ID TRXR1_HUMAN Reviewed; 649 AA. AC Q16881; B7Z1F4; B7Z3Y8; B7Z904; E9PMY9; F5H780; Q6FI31; Q6VB40; Q6VB41; AC Q6VB42; Q6VBP2; Q6VBP3; Q6VBP4; Q6VBP5; Q6VBP9; Q6VBQ0; Q6YNQ1; Q76P53; AC Q7LA96; Q8WVC8; Q99475; Q9UES8; Q9UH79; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 3. DT 27-MAR-2024, entry version 239. DE RecName: Full=Thioredoxin reductase 1, cytoplasmic {ECO:0000305}; DE Short=TR; DE EC=1.8.1.9 {ECO:0000269|PubMed:8577704}; DE AltName: Full=Gene associated with retinoic and interferon-induced mortality 12 protein; DE Short=GRIM-12; DE Short=Gene associated with retinoic and IFN-induced mortality 12 protein; DE AltName: Full=KM-102-derived reductase-like factor; DE AltName: Full=Peroxidase TXNRD1 {ECO:0000305|PubMed:10849437}; DE EC=1.11.1.2 {ECO:0000269|PubMed:10849437}; DE AltName: Full=Thioredoxin reductase TR1; GN Name=TXNRD1 {ECO:0000312|HGNC:HGNC:12437}; Synonyms=GRIM12, KDRF; 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] (ISOFORM 5), PROTEIN SEQUENCE OF 153-161; RP 307-315 AND 585-607, AND VARIANT GLY-365. RC TISSUE=Placenta; RX PubMed=7589432; DOI=10.1016/0014-5793(95)01003-w; RA Gasdaska P.Y., Gasdaska J.R., Cochran S., Powis G.; RT "Cloning and sequencing of a human thioredoxin reductase."; RL FEBS Lett. 373:5-9(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), PROTEIN SEQUENCE OF 122-127 AND RP 147-151, AND TISSUE SPECIFICITY. RC TISSUE=Bone marrow stroma; RX PubMed=8999974; DOI=10.1074/jbc.272.4.2570; RA Koishi R., Kawashima I., Yoshimura C., Sugawara M., Serizawa N.; RT "Cloning and characterization of a novel oxidoreductase KDRF from a human RT bone marrow-derived stromal cell line KM-102."; RL J. Biol. Chem. 272:2570-2577(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, AND INDUCTION. RC TISSUE=Mammary carcinoma; RX PubMed=9774665; DOI=10.1128/mcb.18.11.6493; RA Hofman E.R., Boyanapalli M., Lindner D.J., Weihua X., Hassel B.A., RA Jagus R., Gutierrez P.L., Kalvakolanu D.V.; RT "Thioredoxin reductase mediates cell death effects of the combination of RT beta interferon and retinoic acid."; RL Mol. Cell. Biol. 18:6493-6504(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [MRNA] RP (ISOFORMS 2; 3; 4 AND 5), AND VARIANT GLY-365. RC TISSUE=Mammary gland, Ovary, Testis, and Thymus; RX PubMed=14980707; DOI=10.1016/j.freeradbiomed.2003.12.004; RA Rundloef A.-K., Janard M., Miranda-Vizuete A., Arner E.S.; RT "Evidence for intriguingly complex transcription of human thioredoxin RT reductase 1."; RL Free Radic. Biol. Med. 36:641-656(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Schuetze N., Bachthaler M., Lechner A., Koehrle J., Jakob F.; RT "Identification by ddPCR of thioredoxin reductase as a vitamin D regulated RT gene in human osteoblasts."; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RC TISSUE=Brain; RA Xu L., Dai R., Xu J.Y.; RT "Cloning and sequencing of thioredoxin reductase gene from human brain."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). RC TISSUE=Astrocyte, Thalamus, and Trachea; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION. RC TISSUE=Trachea; RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). 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 [14] RP PROTEIN SEQUENCE OF 307-316; 449-456; 466-476 AND 638-649, BLOCKAGE OF RP N-TERMINUS, SELENOCYSTEINE AT SEC-648, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=8650234; DOI=10.1073/pnas.93.12.6146; RA Gladyshev V.N., Jeang K.