ID THOC1_HUMAN Reviewed; 657 AA. AC Q96FV9; B2RBP6; Q15219; Q64I72; Q64I73; DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-SEP-2017, entry version 150. DE RecName: Full=THO complex subunit 1; DE Short=Tho1; DE AltName: Full=Nuclear matrix protein p84; DE Short=p84N5; DE AltName: Full=hTREX84; GN Name=THOC1; Synonyms=HPR1; 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] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP INTERACTION WITH RB1. RC TISSUE=Lymphocyte; RX PubMed=7525595; DOI=10.1083/jcb.127.3.609; RA Durfee T., Mancini M.A., Jones D., Elledge S.J., Lee W.H.; RT "The amino-terminal region of the retinoblastoma gene product binds a RT novel nuclear matrix protein that co-localizes to centers for RNA RT processing."; RL J. Cell Biol. 127:609-622(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF RP 1-86 (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP INDUCTION. RX PubMed=15358532; DOI=10.1016/j.febslet.2004.07.074; RA Gasparri F., Sola F., Locatelli G., Muzio M.; RT "The death domain protein p84N5, but not the short isoform p84N5s, is RT cell cycle-regulated and shuttles between the nucleus and the RT cytoplasm."; RL FEBS Lett. 574:13-19(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; 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 FUNCTION, PTM, DOMAIN, AND MUTAGENESIS OF LEU-617 AND TRP-620. RX PubMed=10512864; DOI=10.1091/mbc.10.10.3251; RA Doostzadeh-Cizeron J., Evans R., Yin S., Goodrich D.W.; RT "Apoptosis induced by the nuclear death domain protein p84N5 is RT inhibited by association with Rb protein."; RL Mol. Biol. Cell 10:3251-3261(1999). RN [8] RP FUNCTION. RX PubMed=10840029; DOI=10.1074/jbc.M000793200; RA Doostzadeh-Cizeron J., Yin S., Goodrich D.W.; RT "Apoptosis induced by the nuclear death domain protein p84N5 is RT associated with caspase-6 and NF-kappa B activation."; RL J. Biol. Chem. 275:25336-25341(2000). RN [9] RP FUNCTION. RX PubMed=11050087; DOI=10.1074/jbc.M006944200; RA Doostzadeh-Cizeron J., Terry N.H., Goodrich D.W.; RT "The nuclear death domain protein p84N5 activates a G2/M cell cycle RT checkpoint prior to the onset of apoptosis."; RL J. Biol. Chem. 276:1127-1132(2001). RN [10] RP FUNCTION, AND INTERACTION WITH THE TREX COMPLEX. RX PubMed=11979277; DOI=10.1038/nature746; RA Straesser K., Masuda S., Mason P., Pfannstiel J., Oppizzi M., RA Rodriguez-Navarro S., Rondon A.G., Aguilera A., Struhl K., Reed R., RA Hurt E.; RT "TREX is a conserved complex coupling transcription with messenger RNA RT export."; RL Nature 417:304-308(2002). RN [11] RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL. RX PubMed=12096345; DOI=10.1038/sj.onc.1205583; RA Evans R.L., Poe B.S., Goodrich D.W.; RT "Nuclear localization is required for induction of apoptotic cell RT death by the Rb-associated p84N5 death domain protein."; RL Oncogene 21:4691-4695(2002). RN [12] RP IDENTIFICATION IN THE TREX COMPLEX, FUNCTION OF THE TREX COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY. RX PubMed=15833825; DOI=10.1158/0008-5472.CAN-04-3624; RA Guo S., Hakimi M.A., Baillat D., Chen X., Farber M.J., RA Klein-Szanto A.J., Cooch N.S., Godwin A.K., Shiekhattar R.; RT "Linking transcriptional elongation and messenger RNA export to RT metastatic breast cancers."; RL Cancer Res. 65:3011-3016(2005). RN [13] RP IDENTIFICATION IN THE THO AND TREX COMPLEX, FUNCTION OF THE TREX RP COMPLEX, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15998806; DOI=10.1101/gad.1302205; RA Masuda S., Das R., Cheng H., Hurt E., Dorman N., Reed R.; RT "Recruitment of the human TREX complex to mRNA during splicing."; RL Genes Dev. 19:1512-1517(2005). RN [14] RP FUNCTION, AND INTERACTION WITH THOC2; DDX39B AND RNA POLYMERASE II. RX PubMed=15870275; DOI=10.1128/MCB.25.10.4023-4033.2005; RA Li Y., Wang X., Zhang X., Goodrich D.W.; RT "Human hHpr1/p84/Thoc1 regulates transcriptional elongation and RT physically links RNA polymerase II and RNA processing factors."; RL Mol. Cell. Biol. 25:4023-4033(2005). RN [15] RP FUNCTION OF THE TREX COMPLEX. RX PubMed=17190602; DOI=10.1016/j.cell.2006.10.044; RA Cheng H., Dufu K., Lee C.