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 10-JUN-2026, entry version 202. 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}. 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; 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_015913.4. 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; 147. DR FunCoup; O95881; 1548. DR IntAct; O95881; 42. DR MINT; O95881; -. DR STRING; 9606.ENSP00000360688; -. DR GlyCosmos; O95881; 1 site, 2 glycans. DR GlyGen; O95881; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; O95881; -. DR PhosphoSitePlus; O95881; -. DR SwissPalm; O95881; -. DR BioMuta; TXNDC12; -. DR jPOST; O95881; -. DR MassIVE; O95881; -. DR PaxDb; 9606-ENSP00000360688; -. DR PeptideAtlas; O95881; -. DR ProteomicsDB; 51117; -. DR Pumba; O95881; -. DR TopDownProteomics; O95881; -. DR Antibodypedia; 46886; 147 antibodies from 21 providers. DR DNASU; 51060; -. DR Ensembl; ENST00000371626.9; ENSP00000360688.4; ENSG00000117862.15. DR Ensembl; ENST00000715260.1; ENSP00000520430.1; ENSG00000117862.15. 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 AGR; HGNC:24626; -. DR ClinPGx; PA142670665; -. 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 OpenTargets; ENSG00000117862; -. DR VEuPathDB; HostDB:ENSG00000117862; -. DR eggNOG; ENOG502RXP1; Eukaryota. DR GeneTree; ENSGT00530000063273; -. DR HOGENOM; CLU_088048_2_0_1; -. DR InParanoid; O95881; -. DR OMA; SEHFVMV; -. DR OrthoDB; 262308at2759; -. DR PAN-GO; O95881; 1 GO annotation based on evolutionary models. DR PhylomeDB; O95881; -. DR PathwayCommons; O95881; -. DR SignaLink; O95881; -. DR Agora; ENSG00000117862; -. DR BioGRID-ORCS; 51060; 12 hits in 1157 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 100 other cell types or tissues. DR ExpressionAtlas; O95881; baseline and differential. 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:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:MGI. DR CDD; cd02959; ERp19; 1. DR FunFam; 3.40.30.10:FF:000099; thioredoxin domain-containing protein 12; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR051099; AGR/TXD. DR InterPro; IPR037462; ERp19. DR InterPro; IPR012336; Thioredoxin-like_fold. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR017937; Thioredoxin_CS. DR InterPro; IPR013766; Thioredoxin_domain. DR PANTHER; PTHR15337; ANTERIOR GRADIENT PROTEIN-RELATED; 1. DR PANTHER; PTHR15337:SF10; THIOREDOXIN DOMAIN-CONTAINING PROTEIN 12; 1. DR Pfam; PF13899; Thioredoxin_7; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 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; Proteomics identification; KW Redox-active center; 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 //