR   PIRSF; PIRSF036862; Disulphide_isom_A4; 1.
DR   PRINTS; PR00421; THIOREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 5.
DR   PROSITE; PS00014; ER_TARGET; 1.
DR   PROSITE; PS00194; THIOREDOXIN_1; 3.
DR   PROSITE; PS51352; THIOREDOXIN_2; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Disulfide bond; Endoplasmic reticulum;
KW   Glycoprotein; Isomerase; Redox-active center; Reference proteome; Repeat;
KW   Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..638
FT                   /note="Protein disulfide-isomerase A4"
FT                   /id="PRO_0000034230"
FT   DOMAIN          21..162
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          162..294
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          498..629
FT                   /note="Thioredoxin 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          24..50
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           84..87
FT                   /note="CXXC"
FT                   /evidence="ECO:0000305|PubMed:23956175"
FT   MOTIF           548..551
FT                   /note="CXXC"
FT                   /evidence="ECO:0000305|PubMed:23956175"
FT   MOTIF           635..638
FT                   /note="Prevents secretion from ER"
FT   COMPBIAS        33..50
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         359
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P13667"
FT   CARBOHYD        36
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        84..87
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691,
FT                   ECO:0000269|PubMed:23956175"
FT   DISULFID        199..202
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        548..551
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691,
FT                   ECO:0000269|PubMed:23956175"
FT   MUTAGEN         87
FT                   /note="C->A: Substrate-trapping mutant."
FT                   /evidence="ECO:0000269|PubMed:23956175"
FT   MUTAGEN         551
FT                   /note="C->A: Substrate-trapping mutant."
FT                   /evidence="ECO:0000269|PubMed:23956175"
FT   CONFLICT        28
FT                   /note="H -> Q (in Ref. 1; AAA39907, 2; BAE27045 and 3;
FT                   AAI41079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        39
FT                   /note="E -> EEEE (in Ref. 2;
FT                   BAC25863/BAE41134/BAE36446/BAE29664)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        468
FT                   /note="N -> S (in Ref. 2; BAC25863)"
FT                   /evidence="ECO:0000305"
FT   STRAND          52..54
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          57..59
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   TURN            62..64
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   HELIX           65..69
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          73..79
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   HELIX           85..88
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   HELIX           91..102
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          103..106
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          109..113
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   TURN            115..117
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   HELIX           119..124
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          129..137
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          140..143
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   HELIX           150..161
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          162..164
FT                   /evidence="ECO:0007829|PDB:2DJ1"
FT   STRAND          171..173
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   TURN            177..179
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   TURN            181..183
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   HELIX           184..186
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          188..195
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   HELIX           200..218
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          219..221
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          225..229
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   TURN            230..232
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   HELIX           234..239
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          244..254
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          256..258
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   HELIX           265..277
FT                   /evidence="ECO:0007829|PDB:2DJ2"
FT   STRAND          519..522
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   TURN            525..527
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   HELIX           528..532
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   STRAND          537..543
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   HELIX           550..565
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   STRAND          568..576
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   TURN            578..580
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   STRAND          591..599
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   HELIX           619..627
FT                   /evidence="ECO:0007829|PDB:2DJ3"
FT   STRAND          628..630
FT                   /evidence="ECO:0007829|PDB:2DJ3"
SQ   SEQUENCE   638 AA;  71982 MW;  2DDE2CE80BD77F6E CRC64;
     MKLRKAWLLV LLLALTQLLA AASAGDAHED TSDTENATEE EEEEDDDDLE VKEENGVWVL
     NDGNFDNFVA DKDTVLLEFY APWCGHCKQF APEYEKIAST LKDNDPPIAV AKIDATSASM
     LASKFDVSGY PTIKILKKGQ AVDYDGSRTQ EEIVAKVREV SQPDWTPPPE VTLSLTKDNF
     DDVVNNADII LVEFYAPWCG HCKKLAPEYE KAAKELSKRS PPIPLAKVDA TEQTDLAKRF
     DVSGYPTLKI FRKGRPFDYN GPREKYGIVD YMIEQSGPPS KEILTLKQVQ EFLKDGDDVV
     IIGLFQGDGD PAYLQYQDAA NNLREDYKFH HTFSPEIAKF LKVSLGKLVL THPEKFQSKY
     EPRFHVMDVQ GSTEASAIKD YVVKHALPLV GHRKTSNDAK RYSKRPLVVV YYSVDFSFDY
     RAATQFWRNK VLEVAKDFPE YTFAIADEED YATEVKDLGL SESGEDVNAA ILDESGKKFA
     MEPEEFDSDT LREFVTAFKK GKLKPVIKSQ PVPKNNKGPV KVVVGKTFDA IVMDPKKDVL
     IEFYAPWCGH CKQLEPIYTS LGKKYKGQKD LVIAKMDATA NDITNDQYKV EGFPTIYFAP
     SGDKKNPIKF EGGNRDLEHL SKFIDEHATK RSRTKEEL
//