TXD12_HUMAN
ID TXD12_HUMAN Reviewed; 172 AA.
AC O95881; B3KQS0; Q5T1T4; Q96H50;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Thioredoxin domain-containing protein 12 {ECO:0000305|PubMed:12761212};
DE EC=1.8.4.2 {ECO:0000269|PubMed:12761212};
DE AltName: Full=Endoplasmic reticulum resident protein 18 {ECO:0000303|PubMed:12761212};
DE Short=ER protein 18 {ECO:0000303|PubMed:12761212};
DE Short=ERp18 {ECO:0000303|PubMed:12761212};
DE AltName: Full=Endoplasmic reticulum resident protein 19;
DE Short=ER protein 19;
DE Short=ERp19;
DE AltName: Full=Thioredoxin-like protein p19;
DE AltName: Full=hTLP19 {ECO:0000303|PubMed:14557066};
DE Flags: Precursor;
GN Name=TXNDC12 {ECO:0000312|HGNC:HGNC:24626};
GN Synonyms=TLP19 {ECO:0000303|PubMed:14557066}; ORFNames=UNQ713/PRO1376;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=14557066; DOI=10.1016/s0378-1119(03)00732-7;
RA Liu F., Rong Y.P., Zeng L.C., Zhang X., Han Z.G.;
RT "Isolation and characterization of a novel human thioredoxin-like gene
RT hTLP19 encoding a secretory protein.";
RL Gene 315:71-78(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Kidney, and Ovary;
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 [7]
RP PROTEIN SEQUENCE OF 27-41.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, DISULFIDE BOND, MUTAGENESIS OF CYS-66 AND CYS-69, AND MOTIF.
RX PubMed=12761212; DOI=10.1074/jbc.m304598200;
RA Alanen H.I., Williamson R.A., Howard M.J., Lappi A.-K., Jaentti H.P.,
RA Rautio S.M., Kellokumpu S., Ruddock L.W.;
RT "Functional characterization of ERp18, a new endoplasmic reticulum-located
RT thioredoxin superfamily member.";
RL J. Biol. Chem. 278:28912-28920(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP STRUCTURE BY NMR OF 24-172, AND DISULFIDE BOND.
RX PubMed=19361226; DOI=10.1021/bi9003342;
RA Rowe M.L., Ruddock L.W., Kelly G., Schmidt J.M., Williamson R.A.,
RA Howard M.J.;
RT "Solution structure and dynamics of ERp18, a small endoplasmic reticulum
RT resident oxidoreductase.";
RL Biochemistry 48:4596-4606(2009).
CC -!- FUNCTION: Protein-disulfide reductase of the endoplasmic reticulum that
CC promotes disulfide bond formation in client proteins through its thiol-
CC disulfide oxidase activity. {ECO:0000269|PubMed:12761212}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-disulfide + 2 glutathione = [protein]-dithiol +
CC glutathione disulfide; Xref=Rhea:RHEA:21064, Rhea:RHEA-COMP:10593,
CC Rhea:RHEA-COMP:10594, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.8.4.2;
CC Evidence={ECO:0000269|PubMed:12761212};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21066;
CC Evidence={ECO:0000305|PubMed:12761212};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for Asn-Arg-Cys-Ser-Gln-Gly-Ser-Cys-Trp-Asn
CC {ECO:0000269|PubMed:12761212};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:12761212};
CC -!- INTERACTION:
CC O95881; P49069: CAMLG; NbExp=5; IntAct=EBI-2564581, EBI-1748958;
CC O95881; Q92785: DPF2; NbExp=3; IntAct=EBI-2564581, EBI-359932;
CC O95881; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-2564581, EBI-3918971;
CC O95881; O95198: KLHL2; NbExp=4; IntAct=EBI-2564581, EBI-746999;
CC O95881; O43765: SGTA; NbExp=3; IntAct=EBI-2564581, EBI-347996;
CC O95881; Q96EQ0: SGTB; NbExp=6; IntAct=EBI-2564581, EBI-744081;
CC O95881; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-2564581, EBI-741480;
CC O95881; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-2564581, EBI-10173939;
CC O95881; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2564581, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138, ECO:0000269|PubMed:12761212}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:14557066}.
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DR EMBL; AF543416; AAN34781.1; -; mRNA.
DR EMBL; AF131758; AAD20035.1; -; mRNA.
DR EMBL; AY358982; AAQ89341.1; -; mRNA.
DR EMBL; AK075409; BAG52132.1; -; mRNA.
DR EMBL; AL445685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001493; AAH01493.1; -; mRNA.
DR EMBL; BC008953; AAH08953.1; -; mRNA.
DR EMBL; BC008913; AAH08913.1; -; mRNA.
DR CCDS; CCDS561.1; -.
DR RefSeq; NP_056997.1; NM_015913.3.
DR PDB; 1SEN; X-ray; 1.20 A; A=23-172.
DR PDB; 2K8V; NMR; -; A=24-172.
DR PDBsum; 1SEN; -.