-T., Stadtman T.C.; RT "Selenocysteine, identified as the penultimate C-terminal residue in human RT T-cell thioredoxin reductase, corresponds to TGA in the human placental RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 93:6146-6151(1996). RN [15] RP FUNCTION, HOMODIMERIZATION, CHARACTERIZATION, PRESENCE OF SELENOCYSTEINE, RP COFACTOR, AND CATALYTIC ACTIVITY. RX PubMed=8577704; DOI=10.1073/pnas.93.3.1006; RA Tamura T., Stadtman T.C.; RT "A new selenoprotein from human lung adenocarcinoma cells: purification, RT properties, and thioredoxin reductase activity."; RL Proc. Natl. Acad. Sci. U.S.A. 93:1006-1011(1996). RN [16] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY. RX PubMed=10849437; DOI=10.1074/jbc.m000690200; RA Zhong L., Holmgren A.; RT "Essential role of selenium in the catalytic activities of mammalian RT thioredoxin reductase revealed by characterization of recombinant enzymes RT with selenocysteine mutations."; RL J. Biol. Chem. 275:18121-18128(2000). RN [17] RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6), AND DOMAIN. RX PubMed=15379556; DOI=10.1021/bi048478t; RA Su D., Gladyshev V.N.; RT "Alternative splicing involving the thioredoxin reductase module in RT mammals: a glutaredoxin-containing thioredoxin reductase 1."; RL Biochemistry 43:12177-12188(2004). RN [18] RP FUNCTION, INTERACTION WITH ESR1 AND ESR2, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY (ISOFORM 4). RX PubMed=15199063; DOI=10.1074/jbc.m402753200; RA Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A., RA Spyrou G.; RT "An alternative splicing variant of the selenoprotein thioredoxin reductase RT is a modulator of estrogen signaling."; RL J. Biol. Chem. 279:38721-38729(2004). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-281, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [20] RP INTERACTION WITH HERC5, AND ISGYLATION. RX PubMed=16815975; DOI=10.1073/pnas.0600397103; RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.; RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I RT IFN-induced ISGylation of protein targets."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(2006). RN [21] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION (ISOFORM 1). RX PubMed=18042542; DOI=10.1074/jbc.m708939200; RA Dammeyer P., Damdimopoulos A.E., Nordman T., Jimenez A., RA Miranda-Vizuete A., Arner E.S.J.; RT "Induction of cell membrane protrusions by the N-terminal glutaredoxin RT domain of a rare splice variant of human thioredoxin reductase 1."; RL J. Biol. Chem. 283:2814-2821(2008). RN [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 5), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [24] 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 [25] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 5), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [26] {ECO:0007744|PDB:2J3N} RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) (ISOFORM 5) IN COMPLEX WITH FAD AND RP NADPH, COFACTOR, AND SUBUNIT. RX PubMed=17512005; DOI=10.1016/j.jmb.2007.04.044; RA Fritz-Wolf K., Urig S., Becker K.; RT "The structure of human thioredoxin reductase 1 provides insights into C- RT terminal rearrangements during catalysis."; RL J. Mol. Biol. 370:116-127(2007). CC -!- FUNCTION: Reduces disulfideprotein thioredoxin (Trx) to its dithiol- CC containing form (PubMed:8577704). Homodimeric flavoprotein involved in CC the regulation of cellular redox reactions, growth and differentiation. CC Contains a selenocysteine residue at the C-terminal active site that is CC essential for catalysis (Probable). Also has reductase activity on CC hydrogen peroxide (H2O2) (PubMed:10849437). CC {ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:8577704, CC ECO:0000305|PubMed:17512005}. CC -!