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 13-FEB-2019, entry version 166. DE RecName: Full=Thioredoxin domain-containing protein 12; DE EC=1.8.4.2; DE AltName: Full=Endoplasmic reticulum resident protein 18; DE Short=ER protein 18; DE Short=ERp18; 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; DE Flags: Precursor; GN Name=TXNDC12; Synonyms=TLP19; ORFNames=UNQ713/PRO1376; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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- RT length human cDNAs encoding secretion or membrane proteins from oligo- RT capped cDNA 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RT project: 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 RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, AND MUTAGENESIS OF RP CYS-66 AND CYS-69. 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- RT located 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., RA Buerckstuemmer T., 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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., RA Ayoub D., 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 RT reticulum resident oxidoreductase."; RL Biochemistry 48:4596-4606(2009). CC -!- FUNCTION: Possesses significant protein thiol-disulfide oxidase CC 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- CC COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:29950, CC ChEBI:CHEBI:50058, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; CC EC=1.8.4.2; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=25 uM for Asn-Arg-Cys-Ser-Gln-Gly-Ser-Cys-Trp-Asn; CC pH dependence: CC Optimum pH is 6.5.; CC -!- INTERACTION: CC O95198:KLHL2; NbExp=3; IntAct=EBI-2564581, EBI-746999; CC O43765:SGTA; NbExp=3; IntAct=EBI-2564581, EBI-347996; CC Q96EQ0:SGTB; NbExp=5; IntAct=EBI-2564581, EBI-744081; CC Q9UMX0:UBQLN1; NbExp=3; IntAct=EBI-2564581, EBI-741480; CC Q9UMX0-2:UBQLN1; NbExp=3; IntAct=EBI-2564581, EBI-10173939; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen CC {ECO:0000269|PubMed:12761212}. CC -!- TISSUE SPECIFICITY: Widely expressed. CC {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_015913.3. DR UniGene; Hs.476033; -. 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 ProteinModelPortal; O95881; -. DR SMR; O95881; -. DR BioGrid; 119252; 29. DR IntAct; O95881; 12. DR STRING; 9606.ENSP00000360688; -. DR DrugBank; DB00143; Glutathione. DR iPTMnet; O95881; -. DR PhosphoSitePlus; O95881; -. DR BioMuta; TXNDC12; -. DR EPD; O95881; -. DR jPOST; O95881; -. DR MaxQB; O95881; -. DR PaxDb; O95881; -. DR PeptideAtlas; O95881; -. DR PRIDE; O95881; -. DR ProteomicsDB; 51117; -. DR TopDownProteomics; O95881; -. DR DNASU; 51060; -. DR Ensembl; ENST00000371626; ENSP00000360688; ENSG00000117862. DR GeneID; 51060; -. DR KEGG; hsa:51060; -. DR UCSC; uc001cti.5; human. DR CTD; 51060; -. DR DisGeNET; 51060; -. DR EuPathDB; HostDB:ENSG00000117862.11; -. DR GeneCards; TXNDC12; -. DR H-InvDB; HIX0116253; -. DR HGNC; HGNC:24626; TXNDC12. DR MIM; 609448; gene. DR neXtProt; NX_O95881; -. DR OpenTargets; ENSG00000117862; -. DR PharmGKB; PA142670665; -. DR eggNOG; ENOG410IWGE; Eukaryota. DR eggNOG; ENOG4111X7E; LUCA. DR GeneTree; ENSGT00530000063273; -. DR HOGENOM; HOG000231100; -. DR HOVERGEN; HBG107174; -. DR InParanoid; O95881; -. DR KO; K05360; -. DR OMA; NIHWRTL; -. DR OrthoDB; 1382017at2759; -. DR PhylomeDB; O95881; -. DR TreeFam; TF321449; -. DR ChiTaRS; TXNDC12; human. DR EvolutionaryTrace; O95881; -. DR GeneWiki; TXNDC12; -. DR GenomeRNAi; 51060; -. DR PRO; PR:O95881; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000117862; Expressed in 202 organ(s), highest expression level in metanephros. 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:MGI. DR GO; GO:0015037; F:peptide disulfide oxidoreductase activity; IDA:MGI. DR GO; GO:0019153; F:protein-disulfide reductase (glutathione) activity; IEA:UniProtKB-EC. DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro. 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; Complete proteome; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Oxidoreductase; KW Redox-active center; Reference proteome; Signal. FT SIGNAL 1 26 {ECO:0000269|PubMed:15340161}. FT CHAIN 27 172 Thioredoxin domain-containing protein 12. FT /FTId=PRO_0000034189. FT DOMAIN 27 156 Thioredoxin. {ECO:0000255|PROSITE- FT ProRule:PRU00691}. FT MOTIF 169 172 Prevents secretion from ER. FT {ECO:0000255}. FT DISULFID 66 69 Redox-active. {ECO:0000255|PROSITE- FT ProRule:PRU00691, FT ECO:0000269|PubMed:12761212, FT ECO:0000269|PubMed:19361226}. FT MUTAGEN 66 66 C->S: Loss of oxidase activity. FT {ECO:0000269|PubMed:12761212}. FT MUTAGEN 69 69 C->S: Loss of oxidase activity. FT {ECO:0000269|PubMed:12761212}. FT CONFLICT 102 102 D -> H (in Ref. 6; AAH08913). FT {ECO:0000305}. FT STRAND 33 38 {ECO:0000244|PDB:2K8V}. FT HELIX 43 53 {ECO:0000244|PDB:1SEN}. FT STRAND 57 62 {ECO:0000244|PDB:1SEN}. FT HELIX 67 77 {ECO:0000244|PDB:1SEN}. FT HELIX 80 86 {ECO:0000244|PDB:1SEN}. FT STRAND 89 95 {ECO:0000244|PDB:1SEN}. FT HELIX 96 98 {ECO:0000244|PDB:1SEN}. FT HELIX 103 105 {ECO:0000244|PDB:1SEN}. FT STRAND 112 118 {ECO:0000244|PDB:1SEN}. FT TURN 120 122 {ECO:0000244|PDB:2K8V}. FT TURN 135 139 {ECO:0000244|PDB:2K8V}. FT HELIX 144 158 {ECO:0000244|PDB:1SEN}. FT HELIX 159 161 {ECO:0000244|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 //