-S., Hsu J.L., Dias A., Reed R.; RT "Human mRNA export machinery recruited to the 5' end of mRNA."; RL Cell 127:1389-1400(2006). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [17] RP FUNCTION OF THE TREX COMPLEX. RX PubMed=18974867; DOI=10.1371/journal.ppat.1000194; RA Boyne J.R., Colgan K.J., Whitehouse A.; RT "Recruitment of the complete hTREX complex is required for Kaposi's RT sarcoma-associated herpesvirus intronless mRNA nuclear export and RT virus replication."; RL PLoS Pathog. 4:E1000194-E1000194(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-133 AND LYS-300, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-2 AND SER-560, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] 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 [22] RP FUNCTION. RX PubMed=22144908; DOI=10.1371/journal.pgen.1002386; RA Dominguez-Sanchez M.S., Barroso S., Gomez-Gonzalez B., Luna R., RA Aguilera A.; RT "Genome instability and transcription elongation impairment in human RT cells depleted of THO/TREX."; RL PLoS Genet. 7:E1002386-E1002386(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-4; SER-537; RP THR-542 AND SER-560, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP FUNCTION. RX PubMed=23222130; DOI=10.1093/nar/gks1188; RA Chi B., Wang Q., Wu G., Tan M., Wang L., Shi M., Chang X., Cheng H.; RT "Aly and THO are required for assembly of the human TREX complex and RT association of TREX components with the spliced mRNA."; RL Nucleic Acids Res. 41:1294-1306(2013). RN [25] RP UBIQUITINATION BY NEDD4. RX PubMed=23460917; DOI=10.1371/journal.pone.0057995; RA Song F., Fan C., Wang X., Goodrich D.W.; RT "The Thoc1 encoded ribonucleoprotein is a substrate for the NEDD4-1 E3 RT ubiquitin protein ligase."; RL PLoS ONE 8:E57995-E57995(2013). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-31; LYS-408 AND LYS-595, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [27] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-595, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [28] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-31, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [29] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-595, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.O114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to RT replication stress reveals novel small ubiquitin-like modified target RT proteins and acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [30] RP INTERACTION WITH LUZP4. RX PubMed=25662211; DOI=10.1093/nar/gkv070; RA Viphakone N., Cumberbatch M.G., Livingstone M.J., Heath P.R., RA Dickman M.J., Catto J.W., Wilson S.A.; RT "Luzp4 defines a new mRNA export pathway in cancer cells."; RL Nucleic Acids Res. 43:2353-2366(2015). RN [31] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-31; LYS-580 AND LYS-595, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co- RT modification with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [32] RP STRUCTURE BY NMR OF 561-657. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the death domain of nuclear matrix protein RT p84."; RL Submitted (JUL-2005) to the PDB data bank. CC -!