- FUNCTION: [Isoform 1]: Induces actin and tubulin polymerization, CC leading to formation of cell membrane protrusions. CC {ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704}. CC -!- FUNCTION: [Isoform 4]: Enhances the transcriptional activity of CC estrogen receptors ESR1 and ESR2. {ECO:0000269|PubMed:15199063}. CC -!- FUNCTION: [Isoform 5]: Enhances the transcriptional activity of the CC estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death CC induced by a combination of interferon-beta and retinoic acid CC (PubMed:9774665). {ECO:0000269|PubMed:15199063, CC ECO:0000269|PubMed:9774665}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + CC H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA- CC COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9; CC Evidence={ECO:0000269|PubMed:8577704}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347; CC Evidence={ECO:0000305|PubMed:8577704}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + H2O2 + NADPH = 2 H2O + NADP(+); Xref=Rhea:RHEA:15173, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.11.1.2; CC Evidence={ECO:0000269|PubMed:10849437}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15174; CC Evidence={ECO:0000305|PubMed:10849437}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:17512005, CC ECO:0000269|PubMed:8577704}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.5 mM for H202 {ECO:0000269|PubMed:10849437}; CC Note=kcat is 100 min(-1) with H2O2 as substrate. CC {ECO:0000269|PubMed:10849437}; CC -!- SUBUNIT: Homodimer (PubMed:17512005, PubMed:8577704). Interacts with CC HERC5. {ECO:0000269|PubMed:16815975, ECO:0000269|PubMed:17512005, CC ECO:0000269|PubMed:8577704}. CC -!- SUBUNIT: [Isoform 4]: Interacts with ESR1 and ESR2. CC {ECO:0000269|PubMed:16815975}. CC -!- INTERACTION: CC Q16881; Q03135: CAV1; NbExp=4; IntAct=EBI-716617, EBI-603614; CC Q16881-4; P03372: ESR1; NbExp=4; IntAct=EBI-9080335, EBI-78473; CC Q16881-4; Q92731: ESR2; NbExp=3; IntAct=EBI-9080335, EBI-78505; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:18042542}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm CC {ECO:0000269|PubMed:15199063}. Nucleus {ECO:0000269|PubMed:15199063}. CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm CC {ECO:0000269|PubMed:15199063}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=V, TXNRD1_v3 {ECO:0000303|PubMed:18042542}; CC IsoId=Q16881-1; Sequence=Displayed; CC Name=2; Synonyms=II, TXNRD1_v4; CC IsoId=Q16881-2; Sequence=VSP_031560, VSP_031565; CC Name=3; Synonyms=III, TXNRD1_v5; CC IsoId=Q16881-3; Sequence=VSP_031562, VSP_031563; CC Name=4; Synonyms=IV, TXNRD1_v2, TrxR1b {ECO:0000303|PubMed:15199063}; CC IsoId=Q16881-4; Sequence=VSP_031561, VSP_031564; CC Name=5; Synonyms=I, TXNRD1_v1, TrxR1a {ECO:0000303|PubMed:15199063}; CC IsoId=Q16881-5; Sequence=VSP_031558; CC Name=6; Synonyms=VI; CC IsoId=Q16881-6; Sequence=VSP_031559; CC Name=7; CC IsoId=Q16881-7; Sequence=VSP_053819; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed predominantly in Leydig CC cells (at protein level). Also expressed in ovary, spleen, heart, CC liver, kidney and pancreas and in a number of cancer cell lines. CC {ECO:0000269|PubMed:18042542}. CC -!- TISSUE SPECIFICITY: [Isoform 4]: Widely expressed with highest levels CC in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. CC {ECO:0000269|PubMed:8999974}. CC -!- INDUCTION: [Isoform 1]: Induced by estradiol or testosterone in HeLa CC cells. {ECO:0000269|PubMed:18042542}. CC -!