PDIA4_MOUSE
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 25-MAY-2022, entry version 194.
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, 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 [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; 33.
DR CORUM; P08003; -.
DR STRING; 10090.ENSMUSP00000076521; -.
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; P08003; -.
DR PeptideAtlas; P08003; -.
DR PRIDE; P08003; -.
DR ProteomicsDB; 289334; -.
DR DNASU; 12304; -.
DR GeneID; 12304; -.
DR KEGG; mmu:12304; -.
DR UCSC; uc009btf.1; mouse.
DR CTD; 9601; -.
DR MGI; MGI:104864; Pdia4.
DR eggNOG; KOG0190; Eukaryota.
DR InParanoid; P08003; -.
DR OrthoDB; 462118at2759; -.
DR PhylomeDB; P08003; -.
DR TreeFam; TF106382; -.
DR BioGRID-ORCS; 12304; 0 hits in 75 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:0003756; F:protein disulfide isomerase activity; ISS:UniProtKB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISO:MGI.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
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; cd03068; PDI_b_ERp72; 1.
DR InterPro; IPR005788; Disulphide_isomerase.
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 Pfam; PF00085; Thioredoxin; 3.
DR PIRSF; PIRSF036862; Disulphide_isom_A4; 1.
DR SUPFAM; SSF52833; SSF52833; 5.
DR TIGRFAMs; TIGR01130; ER_PDI_fam; 1.
DR TIGRFAMs; TIGR01126; pdi_dom; 3.
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; BAC25863/BAE41134/BAE36446/
FT 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
