PDIA6_MESAU
ID PDIA6_MESAU Reviewed; 439 AA.
AC P38660;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 25-MAY-2022, entry version 124.
DE RecName: Full=Protein disulfide-isomerase A6;
DE EC=5.3.4.1 {ECO:0000250|UniProtKB:Q15084};
DE AltName: Full=Protein disulfide isomerase P5;
DE Flags: Precursor;
GN Name=PDIA6;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 20-43.
RX PubMed=1311171; DOI=10.1042/bj2810645;
RA Chaudhuri M.M., Tonin P.N., Lewis W.H., Srinivasan P.R.;
RT "The gene for a novel protein, a member of the protein disulphide
RT isomerase/form I phosphoinositide-specific phospholipase C family, is
RT amplified in hydroxyurea-resistant cells.";
RL Biochem. J. 281:645-650(1992).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20400973; DOI=10.1038/aja.2010.19;
RA Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection antigen
RT (GP96) are unique to hamster caput epididymal spermatozoa.";
RL Asian J. Androl. 12:344-355(2010).
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 -!- TISSUE SPECIFICITY: Expressed most abundantly in lung and kidney,
CC followed by heart, liver and brain.
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
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DR EMBL; X62678; CAA44550.1; -; mRNA.
DR PIR; S19656; S19656.
DR AlphaFoldDB; P38660; -.
DR SMR; P38660; -.
DR STRING; 10036.XP_005085000.1; -.
DR eggNOG; KOG0191; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0003756; F:protein disulfide isomerase activity; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; ISS:UniProtKB.
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 Cell membrane; Chaperone; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Isomerase; Membrane; Phosphoprotein;
KW Redox-active center; Reference proteome; Repeat; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:1311171"
FT CHAIN 20..439
FT /note="Protein disulfide-isomerase A6"
FT /id="PRO_0000034237"
FT DOMAIN 20..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 141..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 436..439
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
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:0000250|UniProtKB:Q15084"
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 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15084"
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 439 AA; 48161 MW; E24CAECF5FFF5F8D CRC64;
MARLGFGLVS CTFFLAASGL YSSSDDVIEL TPSNFNREVI QSNSLWLVEF YAPWCGHCQR
LTPEWKKAAT ALKDVVKVGA VDADKHQSLG GQYGVQGFPT IKIFGANKNK PEDYQGGRTG
EAIVDAALSA LRQLVKDRLS GRSGGYSSGK QGRGDSSSKK DVIELTDDTF DKNVLDSDDV
WMVEFYAPWC GHCKNLEPEW ATAATEVKEQ TKGKVKLAAV DATVNQVLAN RYGIRGFPTI
KIFQKGEAPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDVAKKM CEEHQLCVVA
VLPHILDTGA ARNSYLEILL KLADKYKKKM WGWLWTEAGA QSELENALGI GGFGYPAMAR
INARKMKFAL LKGSFSEQGI NEFLRELSFG RASTAPVGGG SFPAITAREP WDGRDGELPV
EDDIDLSDVE LDDLEKDEL
