PDIA6_RAT
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 03-AUG-2022, entry version 162.
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};
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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; Q63081; -.
DR PRIDE; Q63081; -.
DR GeneID; 286906; -.
DR KEGG; rno:286906; -.
DR CTD; 10130; -.
DR RGD; 628688; Pdia6.
DR eggNOG; KOG0191; Eukaryota.
DR InParanoid; Q63081; -.
DR OrthoDB; 840943at2759; -.
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 InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR044569; PDIA6-like.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR PANTHER; PTHR45815; PTHR45815; 3.
DR Pfam; PF00085; Thioredoxin; 2.
DR SUPFAM; SSF52833; SSF52833; 3.
DR TIGRFAMs; TIGR01126; pdi_dom; 2.
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