- INDUCTION: [Isoform 5]: Induced by a combination of interferon-beta and CC retinoic acid (at protein level). {ECO:0000269|PubMed:9774665}. CC -!- DOMAIN: [Isoform 1]: The N-terminal glutaredoxin domain does not CC contain the C-P-Y-C redox-active motif normally found in glutaredoxins CC and has been found to be inactive in classical glutaredoxin assays. CC {ECO:0000269|PubMed:15379556}. CC -!- PTM: [Isoform 5]: The N-terminus is blocked. CC -!- PTM: ISGylated. {ECO:0000305|PubMed:16815975}. CC -!- MISCELLANEOUS: The thioredoxin reductase active site is a redox-active CC disulfide bond. The selenocysteine residue is also essential for CC catalytic activity. {ECO:0000250|UniProtKB:O89049}. CC -!- MISCELLANEOUS: [Isoform 1]: Minor isoform. CC {ECO:0000269|PubMed:18042542}. CC -!- MISCELLANEOUS: [Isoform 5]: Major isoform. The N-terminus of the CC sequence is processed into a mature form that lacks residues Met-151 CC and Asn-152 at the N-terminus. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide CC oxidoreductase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB35418.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAC69621.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAF15900.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAV38446.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAZ67916.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA13674.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAH11490.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAH12374.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAH14140.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA04503.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA62629.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=CAG38744.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=EAW97745.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/txnrd1/"; 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; X91247; CAA62629.1; ALT_SEQ; mRNA. DR EMBL; S79851; AAB35418.1; ALT_SEQ; mRNA. DR EMBL; D88687; BAA13674.1; ALT_SEQ; mRNA. DR EMBL; AF077367; AAC69621.1; ALT_SEQ; mRNA. DR EMBL; AY057105; AAL15432.1; -; mRNA. DR EMBL; AY344081; AAQ62461.1; -; mRNA. DR EMBL; AY344083; AAQ62462.1; -; mRNA. DR EMBL; AY344084; AAQ62463.1; -; mRNA. DR EMBL; AY344086; AAQ62464.1; -; mRNA. DR EMBL; AY344087; AAQ62465.1; -; mRNA. DR EMBL; AY344089; AAQ62466.1; -; mRNA. DR EMBL; AY344092; AAQ62467.1; -; mRNA. DR EMBL; AY344093; AAQ62468.1; -; mRNA. DR EMBL; AY344095; AAQ62469.1; -; mRNA. DR EMBL; AY344096; AAQ62470.1; -; mRNA. DR EMBL; AY344670; AAQ62471.1; -; mRNA. DR EMBL; AY344673; AAQ62472.1; -; mRNA. DR EMBL; AY344679; AAQ62473.1; -; mRNA. DR EMBL; AJ001050; CAA04503.1; ALT_SEQ; mRNA. DR EMBL; AF208018; AAF15900.1; ALT_SEQ; mRNA. DR EMBL; AK293322; BAH11490.1; ALT_SEQ; mRNA. DR EMBL; AK296495; BAH12374.1; ALT_SEQ; mRNA. DR EMBL; AK304241; BAH14140.1; ALT_SEQ; mRNA. DR EMBL; CR536506; CAG38744.1; ALT_SEQ; mRNA. DR EMBL; BT019640; AAV38446.1; ALT_SEQ; mRNA. DR EMBL; DQ157758; AAZ67916.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC089983; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090107; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97745.