ID   PDIA4_RAT               Reviewed;         643 AA.
AC   P38659; Q6P7S5;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2005, sequence version 2.
DT   24-JAN-2024, entry version 183.
DE   RecName: Full=Protein disulfide-isomerase A4;
DE            EC=5.3.4.1 {ECO:0000250|UniProtKB:P08003};
DE   AltName: Full=Calcium-binding protein 2;
DE            Short=CaBP2;
DE   AltName: Full=Endoplasmic reticulum resident protein 70;
DE            Short=ER protein 70;
DE            Short=ERp70;
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=Cabp2, Erp70;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar; TISSUE=Liver;
RX   PubMed=8477750; DOI=10.1111/j.1432-1033.1993.tb17821.x;
RA   Van P.N., Rupp K., Lampen A., Soeling H.-D.;
RT   "CaBP2 is a rat homolog of ERp72 with proteindisulfide isomerase
RT   activity.";
RL   Eur. J. Biochem. 213:789-795(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pituitary;
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   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   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 283-523.
RX   PubMed=19446521; DOI=10.1016/j.str.2009.02.016;
RA   Kozlov G., Maattanen P., Schrag J.D., Hura G.L., Gabrielli L., Cygler M.,
RA   Thomas D.Y., Gehring K.;
RT   "Structure of the noncatalytic domains and global fold of the protein
RT   disulfide isomerase ERp72.";
RL   Structure 17:651-659(2009).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC         EC=5.3.4.1; Evidence={ECO:0000250|UniProtKB:P08003};
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 (By similarity). {ECO:0000250|UniProtKB:P08003}.
CC   -!- INTERACTION:
CC       P38659; P24368: Ppib; NbExp=2; IntAct=EBI-917435, EBI-916926;
CC       P38659; P06882: Tg; NbExp=3; IntAct=EBI-917435, EBI-1549657;
CC       P38659; Q9VVJ7: Sep15; Xeno; NbExp=2; IntAct=EBI-917435, EBI-128899;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000250|UniProtKB:P13667}. Melanosome
CC       {ECO:0000250|UniProtKB:P13667}.
CC   -!- INDUCTION: Upon glucose starvation, as well as treatment with
CC       tunicamycin.
CC   -!- PTM: O-glycosylated.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000305}.
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DR   EMBL; M86870; AAA19217.1; -; mRNA.
DR   EMBL; BC061535; AAH61535.1; -; mRNA.
DR   PIR; S32476; S32476.
DR   RefSeq; NP_446301.1; NM_053849.1.
DR   PDB; 3EC3; X-ray; 1.92 A; A/B=283-523.
DR   PDBsum; 3EC3; -.
DR   AlphaFoldDB; P38659; -.
DR   SMR; P38659; -.
DR   BioGRID; 250512; 5.
DR   IntAct; P38659; 11.
DR   STRING; 10116.ENSRNOP00000008728; -.
DR   GlyGen; P38659; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P38659; -.
DR   PhosphoSitePlus; P38659; -.
DR   jPOST; P38659; -.
DR   PaxDb; 10116-ENSRNOP00000008728; -.
DR   Ensembl; ENSRNOT00055044952; ENSRNOP00055036851; ENSRNOG00055026029.
DR   Ensembl; ENSRNOT00060051427; ENSRNOP00060042781; ENSRNOG00060029601.
DR   Ensembl; ENSRNOT00065025411; ENSRNOP00065019935; ENSRNOG00065015319.
DR   GeneID; 116598; -.
DR   KEGG; rno:116598; -.
DR   UCSC; RGD:619835; rat.
DR   AGR; RGD:619835; -.
DR   CTD; 9601; -.
DR   RGD; 619835; Pdia4.
DR   eggNOG; KOG0190; Eukaryota.
DR   InParanoid; P38659; -.
DR   OrthoDB; 5399045at2759; -.
DR   PhylomeDB; P38659; -.
DR   BRENDA; 5.3.4.1; 5301.
DR   EvolutionaryTrace; P38659; -.