- FUNCTION: Required for efficient export of polyadenylated RNA. CC Acts as component of the THO subcomplex of the TREX complex which CC is thought to couple mRNA transcription, processing and nuclear CC export, and which specifically associates with spliced mRNA and CC not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by CC a transcription-independent mechanism, binds to mRNA upstream of CC the exon-junction complex (EJC) and is recruited in a CC splicing- and cap-dependent manner to a region near the 5' end of CC the mRNA where it functions in mRNA export to the cytoplasm via CC the TAP/NFX1 pathway. The TREX complex is essential for the export CC of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs CC and infectious virus production. Regulates transcriptional CC elongation of a subset of genes. Involved in genome stability by CC preventing co-transcriptional R-loop formation. CC -!- FUNCTION: Participates in an apoptotic pathway which is CC characterized by activation of caspase-6, increases in the CC expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This CC pathway does not require p53/TP53, nor does the presence of CC p53/TP53 affect the efficiency of cell killing. Activates a G2/M CC cell cycle checkpoint prior to the onset of apoptosis. Apoptosis CC is inhibited by association with RB1. CC -!- SUBUNIT: Component of the THO complex, which is composed of THOC1, CC THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least CC ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the CC transcription/export (TREX) complex which seems to have a dynamic CC structure involving ATP-dependent remodeling. Binds to the CC hypophosphorylated form of RB1. Interacts with THOC2, DDX39B and CC RNA polymerase II. Interacts with THOC5 (By similarity). Interacts CC with LUZP4. {ECO:0000250|UniProtKB:Q8R3N6, CC ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:15833825, CC ECO:0000269|PubMed:15870275, ECO:0000269|PubMed:15998806, CC ECO:0000269|PubMed:25662211, ECO:0000269|PubMed:7525595}. CC -!- INTERACTION: CC Q96BY2:MOAP1; NbExp=5; IntAct=EBI-1765605, EBI-739825; CC Q9UJ41:RABGEF1; NbExp=3; IntAct=EBI-1765605, EBI-913954; CC Q04864-2:REL; NbExp=4; IntAct=EBI-1765605, EBI-10829018; CC Q13769:THOC5; NbExp=9; IntAct=EBI-1765605, EBI-5280316; CC Q9BYV2:TRIM54; NbExp=3; IntAct=EBI-1765605, EBI-2130429; CC Q8N6Y0:USHBP1; NbExp=3; IntAct=EBI-1765605, EBI-739895; CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus speckle. Nucleus, CC nucleoplasm. Nucleus matrix. Cytoplasm. Note=Can shuttle between CC the nucleus and cytoplasm. Nuclear localization is required for CC induction of apoptotic cell death. Translocates to the cytoplasm CC during the early phase of apoptosis execution. CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96FV9-1; Sequence=Displayed; CC Name=2; Synonyms=p84N5s; CC IsoId=Q96FV9-2; Sequence=VSP_038073, VSP_038074; CC Note=May be due to an intron retention.; CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in various cancer cell CC lines. Expressed at very low levels in normal breast epithelial CC cells and highly expressed in breast tumors. Expression is CC strongly associated with an aggressive phenotype of breast tumors CC and expression correlates with tumor size and the metastatic state CC of the tumor progression. {ECO:0000269|PubMed:15358532, CC ECO:0000269|PubMed:15833825}. CC -!- INDUCTION: Up-regulated during cell proliferation. CC {ECO:0000269|PubMed:15358532}. CC -!- DOMAIN: An intact death domain is needed for apoptosis. CC {ECO:0000269|PubMed:10512864}. CC -!- PTM: Expression is altered specifically during apoptosis and is CC accompanied by the appearance of novel forms with smaller apparent CC molecular mass. CC -!- PTM: Polyubiquitinated, leading to proteasomal degradation; CC probably involves NEDD4. {ECO:0000269|PubMed:23460917}. 