ID   ERP27_HUMAN             Reviewed;         273 AA.
AC   Q96DN0;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   28-JAN-2026, entry version 165.
DE   RecName: Full=Endoplasmic reticulum resident protein 27;
DE            Short=ER protein 27;
DE            Short=ERp27;
DE   AltName: Full=Inactive protein disulfide-isomerase 27 {ECO:0000305};
DE   Flags: Precursor;
GN   Name=ERP27; Synonyms=C12orf46; ORFNames=UNQ781/PRO1575;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [4]
RP   STRUCTURE BY NMR OF 26-141, FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP   WITH PDIA3, AND MUTAGENESIS OF MET-168; ILE-196; GLU-231; TRP-232 AND
RP   ASP-233.
RX   PubMed=16940051; DOI=10.1074/jbc.m604314200;
RA   Alanen H.I., Williamson R.A., Howard M.J., Hatahet F.S., Salo K.E.H.,
RA   Kauppila A., Kellokumpu S., Ruddock L.W.;
RT   "ERp27, a new non-catalytic endoplasmic reticulum-located human protein
RT   disulfide isomerase family member, interacts with ERp57.";
RL   J. Biol. Chem. 281:33727-33738(2006).
RN   [5] {ECO:0007744|PDB:4F9Z}
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 30-256, FUNCTION, AND INDUCTION.
RX   PubMed=23192347; DOI=10.1074/jbc.m112.410522;
RA   Kober F.X., Koelmel W., Kuper J., Drechsler J., Mais C., Hermanns H.M.,
RA   Schindelin H.;
RT   "The crystal structure of the protein-disulfide isomerase family member
RT   ERp27 provides insights into its substrate binding capabilities.";
RL   J. Biol. Chem. 288:2029-2039(2013).
CC   -!- FUNCTION: Specifically binds unfolded proteins and may recruit protein
CC       disulfide isomerase PDIA3 to unfolded substrates (PubMed:16940051,
CC       PubMed:23192347). Binds protein substrates via a hydrophobic pocket in
CC       the C-terminal domain (PubMed:16940051, PubMed:23192347). May play a
CC       role in the unfolded stress response (PubMed:23192347).
CC       {ECO:0000269|PubMed:16940051, ECO:0000269|PubMed:23192347}.
CC   -!- SUBUNIT: Interacts with PDIA3. {ECO:0000269|PubMed:16940051}.
CC   -!- INTERACTION:
CC       Q96DN0; Q6QNY1: BLOC1S2; NbExp=3; IntAct=EBI-953772, EBI-465872;
CC       Q96DN0; Q5U649: C12orf60; NbExp=3; IntAct=EBI-953772, EBI-10488839;
CC       Q96DN0; P29692: EEF1D; NbExp=5; IntAct=EBI-953772, EBI-358607;
CC       Q96DN0; Q08AF8: GOLGA8G; NbExp=3; IntAct=EBI-953772, EBI-10181260;
CC       Q96DN0; P42858: HTT; NbExp=3; IntAct=EBI-953772, EBI-466029;
CC       Q96DN0; Q9H944: MED20; NbExp=3; IntAct=EBI-953772, EBI-394644;
CC       Q96DN0; O43765: SGTA; NbExp=7; IntAct=EBI-953772, EBI-347996;
CC       Q96DN0; P11441: UBL4A; NbExp=3; IntAct=EBI-953772, EBI-356983;
CC       Q96DN0; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-953772, EBI-741480;
CC       Q96DN0; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-953772, EBI-10173939;
CC       Q96DN0; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-953772, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000269|PubMed:16940051}.
CC   -!- INDUCTION: Induced by ER stress. {ECO:0000269|PubMed:23192347}.
CC   -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Does not contain a CXXC active site motif indicating that it
CC       is a catalytically redox-inactive member of the protein disulfide
CC       isomerase family. {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; AY358536; AAQ88900.1; -; mRNA.
DR   EMBL; AK056677; BAB71251.1; -; mRNA.
DR   EMBL; BC030218; AAH30218.1; -; mRNA.
DR   CCDS; CCDS8670.1; -.
DR   RefSeq; NP_001287713.1; NM_001300784.1.
DR   RefSeq; NP_689534.1; NM_152321.4.
DR   PDB; 2L4C; NMR; -; A=26-141.
DR   PDB; 4F9Z; X-ray; 2.20 A; A/B/C/D/E=30-256.
DR   PDBsum; 2L4C; -.
DR   PDBsum; 4F9Z; -.
DR   AlphaFoldDB; Q96DN0; -.
DR   SMR; Q96DN0; -.
DR   BioGRID; 125733; 30.
DR   FunCoup; Q96DN0; 219.
DR   IntAct; Q96DN0; 31.
DR   MINT; Q96DN0; -.
DR   STRING; 9606.ENSP00000266397; -.
DR   GlyCosmos; Q96DN0; 1 site, No reported glycans.
DR   GlyGen; Q96DN0; 1 site.
DR   BioMuta; ERP27; -.
DR   DMDM; 74731474; -.
DR   jPOST; Q96DN0; -.
DR   MassIVE; Q96DN0; -.
DR   PaxDb; 9606-ENSP00000266397; -.
DR   PeptideAtlas; Q96DN0; -.
DR   ProteomicsDB; 76296; -.
DR   Antibodypedia; 23696; 100 antibodies from 20 providers.
DR   DNASU; 121506; -.