DR PDBsum; 2K8V; -.
DR AlphaFoldDB; O95881; -.
DR BMRB; O95881; -.
DR SMR; O95881; -.
DR BioGRID; 119252; 111.
DR IntAct; O95881; 34.
DR MINT; O95881; -.
DR STRING; 9606.ENSP00000360688; -.
DR GlyGen; O95881; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; O95881; -.
DR PhosphoSitePlus; O95881; -.
DR SwissPalm; O95881; -.
DR BioMuta; TXNDC12; -.
DR EPD; O95881; -.
DR jPOST; O95881; -.
DR MassIVE; O95881; -.
DR MaxQB; O95881; -.
DR PaxDb; O95881; -.
DR PeptideAtlas; O95881; -.
DR PRIDE; O95881; -.
DR ProteomicsDB; 51117; -.
DR TopDownProteomics; O95881; -.
DR Antibodypedia; 46886; 142 antibodies from 20 providers.
DR DNASU; 51060; -.
DR Ensembl; ENST00000371626.9; ENSP00000360688.4; ENSG00000117862.13.
DR GeneID; 51060; -.
DR KEGG; hsa:51060; -.
DR MANE-Select; ENST00000371626.9; ENSP00000360688.4; NM_015913.4; NP_056997.1.
DR UCSC; uc001cti.5; human.
DR CTD; 51060; -.
DR DisGeNET; 51060; -.
DR GeneCards; TXNDC12; -.
DR HGNC; HGNC:24626; TXNDC12.
DR HPA; ENSG00000117862; Low tissue specificity.
DR MIM; 609448; gene.
DR neXtProt; NX_O95881; -.
DR OpenTargets; ENSG00000117862; -.
DR PharmGKB; PA142670665; -.
DR VEuPathDB; HostDB:ENSG00000117862; -.
DR eggNOG; ENOG502RXP1; Eukaryota.
DR GeneTree; ENSGT00530000063273; -.
DR HOGENOM; CLU_088048_2_0_1; -.
DR InParanoid; O95881; -.
DR OMA; DIAWVKW; -.
DR OrthoDB; 1382017at2759; -.
DR PhylomeDB; O95881; -.
DR TreeFam; TF321449; -.
DR PathwayCommons; O95881; -.
DR SignaLink; O95881; -.
DR BioGRID-ORCS; 51060; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; TXNDC12; human.
DR EvolutionaryTrace; O95881; -.
DR GeneWiki; TXNDC12; -.
DR GenomeRNAi; 51060; -.
DR Pharos; O95881; Tbio.
DR PRO; PR:O95881; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95881; protein.
DR Bgee; ENSG00000117862; Expressed in monocyte and 98 other tissues.
DR ExpressionAtlas; O95881; baseline and differential.
DR Genevisible; O95881; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0019153; F:protein-disulfide reductase (glutathione) activity; IDA:UniProtKB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:MGI.
DR CDD; cd02959; ERp19; 1.
DR InterPro; IPR037462; ERp19.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00194; THIOREDOXIN_1; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Oxidoreductase; Redox-active center;
KW Reference proteome; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 27..172
FT /note="Thioredoxin domain-containing protein 12"
FT /id="PRO_0000034189"
FT DOMAIN 27..156
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT MOTIF 169..172
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138,
FT ECO:0000305|PubMed:12761212"
FT DISULFID 66..69
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691,
FT ECO:0000269|PubMed:12761212, ECO:0000269|PubMed:19361226"
FT MUTAGEN 66
FT /note="C->S: Loss of protein-disulfide reductase
FT (glutathione) activity. Loss of the formation of disulfide
FT bonds in substrate."
FT /evidence="ECO:0000269|PubMed:12761212"
FT MUTAGEN 69
FT /note="C->S: Loss of protein-disulfide reductase
FT (glutathione) activity. Loss of the formation of disulfide
FT bonds in substrate."
FT /evidence="ECO:0000269|PubMed:12761212"
FT CONFLICT 102
FT /note="D -> H (in Ref. 6; AAH08913)"
FT /evidence="ECO:0000305"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2K8V"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:1SEN"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:1SEN"
FT HELIX 67..77
FT /evidence="ECO:0007829|PDB:1SEN"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:1SEN"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:1SEN"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:1SEN"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:1SEN"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:1SEN"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:2K8V"
FT TURN 135..139
FT /evidence="ECO:0007829|PDB:2K8V"
FT HELIX 144..158
FT /evidence="ECO:0007829|PDB:1SEN"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:1SEN"
SQ SEQUENCE 172 AA; 19206 MW; 3092E9515A7C4094 CRC64;
METRPRLGAT CLLGFSFLLL VISSDGHNGL GKGFGDHIHW RTLEDGKKEA AASGLPLMVI
IHKSWCGACK ALKPKFAEST EISELSHNFV MVNLEDEEEP KDEDFSPDGG YIPRILFLDP
SGKVHPEIIN ENGNPSYKYF YVSAEQVVQG MKEAQERLTG DAFRKKHLED EL