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; L36529; AAA53571.1; -; mRNA. DR EMBL; AY573302; AAT81408.1; -; mRNA. DR EMBL; AY573303; AAT81409.1; -; mRNA. DR EMBL; AK314755; BAG37293.1; -; mRNA. DR EMBL; AP000845; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471113; EAX01732.1; -; Genomic_DNA. DR EMBL; BC010381; AAH10381.1; -; mRNA. DR CCDS; CCDS45820.1; -. [Q96FV9-1] DR PIR; A53545; A53545. DR RefSeq; NP_005122.2; NM_005131.2. [Q96FV9-1] DR UniGene; Hs.712543; -. DR PDB; 1WXP; NMR; -; A=561-657. DR PDBsum; 1WXP; -. DR ProteinModelPortal; Q96FV9; -. DR SMR; Q96FV9; -. DR BioGrid; 115305; 88. DR CORUM; Q96FV9; -. DR IntAct; Q96FV9; 79. DR MINT; MINT-4536762; -. DR STRING; 9606.ENSP00000261600; -. DR iPTMnet; Q96FV9; -. DR PhosphoSitePlus; Q96FV9; -. DR BioMuta; THOC1; -. DR DMDM; 37999906; -. DR EPD; Q96FV9; -. DR MaxQB; Q96FV9; -. DR PaxDb; Q96FV9; -. DR PeptideAtlas; Q96FV9; -. DR PRIDE; Q96FV9; -. DR DNASU; 9984; -. DR Ensembl; ENST00000261600; ENSP00000261600; ENSG00000079134. [Q96FV9-1] DR GeneID; 9984; -. DR KEGG; hsa:9984; -. DR UCSC; uc002kkj.5; human. [Q96FV9-1] DR CTD; 9984; -. DR DisGeNET; 9984; -. DR EuPathDB; HostDB:ENSG00000079134.11; -. DR GeneCards; THOC1; -. DR HGNC; HGNC:19070; THOC1. DR HPA; HPA019096; -. DR HPA; HPA019687; -. DR MIM; 606930; gene. DR neXtProt; NX_Q96FV9; -. DR OpenTargets; ENSG00000079134; -. DR PharmGKB; PA134887435; -. DR eggNOG; KOG2491; Eukaryota. DR eggNOG; ENOG410XQEX; LUCA. DR GeneTree; ENSGT00390000016232; -. DR HOGENOM; HOG000008123; -. DR HOVERGEN; HBG060294; -. DR InParanoid; Q96FV9; -. DR KO; K12878; -. DR OMA; VSEFNLD; -. DR PhylomeDB; Q96FV9; -. DR TreeFam; TF314796; -. DR Reactome; R-HSA-109688; Cleavage of Growing Transcript in the Termination Region. DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript. DR Reactome; R-HSA-72187; mRNA 3'-end processing. DR ChiTaRS; THOC1; human. DR EvolutionaryTrace; Q96FV9; -. DR GeneWiki; THOC1; -. DR GenomeRNAi; 9984; -. DR PRO; PR:Q96FV9; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; ENSG00000079134; -. DR CleanEx; HS_THOC1; -. DR ExpressionAtlas; Q96FV9; baseline and differential. DR Genevisible; Q96FV9; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000347; C:THO complex; IDA:UniProtKB. DR GO; GO:0000445; C:THO complex part of transcription export complex; IDA:UniProtKB. DR GO; GO:0000346; C:transcription export complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome. DR GO; GO:0006406; P:mRNA export from nucleus; IDA:UniProtKB. DR GO; GO:2000002; P:negative regulation of DNA damage checkpoint; IMP:UniProtKB. DR GO; GO:0048297; P:negative regulation of isotype switching to IgA isotypes; ISS:UniProtKB. DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; IMP:UniProtKB. DR GO; GO:0000018; P:regulation of DNA recombination; IMP:UniProtKB. DR GO; GO:0032784; P:regulation of DNA-templated transcription, elongation; IDA:UniProtKB. DR GO; GO:0031297; P:replication fork processing; IMP:UniProtKB. DR GO; GO:0006405; P:RNA export from nucleus; TAS:Reactome. DR GO; GO:0006396; P:RNA processing; TAS:ProtInc. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome. DR GO; GO:0046784; P:viral mRNA export from host cell nucleus; IDA:UniProtKB. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR021861; THO_THOC1. DR Pfam; PF00531; Death; 1. DR Pfam; PF11957; efThoc1; 1. DR SMART; SM00005; DEATH; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50017; DEATH_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Complete proteome; Cytoplasm; DNA-binding; Isopeptide bond; KW mRNA processing; mRNA splicing; mRNA transport; Nucleus; KW Phosphoprotein; Reference proteome; RNA-binding; Transcription; KW Transcription regulation; Transport; Ubl conjugation. FT CHAIN 1 657 THO complex subunit 1. FT /FTId=PRO_0000072520. FT DOMAIN 570 653 Death. {ECO:0000255|PROSITE- FT ProRule:PRU00064}. FT MOTIF 414 430 Nuclear localization signal. FT {ECO:0000269|PubMed:12096345}. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 2 2 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 4 4 Phosphothreonine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 133 133 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 300 300 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 537 537 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 542 542 Phosphothreonine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 560 560 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163}. FT CROSSLNK 31 31 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447, FT ECO:0000244|PubMed:25772364, FT ECO:0000244|PubMed:28112733}. FT CROSSLNK 408 408 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 580 580 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:28112733}. FT CROSSLNK 595 595 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT {ECO:0000244|PubMed:25114211}. FT CROSSLNK 595 595 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25114211, FT ECO:0000244|PubMed:25218447, FT ECO:0000244|PubMed:25755297, FT ECO:0000244|PubMed:28112733}. FT VAR_SEQ 363 377 LLSENPPDGERFSKM -> VSSTRNKPMIEKMEI (in FT isoform 2). FT {ECO:0000303|PubMed:15358532}. FT /FTId=VSP_038073. FT VAR_SEQ 378 657 Missing (in isoform 2). FT {ECO:0000303|PubMed:15358532}. FT /FTId=VSP_038074. FT MUTAGEN 617 617 L->P: Loss of ability to induce FT apoptosis. Interferes with normal FT response of SaOS-2 cells to radiation. FT {ECO:0000269|PubMed:10512864}. FT MUTAGEN 620 620 W->P,R: Loss of ability to induce FT apoptosis. Interferes with normal FT response of SaOS-2 cells to radiation. FT {ECO:0000269|PubMed:10512864}. FT CONFLICT 71 71 N -> H (in Ref. 2; AAT81408). FT {ECO:0000305}. FT CONFLICT 86 86 G -> A (in Ref. 2; AAT81408). FT {ECO:0000305}. FT CONFLICT 130 130 S -> A (in Ref. 1; AAA53571). FT {ECO:0000305}. FT CONFLICT 134 134 N -> S (in Ref. 3; BAG37293). FT {ECO:0000305}. FT CONFLICT 433 433 M -> T (in Ref. 1; AAA53571). FT {ECO:0000305}. FT CONFLICT 480 480 V -> A (in Ref. 1; AAA53571). FT {ECO:0000305}. FT CONFLICT 487 487 V -> M (in Ref. 1; AAA53571). FT {ECO:0000305}. FT CONFLICT 498 498 R -> K (in Ref. 1; AAA53571). FT {ECO:0000305}. FT CONFLICT 519 519 P -> Q (in Ref. 1; AAA53571). FT {ECO:0000305}. FT STRAND 565 567 {ECO:0000244|PDB:1WXP}. FT HELIX 571 581 {ECO:0000244|PDB:1WXP}. FT TURN 582 584 {ECO:0000244|PDB:1WXP}. FT HELIX 585 588 {ECO:0000244|PDB:1WXP}. FT TURN 589 593 {ECO:0000244|PDB:1WXP}. FT HELIX 596 605 {ECO:0000244|PDB:1WXP}. FT HELIX 609 624 {ECO:0000244|PDB:1WXP}. FT HELIX 625 627 {ECO:0000244|PDB:1WXP}. FT HELIX 630 639 {ECO:0000244|PDB:1WXP}. FT HELIX 643 650 {ECO:0000244|PDB:1WXP}. SQ SEQUENCE 657 AA; 75666 MW; DB7980BD0F252DAB CRC64; MSPTPPLFSL PEARTRFTKS TREALNNKNI KPLLSTFSQV PGSENEKKCT LDQAFRGILE EEIINHSSCE NVLAIISLAI GGVTEGICTA STPFVLLGDV LDCLPLDQCD TIFTFVEKNV ATWKSNTFYS AGKNYLLRMC NDLLRRLSKS QNTVFCGRIQ LFLARLFPLS EKSGLNLQSQ FNLENVTVFN TNEQESTLGQ KHTEDREEGM DVEEGEMGDE EAPTTCSIPI DYNLYRKFWS LQDYFRNPVQ CYEKISWKTF LKYSEEVLAV FKSYKLDDTQ ASRKKMEELK TGGEHVYFAK FLTSEKLMDL QLSDSNFRRH ILLQYLILFQ YLKGQVKFKS SNYVLTDEQS LWIEDTTKSV YQLLSENPPD GERFSKMVEH ILNTEENWNS WKNEGCPSFV KERTSDTKPT RIIRKRTAPE DFLGKGPTKK ILMGNEELTR LWNLCPDNME ACKSETREHM PTLEEFFEEA IEQADPENMV ENEYKAVNNS NYGWRALRLL ARRSPHFFQP TNQQFKSLPE YLENMVIKLA KELPPPSEEI KTGEDEDEED NDALLKENES PDVRRDKPVT GEQIEVFANK LGEQWKILAP YLEMKDSEIR QIECDSEDMK MRAKQLLVAW QDQEGVHATP ENLINALNKS GLSDLAESLT NDNETNS //