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC018122; AAH18122.2; -; mRNA. DR CCDS; CCDS53820.1; -. [Q16881-1] DR CCDS; CCDS53821.1; -. [Q16881-4] DR CCDS; CCDS53823.1; -. [Q16881-5] DR CCDS; CCDS58274.1; -. [Q16881-7] DR PIR; S66677; S66677. DR RefSeq; NP_001087240.1; NM_001093771.2. [Q16881-1] DR RefSeq; NP_001248374.1; NM_001261445.1. DR RefSeq; NP_001248375.1; NM_001261446.1. [Q16881-7] DR RefSeq; NP_003321.3; NM_003330.3. [Q16881-4] DR RefSeq; NP_877393.1; NM_182729.2. [Q16881-5] DR RefSeq; NP_877419.1; NM_182742.2. [Q16881-5] DR RefSeq; NP_877420.1; NM_182743.2. [Q16881-5] DR PDB; 2CFY; X-ray; 2.70 A; A/B/C/D/E/F=151-647. DR PDB; 2J3N; X-ray; 2.80 A; A/B/C/D/E/F=151-647. DR PDB; 2ZZ0; X-ray; 2.80 A; A/B/C/D=150-647. DR PDB; 2ZZB; X-ray; 3.20 A; A/B/C/D=150-647. DR PDB; 2ZZC; X-ray; 2.60 A; A/B/C/D=150-647. DR PDB; 3QFA; X-ray; 2.20 A; A/B=151-649. DR PDB; 3QFB; X-ray; 2.60 A; A/B=151-649. DR PDB; 7X1R; EM; 3.90 A; A/B=152-649. DR PDBsum; 2CFY; -. DR PDBsum; 2J3N; -. DR PDBsum; 2ZZ0; -. DR PDBsum; 2ZZB; -. DR PDBsum; 2ZZC; -. DR PDBsum; 3QFA; -. DR PDBsum; 3QFB; -. DR PDBsum; 7X1R; -. DR EMDB; EMD-32947; -. DR SMR; Q16881; -. DR BioGRID; 113147; 104. DR IntAct; Q16881; 19. DR MINT; Q16881; -. DR STRING; 9606.ENSP00000434516; -. DR BindingDB; Q16881; -. DR ChEMBL; CHEMBL1927; -. DR DrugBank; DB01169; Arsenic trioxide. DR DrugBank; DB00126; Ascorbic acid. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB04106; Fotemustine. DR DrugBank; DB05428; Motexafin gadolinium. DR DrugBank; DB02338; NADPH. DR DrugBank; DB05448; PX-12. DR DrugBank; DB11127; Selenious acid. DR DrugBank; DB11135; Selenium. DR DrugBank; DB03566; Spermidine. DR DrugCentral; Q16881; -. DR GlyGen; Q16881; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q16881; -. DR MetOSite; Q16881; -. DR PhosphoSitePlus; Q16881; -. DR SwissPalm; Q16881; -. DR BioMuta; TXNRD1; -. DR DMDM; 172046253; -. DR REPRODUCTION-2DPAGE; IPI00554786; -. DR EPD; Q16881; -. DR jPOST; Q16881; -. DR MassIVE; Q16881; -. DR MaxQB; Q16881; -. DR PaxDb; 9606-ENSP00000434516; -. DR PeptideAtlas; Q16881; -. DR ProteomicsDB; 22254; -. DR ProteomicsDB; 27407; -. DR ProteomicsDB; 61119; -. [Q16881-1] DR ProteomicsDB; 61120; -. [Q16881-2] DR ProteomicsDB; 61121; -. [Q16881-3] DR ProteomicsDB; 61122; -. [Q16881-4] DR ProteomicsDB; 61123; -. [Q16881-5] DR ProteomicsDB; 61124; -. [Q16881-6] DR Pumba; Q16881; -. DR Antibodypedia; 3897; 522 antibodies from 43 providers. DR DNASU; 7296; -. DR Ensembl; ENST00000503506.6; ENSP00000421934.2; ENSG00000198431.18. [Q16881-5] DR Ensembl; ENST00000524698.5; ENSP00000433425.1; ENSG00000198431.18. [Q16881-5] DR Ensembl; ENST00000525566.6; ENSP00000434516.1; ENSG00000198431.18. [Q16881-1] DR Ensembl; ENST00000526390.5; ENSP00000435123.1; ENSG00000198431.18. [Q16881-2] DR Ensembl; ENST00000526691.5; ENSP00000435929.1; ENSG00000198431.18. [Q16881-4] DR Ensembl; ENST00000526950.2; ENSP00000432812.2; ENSG00000198431.18. [Q16881-6] DR Ensembl; ENST00000529546.5; ENSP00000434919.1; ENSG00000198431.18. [Q16881-7] DR GeneID; 7296; -. DR KEGG; hsa:7296; -. DR MANE-Select; ENST00000525566.6; ENSP00000434516.1; NM_001093771.3; NP_001087240.1. DR UCSC; uc010swp.4; human. [Q16881-1] DR AGR; HGNC:12437; -. DR CTD; 7296; -. DR DisGeNET; 7296; -. DR GeneCards; TXNRD1; -. DR HGNC; HGNC:12437; TXNRD1. DR HPA; ENSG00000198431; Low tissue specificity. DR MIM; 601112; gene. DR neXtProt; NX_Q16881; -. DR OpenTargets; ENSG00000198431; -. DR PharmGKB; PA37093; -. DR VEuPathDB; HostDB:ENSG00000198431; -. DR eggNOG; KOG1752; Eukaryota. DR eggNOG; KOG4716; Eukaryota. DR GeneTree; ENSGT00940000160180; -. DR HOGENOM; CLU_016755_2_4_1; -. DR InParanoid; Q16881; -. DR OrthoDB; 5473641at2759; -. DR PhylomeDB; Q16881; -. DR TreeFam; TF314782; -. DR BRENDA; 1.8.1.9; 2681. DR PathwayCommons; Q16881; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2408550; Metabolism of ingested H2SeO4 and H2SeO3 into H2Se. DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species. DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates. DR Reactome; R-HSA-5263617; Metabolism of ingested MeSeO2H into MeSeH. DR Reactome; R-HSA-5336415; Uptake and function of diphtheria toxin. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-9818027; NFE2L2 regulating anti-oxidant/detoxification enzymes. DR SignaLink; Q16881; -. DR BioGRID-ORCS; 7296; 340 hits in 1183 CRISPR screens. DR ChiTaRS; TXNRD1; human. DR EvolutionaryTrace; Q16881; -. DR GeneWiki; TXNRD1; -. DR GenomeRNAi; 7296; -. DR Pharos; Q16881; Tclin. DR PRO; PR:Q16881; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q16881; Protein. DR Bgee; ENSG00000198431; Expressed in stromal cell of endometrium and 214 other cell types or tissues. DR ExpressionAtlas; Q16881; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0050137; F:NADPH peroxidase activity; IDA:UniProtKB. DR GO; GO:0004791; F:thioredoxin-disulfide reductase (NADP) activity; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central. DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR CDD; cd03419; GRX_GRXh_1_2_like; 1. DR Gene3D; 3.30.390.30; -; 1. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR023753; FAD/NAD-binding_dom. DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf. DR InterPro; IPR002109; Glutaredoxin. DR InterPro; IPR046952; GSHR/TRXR-like. DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer. DR InterPro; IPR012999; Pyr_OxRdtase_I_AS. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase. DR NCBIfam; TIGR01438; TGR; 1. DR PANTHER; PTHR42737; GLUTATHIONE REDUCTASE; 1. DR PANTHER; PTHR42737:SF8; THIOREDOXIN REDUCTASE 1; 1. DR Pfam; PF00462; Glutaredoxin; 1. DR Pfam; PF07992; Pyr_redox_2; 1. DR Pfam; PF02852; Pyr_redox_dim; 1. DR PRINTS; PR00368; FADPNR. DR PRINTS; PR00411; PNDRDTASEI. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS51354; GLUTAREDOXIN_2; 1. DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1. DR Genevisible; Q16881; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Electron transport; FAD; KW Flavoprotein; NADP; Nucleus; Oxidoreductase; Phosphoprotein; KW Redox-active center; Reference proteome; Selenocysteine; Transport; KW Ubl conjugation. FT CHAIN 1..649 FT /note="Thioredoxin reductase 1, cytoplasmic" FT /id="PRO_0000030286" FT DOMAIN 56..156 FT /note="Glutaredoxin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686" FT REGION 1..49 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 145..149 FT /note="Required for interaction with ESR1 and ESR2" FT /evidence="ECO:0000269|PubMed:15199063" FT COMPBIAS 21..39 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 622 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 172..173 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 192..193 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 208..209 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 213..217 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 281..282 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 311 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0007744|PDB:2J3N" FT BINDING 316 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 348..354 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 350 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0007744|PDB:2ZZ0, ECO:0007744|PDB:2ZZB, FT ECO:0007744|PDB:3QFA" FT BINDING 371..372 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 376..378 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 376 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O89049" FT