ID PDIA6_RAT Reviewed; 440 AA. AC Q63081; Q641Y3; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 27-MAR-2024, entry version 169. DE RecName: Full=Protein disulfide-isomerase A6; DE EC=5.3.4.1 {ECO:0000250|UniProtKB:Q15084}; DE AltName: Full=Calcium-binding protein 1; DE Short=CaBP1; DE AltName: Full=Protein disulfide isomerase P5; DE AltName: Full=Thioredoxin domain-containing protein 7; DE Flags: Precursor; GN Name=Pdia6; Synonyms=Cabp1, Txndc7; 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 [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-440. RC STRAIN=Wistar; TISSUE=Liver; RX PubMed=7876340; DOI=10.1242/jcs.107.10.2719; RA Fuellekrug J., Soennichsen B., Wuensch U., Arseven K., Van P.N., RA Soeling H.-D., Mieskes G.; RT "CaBP1, a calcium binding protein of the thioredoxin family, is a resident RT KDEL protein of the ER and not of the intermediate compartment."; RL J. Cell Sci. 107:2719-2727(1994). RN [3] RP PROTEIN SEQUENCE OF 119-132; 217-231 AND 314-322, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Kang S.U.; RL Submitted (JUL-2007) to UniProtKB. RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-428, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: May function as a chaperone that inhibits aggregation of CC misfolded proteins. Negatively regulates the unfolded protein response CC (UPR) through binding to UPR sensors such as ERN1, which in turn CC inactivates ERN1 signaling. May also regulate the UPR via the EIF2AK3 CC UPR sensor. Plays a role in platelet aggregation and activation by CC agonists such as convulxin, collagen and thrombin. CC {ECO:0000250|UniProtKB:Q15084}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.; CC EC=5.3.4.1; Evidence={ECO:0000250|UniProtKB:Q15084}; 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. Interacts with MICA on the surface of tumor cells, leading to CC MICA disulfide bond reduction which is required for its release from CC tumor cells. Interacts with ITGB3 following platelet stimulation. CC Interacts with ERN1; the interaction is direct. Interacts with EIF2AK3. CC {ECO:0000250|UniProtKB:Q15084}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen CC {ECO:0000250|UniProtKB:Q15084}. Cell membrane CC {ECO:0000250|UniProtKB:Q15084}. Melanosome CC {ECO:0000250|UniProtKB:Q15084}. CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH82063.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC082063; AAH82063.1; ALT_INIT; mRNA. DR EMBL; X79328; CAA55891.1; -; mRNA. DR PIR; S45038; S45038. DR RefSeq; NP_001004442.1; NM_001004442.1. DR AlphaFoldDB; Q63081; -. DR SMR; Q63081; -. DR BioGRID; 251898; 1. DR IntAct; Q63081; 6. DR MINT; Q63081; -. DR STRING; 10116.ENSRNOP00000064632; -. DR iPTMnet; Q63081; -. DR PhosphoSitePlus; Q63081; -. DR SwissPalm; Q63081; -. DR jPOST; Q63081; -. DR PaxDb; 10116-ENSRNOP00000064632; -. DR GeneID; 286906; -. DR KEGG; rno:286906; -. DR AGR; RGD:628688; -. DR CTD; 10130; -. DR RGD; 628688; Pdia6. DR eggNOG; KOG0191; Eukaryota. DR InParanoid; Q63081; -. DR OrthoDB; 52245at2759; -. DR PhylomeDB; Q63081; -. DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation. DR PRO; PR:Q63081; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISO:RGD. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:HGNC-UCL. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD. DR GO; GO:0005615; C:extracellular space; ISO:RGD. DR GO; GO:0042470; C:melanosome; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; TAS:RGD. DR GO; GO:0003756; F:protein disulfide isomerase activity; ISS:UniProtKB. DR GO; GO:0015035; F:protein-disulfide reductase activity; ISO:RGD. DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; ISO:RGD. DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB. DR GO; GO:0070527; P:platelet aggregation; ISS:UniProtKB. DR GO; GO:0006457; P:protein folding; TAS:RGD. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central. DR CDD; cd02983; P5_C; 1. DR CDD; cd03001; PDI_a_P5; 2. DR Gene3D; 3.40.30.10; Glutaredoxin; 2. DR InterPro; IPR005788; PDI_thioredoxin-like_dom. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR017937; Thioredoxin_CS. DR InterPro; IPR013766; Thioredoxin_domain. DR NCBIfam; TIGR01126; pdi_dom; 2. DR PANTHER; PTHR45815; PROTEIN DISULFIDE-ISOMERASE A6; 1. DR PANTHER; PTHR45815:SF3; PROTEIN DISULFIDE-ISOMERASE A6; 1. DR Pfam; PF00085; Thioredoxin; 2. DR PRINTS; PR00421; THIOREDOXIN. DR SUPFAM; SSF52833; Thioredoxin-like; 3. DR PROSITE; PS00014; ER_TARGET; 1. DR PROSITE; PS00194; THIOREDOXIN_1; 2. DR PROSITE; PS51352; THIOREDOXIN_2; 2. PE 1: Evidence at protein level; KW Calcium; Cell membrane; Chaperone; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Isomerase; Membrane; Phosphoprotein; KW Redox-active center; Reference proteome; Repeat; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000250" FT CHAIN 20..440 FT /note="Protein disulfide-isomerase A6" FT /id="PRO_0000034240" FT DOMAIN 21..133 FT /note="Thioredoxin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT DOMAIN 151..287 FT /note="Thioredoxin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT REGION 139..161 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 399..440 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 437..440 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138" FT COMPBIAS 419..440 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 55 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 58 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 190 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 193 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT SITE 56 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 57 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 118 FT /note="Lowers pKa of C-terminal Cys of first active site" FT /evidence="ECO:0000250" FT SITE 191 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 192 FT /note="Contributes to redox potential value" FT /evidence="ECO:0000250" FT SITE 256 FT /note="Lowers pKa of C-terminal Cys of second active site" FT /evidence="ECO:0000250" FT MOD_RES 129 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 156 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15084" FT MOD_RES 158 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15084" FT MOD_RES 428 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT DISULFID 55..58 FT /note="Redox-active" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT DISULFID 190..193 FT /note="Redox-active" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" SQ SEQUENCE 440 AA; 48173 MW; 8D388E4FFD743719 CRC64; MARLVLGLVS CTFFLAVSAL YSSSDDVIEL TPSNFNREVI QSDSLWLVEF YAPWCGHCQR LTPEWKKAAS ALKDVVKVGA VNADKHQSLG GQYGVQGFPT IKIFGANKNK PEDYQGGRTG EAIVDAALSA LRQLVKDRLG GRSGGYSSGK QGRGDSSSKK DVVELTDDTF DKNVLDSEDV WMVEFYAPWC GHCKNLEPEW AAAATEVKEQ TKGKVKLAAV DATVNQVLAS RYGIKGFPTI KIFQKGESPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDIAKKT CEEHQLCVVA VLPHILDTGA TGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQYELENALG IGGFGYPAMA AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG GSFPNITPRE PWDGKDGELP VEDDIDLSDV ELDDLEKDEL //