ID   PDIA6_PONAB             Reviewed;         440 AA.
AC   Q5R6T1;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 105.
DE   RecName: Full=Protein disulfide-isomerase A6;
DE            EC=5.3.4.1 {ECO:0000250|UniProtKB:Q15084};
DE   Flags: Precursor;
GN   Name=PDIA6;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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DR   EMBL; CR860403; CAH92529.1; -; mRNA.
DR   RefSeq; NP_001126483.1; NM_001133011.1.
DR   AlphaFoldDB; Q5R6T1; -.
DR   SMR; Q5R6T1; -.
DR   STRING; 9601.ENSPPYP00000014123; -.
DR   Ensembl; ENSPPYT00000045108.1; ENSPPYP00000035740.1; ENSPPYG00000012651.3.
DR   GeneID; 100173470; -.
DR   KEGG; pon:100173470; -.
DR   CTD; 10130; -.
DR   eggNOG; KOG0191; Eukaryota.
DR   GeneTree; ENSGT00940000155646; -.
DR   InParanoid; Q5R6T1; -.
DR   OrthoDB; 52245at2759; -.
DR   Proteomes; UP000001595; Chromosome 2A.
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   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   2: Evidence at transcript level;
KW   Cell membrane; Chaperone; Disulfide bond; Endoplasmic reticulum; Isomerase;
KW   Membrane; Phosphoprotein; Redox-active center; Reference proteome; Repeat;
KW   Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..440
FT                   /note="Protein disulfide-isomerase A6"
FT                   /id="PRO_0000034239"
FT   DOMAIN          20..132
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          124..287
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          139..160
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   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         428
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   440 AA;  48110 MW;  34CC8CEEED17B34C CRC64;
     MALLVLGLVS CAFFLEVNGL YSSSDDVIEL TPSNFNREVI QSDSLWLVEF YAPWCGHCQR
     LTPEWKKAAT ALKDVVKVGA VDADKHHSLG GQYGVQGFPT IKIFGSNKNR PEDYQGGRTG
     EAIVDAALSA LRQLVKDRLG GQSGGYSSGK QGRSDSSSKK DVIELTDDSF DKNVLDSEDV
     WMVEFYAPWC GHCKNLEPEW AAAASEVKEQ TKGKVKLAAV DATVNQVLAS RYGIRGFPTI
     KIFQKGESPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IISEDIAKRT CEEHQLCVVS
     VLPHILDTGA AGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQSELETALG IGGFGYPAMA
     AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG GAFPTIVERE PWDGRDGELP
     VEDDIDLSDV ELDDLGKDEL
//