BINDING 442..443 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 465 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 484 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 491..493 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT BINDING 491 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0007744|PDB:2J3N" FT BINDING 622 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17512005, FT ECO:0007744|PDB:2J3N" FT NON_STD 648 FT /note="Selenocysteine" FT /evidence="ECO:0000269|PubMed:8650234" FT MOD_RES 218 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9JMH6" FT MOD_RES 281 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT DISULFID 209..214 FT /note="Redox-active" FT /evidence="ECO:0000250" FT CROSSLNK 647..648 FT /note="Cysteinyl-selenocysteine (Cys-Sec)" FT /evidence="ECO:0000250" FT VAR_SEQ 1..188 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_053819" FT VAR_SEQ 1..150 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7589432, ECO:0000303|PubMed:9774665, FT ECO:0000303|Ref.5, ECO:0000303|Ref.6, ECO:0000303|Ref.8, FT ECO:0000303|Ref.9" FT /id="VSP_031558" FT VAR_SEQ 1..139 FT /note="MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTAT FT ADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTL FT SELAAETDLPVVFVKQRKIGGHGPTLKA -> MPVDDYWLCLPASCARPFVQTVRVVQS FT CPHCCWFPGVLPSVPEPLRMPAMLPTGSHSAVLPPSHCSTAPPSTSQEPSSSADPKLCL FT SPPTSDSRQERNVQFGLA (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_031559" FT VAR_SEQ 1..106 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_031560" FT VAR_SEQ 1..98 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8999974" FT /id="VSP_031561" FT VAR_SEQ 1..51 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_031562" FT VAR_SEQ 52..100 FT /note="TADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQ -> FT MQQVMLTCKGVNRGHAVPAGPGRKPRPRRSSRLLAGEKHLTRSALLLCH (in FT isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_031563" FT VAR_SEQ 99..101 FT /note="DQT -> MSC (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8999974" FT /id="VSP_031564" FT VAR_SEQ 107..138 FT /note="LEGTLSELAAETDLPVVFVKQRKIGGHGPTLK -> MLSRLVLNSWAQAIIR FT PRPPKVLGLQVTTFSE (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_031565" FT VARIANT 365 FT /note="D -> G (in dbSNP:rs1127954)" FT /evidence="ECO:0000269|PubMed:14980707, FT ECO:0000269|PubMed:7589432" FT /id="VAR_051776" FT CONFLICT 153 FT /note="G -> S (in Ref. 4; AAQ62473)" FT /evidence="ECO:0000305" FT CONFLICT 181 FT /note="A -> P (in Ref. 6; AAF15900)" FT /evidence="ECO:0000305" FT CONFLICT 194 FT /note="V -> G (in Ref. 6; AAF15900)" FT /evidence="ECO:0000305" FT CONFLICT 200 FT /note="G -> E (in Ref. 4; AAQ62469)" FT /evidence="ECO:0000305" FT CONFLICT 202 FT /note="R -> K (in Ref. 4; AAQ62463)" FT /evidence="ECO:0000305" FT CONFLICT 215 FT /note="I -> N (in Ref. 4; AAQ62463)" FT /evidence="ECO:0000305" FT CONFLICT 297 FT /note="G -> D (in Ref. 7; BAH11490)" FT /evidence="ECO:0000305" FT CONFLICT 306 FT /note="R -> S (in Ref. 1; AAB35418/CAA62629 and 4; FT AAL15432)" FT /evidence="ECO:0000305" FT CONFLICT 365 FT /note="D -> N (in Ref. 3; AAC69621)" FT /evidence="ECO:0000305" FT CONFLICT 437 FT /note="V -> A (in Ref. 7; BAH12374)" FT /evidence="ECO:0000305" FT CONFLICT 441 FT /note="I -> M (in Ref. 7; BAH12374)" FT /evidence="ECO:0000305" FT CONFLICT 449 FT /note="K -> R (in Ref. 8; CAG38744)" FT /evidence="ECO:0000305" FT CONFLICT 641 FT /note="S -> R (in Ref. 3; AAC69621)" FT /evidence="ECO:0000305" FT STRAND 162..168 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 