DR   PRO; PR:P38659; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0009986; C:cell surface; ISO:RGD.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISO:RGD.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; ISO:RGD.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005178; F:integrin binding; ISO:RGD.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; IDA:UniProtKB.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; ISO:RGD.
DR   GO; GO:0072378; P:blood coagulation, fibrin clot formation; ISO:RGD.
DR   GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR   GO; GO:0070527; P:platelet aggregation; ISO:RGD.
DR   GO; GO:1903334; P:positive regulation of protein folding; IDA:RGD.
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; Calcium; 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..643
FT                   /note="Protein disulfide-isomerase A4"
FT                   /id="PRO_0000034231"
FT   DOMAIN          21..167
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          167..299
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          503..634
FT                   /note="Thioredoxin 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          24..58
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           89..92
FT                   /note="CXXC"
FT                   /evidence="ECO:0000250|UniProtKB:P08003"
FT   MOTIF           553..556
FT                   /note="CXXC"
FT                   /evidence="ECO:0000250|UniProtKB:P08003"
FT   MOTIF           640..643
FT                   /note="Prevents secretion from ER"
FT   COMPBIAS        32..57
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         364
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P13667"
FT   DISULFID        89..92
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250|UniProtKB:P08003,
FT                   ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        204..207
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        553..556
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250|UniProtKB:P08003,
FT                   ECO:0000255|PROSITE-ProRule:PRU00691"
FT   CONFLICT        43
FT                   /note="D -> E (in Ref. 1; AAA19217)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        391
FT                   /note="A -> D (in Ref. 1; AAA19217)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        497
FT                   /note="Q -> R (in Ref. 1; AAA19217)"
FT                   /evidence="ECO:0000305"
FT   STRAND          284..287
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           291..300
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          305..309
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           316..328
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   TURN            329..331
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          334..337
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           340..346
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          350..356
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           359..361
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          370..373
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           380..390
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          395..398
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   TURN            400..402
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           403..406
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          409..417
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   TURN            423..425
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           426..440
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          446..452
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   TURN            453..456
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           457..462
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          473..477
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   STRAND          483..485
FT                   /evidence="ECO:0007829|PDB:3EC3"
FT   HELIX           493..504
FT                   /evidence="ECO:0007829|PDB:3EC3"
SQ   SEQUENCE   643 AA;  72720 MW;  C5BC8536834543ED CRC64;
     MKLRKAWLLV LLLALTQLLA AASAEDAHED ASDSENPIED DDDEEEDEED EDDLEVKEEN
     GVWVLNDENF DNFVADKDTV LLEFYAPWCG HCKQFAPEYE KIASTLKDND PPIAVAKIDA
     TSASMLASKF DVSGYPTIKI LKKGQAVDYD GSRTQEEIVA KVREVSQPDW TPPPEVTLTL
     TKENFDDVVN NADIILVEFY APWCGHCKKL APEYEKAAKE LSKRSPPIPL AKVDATEQTD
     LAKRFDVSGY PTLKIFRKGR PFDYNGPREK YGIVDYMVEQ SGPPSKEILT LKQVQEFLKD
     GDDVVILGVF QGVGDPGYLQ YQDAANTLRE DYKFHHTFST EIAKFLKVSL GKLVLMQPEK
     FQSKYEPRMH VMDVQGSTEA SAIKDYVVKH ALPLVGHRKT SNDAKRYSKR PLVVVYYSVD
     FSFDYRTATQ FWRNKVLEVA KDFPEYTFAI ADEEDYATEV KDLGLSESGE DVNAAILDES
     GKKFAMEPEE FDSDALQEFV MAFKKGKLKP VIKSQPVPKN NKGPVRVVVG KTFDAIVMDP
     KKDVLIEFYA PWCGHCKQLE PVYTSLGKKY KGQKDLVIAK MDATANDITN DRYKVEGFPT
     IYFAPSGDKK NPIKFEGGNR DLEHLSKFID EHATKRSRTK EEL
//