DR   Ensembl; ENST00000266397.7; ENSP00000266397.2; ENSG00000139055.7.
DR   GeneID; 121506; -.
DR   KEGG; hsa:121506; -.
DR   MANE-Select; ENST00000266397.7; ENSP00000266397.2; NM_152321.4; NP_689534.1.
DR   UCSC; uc001rco.4; human.
DR   AGR; HGNC:26495; -.
DR   ClinPGx; PA162385401; -.
DR   CTD; 121506; -.
DR   DisGeNET; 121506; -.
DR   GeneCards; ERP27; -.
DR   HGNC; HGNC:26495; ERP27.
DR   HPA; ENSG00000139055; Tissue enriched (pancreas).
DR   MIM; 610642; gene.
DR   OpenTargets; ENSG00000139055; -.
DR   VEuPathDB; HostDB:ENSG00000139055; -.
DR   eggNOG; KOG0191; Eukaryota.
DR   GeneTree; ENSGT00930000151058; -.
DR   HOGENOM; CLU_088451_0_0_1; -.
DR   InParanoid; Q96DN0; -.
DR   OMA; EESHGYK; -.
DR   OrthoDB; 8667660at2759; -.
DR   PAN-GO; Q96DN0; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; Q96DN0; -.
DR   BRENDA; 5.3.4.1; 2681.
DR   PathwayCommons; Q96DN0; -.
DR   SignaLink; Q96DN0; -.
DR   Agora; ENSG00000139055; -.
DR   BioGRID-ORCS; 121506; 15 hits in 1155 CRISPR screens.
DR   ChiTaRS; ERP27; human.
DR   EvolutionaryTrace; Q96DN0; -.
DR   GenomeRNAi; 121506; -.
DR   Pharos; Q96DN0; Tbio.
DR   PRO; PR:Q96DN0; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q96DN0; protein.
DR   Bgee; ENSG00000139055; Expressed in body of pancreas and 122 other cell types or tissues.
DR   ExpressionAtlas; Q96DN0; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR   GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR   CDD; cd02982; PDI_b'_family; 1.
DR   CDD; cd02981; PDI_b_family; 1.
DR   FunFam; 3.40.30.10:FF:000212; Endoplasmic reticulum resident protein 27; 1.
DR   FunFam; 3.40.30.10:FF:000232; Endoplasmic reticulum resident protein 27; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 2.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR18929:SF193; ENDOPLASMIC RETICULUM RESIDENT PROTEIN 27; 1.
DR   PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1.
DR   Pfam; PF13848; Thioredoxin_6; 1.
DR   SUPFAM; SSF52833; Thioredoxin-like; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Endoplasmic reticulum; Glycoprotein;
KW   Proteomics identification; Reference proteome; Signal;
KW   Unfolded protein response.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..273
FT                   /note="Endoplasmic reticulum resident protein 27"
FT                   /id="PRO_0000281118"
FT   DOMAIN          39..152
FT                   /note="Thioredoxin"
FT                   /evidence="ECO:0000305"
FT   REGION          230..233
FT                   /note="PDIA3-binding site"
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MOTIF           270..273
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000305|PubMed:16940051"
FT   CARBOHYD        100
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   VARIANT         52
FT                   /note="F -> L (in dbSNP:rs35030722)"
FT                   /id="VAR_052582"
FT   MUTAGEN         168
FT                   /note="M->W: Decreases somatostatin-14 binding."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MUTAGEN         196
FT                   /note="I->A,L,W: Decreases somatostatin-14 binding."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MUTAGEN         196
FT                   /note="I->W: Conserved PDIA3 binding in vivo and in vitro."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MUTAGEN         231
FT                   /note="E->K,A: Greatly reduces PDIA3 binding in vivo and in
FT                   vitro."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MUTAGEN         232
FT                   /note="W->A: Greatly reduces PDIA3 binding in vivo and in
FT                   vitro."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   MUTAGEN         233
FT                   /note="D->G: Greatly reduces PDIA3 binding in vivo and in
FT                   vitro."
FT                   /evidence="ECO:0000269|PubMed:16940051"
FT   HELIX           46..54
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          56..63
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           71..78
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   TURN            79..81
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          85..90
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           93..98
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          103..110
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   TURN            111..114
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          115..119
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           121..125
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           129..139
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          143..146
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           149..157
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          162..168
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           175..188
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   TURN            189..192
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          194..199
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           203..205
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           206..211
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           216..218
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          220..229
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   STRAND          232..235
FT                   /evidence="ECO:0007829|PDB:4F9Z"
FT   HELIX           242..253
FT                   /evidence="ECO:0007829|PDB:4F9Z"
SQ   SEQUENCE   273 AA;  30480 MW;  D47280F6F6FDE419 CRC64;
     MEAAPSRFMF LLFLLTCELA AEVAAEVEKS SDGPGAAQEP TWLTDVPAAM EFIAATEVAV
     IGFFQDLEIP AVPILHSMVQ KFPGVSFGIS TDSEVLTHYN ITGNTICLFR LVDNEQLNLE
     DEDIESIDAT KLSRFIEINS LHMVTEYNPV TVIGLFNSVI QIHLLLIMNK ASPEYEENMH
     RYQKAAKLFQ GKILFILVDS GMKENGKVIS FFKLKESQLP ALAIYQTLDD EWDTLPTAEV
     SVEHVQNFCD GFLSGKLLKE NRESEGKTPK VEL
//