172..183 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 208..212 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 214..233 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 234..237 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 248..272 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 280..286 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 289..293 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 295..297 FT /evidence="ECO:0007829|PDB:2ZZ0" FT STRAND 301..309 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 313..315 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 323..326 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 330..333 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 342..346 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 350..361 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 366..372 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 374..377 FT /evidence="ECO:0007829|PDB:2ZZ0" FT HELIX 380..392 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 396..410 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 412..414 FT /evidence="ECO:0007829|PDB:2J3N" FT STRAND 416..427 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 429..439 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 443..446 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 448..450 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 453..456 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 461..463 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 479..481 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 483..485 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 486..489 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 493..508 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 522..524 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 530..534 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 537..544 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 546..548 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 549..556 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 559..562 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 563..565 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 568..570 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 571..578 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 579..582 FT /evidence="ECO:0007829|PDB:3QFA" FT STRAND 584..592 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 595..607 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 612..617 FT /evidence="ECO:0007829|PDB:3QFA" FT HELIX 625..631 FT /evidence="ECO:0007829|PDB:3QFA" FT TURN 636..639 FT /evidence="ECO:0007829|PDB:3QFA" FT MOD_RES Q16881-5:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" SQ SEQUENCE 649 AA; 70906 MW; 5A51C3F77EB03EFE CRC64; MGCAEGKAVA AAAPTELQTK GKNGDGRRRS AKDHHPGKTL PENPAGFTST ATADSRALLQ AYIDGHSVVI FSRSTCTRCT EVKKLFKSLC VPYFVLELDQ TEDGRALEGT LSELAAETDL PVVFVKQRKI GGHGPTLKAY QEGRLQKLLK MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV NVGCIPKKLM HQAALLGQAL QDSRNYGWKV EETVKHDWDR MIEAVQNHIG SLNWGYRVAL REKKVVYENA YGQFIGPHRI KATNNKGKEK IYSAERFLIA TGERPRYLGI PGDKEYCISS DDLFSLPYCP GKTLVVGASY VALECAGFLA GIGLDVTVMV RSILLRGFDQ DMANKIGEHM EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV AQSTNSEEII EGEYNTVMLA IGRDACTRKI GLETVGVKIN EKTGKIPVTD EEQTNVPYIY AIGDILEDKV ELTPVAIQAG RLLAQRLYAG STVKCDYENV PTTVFTPLEY GACGLSEEKA VEKFGEENIE VYHSYFWPLE WTIPSRDNNK CYAKIICNTK DNERVVGFHV LGPNAGEVTQ GFAAALKCGL TKKQLDSTIG IHPVCAEVFT TLSVTKRSGA SILQAGCUG //