THOC1_HUMAN
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 03-AUG-2022, entry version 181.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 novel
RT nuclear matrix protein that co-localizes to centers for RNA processing.";
RL J. Cell Biol. 127:609-622(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 1-86
RP (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND 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 cell
RT cycle-regulated and shuttles between the nucleus and the 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., 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 [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., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., 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., 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 (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 project:
RT 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 inhibited
RT 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 associated
RT 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 death by
RT 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., Klein-Szanto A.J.,
RA Cooch N.S., Godwin A.K., Shiekhattar R.;
RT "Linking transcriptional elongation and messenger RNA export to metastatic
RT breast cancers.";
RL Cancer Res. 65:3011-3016(2005).
RN [13]
RP IDENTIFICATION IN THE THO AND TREX COMPLEX, FUNCTION OF THE TREX COMPLEX,
RP 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 physically
RT 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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT 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 virus
RT replication.";
RL PLoS Pathog. 4:E1000194-E1000194(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP 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., Walther T.C.,
RA 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 SCALE
RP ANALYSIS] AT SER-2 AND SER-560, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., 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 [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 cells
RT 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; THR-542
RP AND SER-560, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 MASS
RP 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 MASS
RP 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 MASS
RP 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 replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT 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., Dickman M.J.,
RA 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-modification
RT 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 p84.";
RL Submitted (JUL-2005) to the PDB data bank.
CC -!- FUNCTION: Required for efficient export of polyadenylated RNA. Acts as
CC component of the THO subcomplex of the TREX complex which is thought to
CC couple mRNA transcription, processing and nuclear export, and which
CC specifically associates with spliced mRNA and not with unspliced pre-
CC mRNA. TREX is recruited to spliced mRNAs by a transcription-independent
CC mechanism, binds to mRNA upstream of the exon-junction complex (EJC)
CC and is recruited in a splicing- and cap-dependent manner to a region
CC near the 5' end of the mRNA where it functions in mRNA export to the
CC cytoplasm via the TAP/NFX1 pathway. The TREX complex is essential for
CC the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless
CC mRNAs 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 characterized
CC by activation of caspase-6, increases in the expression of BAK1 and
CC BCL2L1 and activation of NF-kappa-B. This pathway does not require
CC p53/TP53, nor does the presence of p53/TP53 affect the efficiency of
CC cell killing. Activates a G2/M cell cycle checkpoint prior to the onset
CC of apoptosis. Apoptosis 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 RNA
CC polymerase II. Interacts with THOC5 (By similarity). Interacts with
CC LUZP4. {ECO:0000250|UniProtKB:Q8R3N6, ECO:0000269|PubMed:11979277,
CC ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15870275,
CC ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:25662211,
CC ECO:0000269|PubMed:7525595}.
CC -!- INTERACTION:
CC Q96FV9; O95994: AGR2; NbExp=3; IntAct=EBI-1765605, EBI-712648;
CC Q96FV9; Q6PJH3: AKAP9; NbExp=3; IntAct=EBI-1765605, EBI-11745576;
CC Q96FV9; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-1765605, EBI-11519926;
CC Q96FV9; P78358: CTAG1B; NbExp=3; IntAct=EBI-1765605, EBI-1188472;
CC Q96FV9; O00471: EXOC5; NbExp=3; IntAct=EBI-1765605, EBI-949824;
CC Q96FV9; O15481: MAGEB4; NbExp=3; IntAct=EBI-1765605, EBI-751857;
CC Q96FV9; Q96BY2: MOAP1; NbExp=7; IntAct=EBI-1765605, EBI-739825;
CC Q96FV9; P26367: PAX6; NbExp=3; IntAct=EBI-1765605, EBI-747278;
CC Q96FV9; Q9BZL4: PPP1R12C; NbExp=3; IntAct=EBI-1765605, EBI-721802;
CC Q96FV9; Q9UJ41: RABGEF1; NbExp=3; IntAct=EBI-1765605, EBI-913954;
CC Q96FV9; Q04864-2: REL; NbExp=3; IntAct=EBI-1765605, EBI-10829018;
CC Q96FV9; O75478: TADA2A; NbExp=3; IntAct=EBI-1765605, EBI-742268;
CC Q96FV9; Q13769: THOC5; NbExp=10; IntAct=EBI-1765605, EBI-5280316;
CC Q96FV9; P14373: TRIM27; NbExp=3; IntAct=EBI-1765605, EBI-719493;
CC Q96FV9; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-1765605, EBI-2130429;
CC Q96FV9; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-1765605, EBI-739895;
CC Q96FV9; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-1765605, EBI-12030590;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus speckle. Nucleus,
CC nucleoplasm. Nucleus matrix. Cytoplasm. Note=Can shuttle between the
CC nucleus and cytoplasm. Nuclear localization is required for induction
CC of apoptotic cell death. Translocates to the cytoplasm during the early
CC 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 -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in various cancer cell lines.
CC Expressed at very low levels in normal breast epithelial cells and
CC highly expressed in breast tumors. Expression is strongly associated
CC with an aggressive phenotype of breast tumors and expression correlates
CC with tumor size and the metastatic state of the tumor progression.
CC {ECO:0000269|PubMed:15358532, 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; probably
CC involves NEDD4. {ECO:0000269|PubMed:23460917}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
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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 PDB; 1WXP; NMR; -; A=561-657.
DR PDB; 7APK; EM; 3.30 A; A/I/a/i=2-657.
DR PDBsum; 1WXP; -.
DR PDBsum; 7APK; -.
DR AlphaFoldDB; Q96FV9; -.
DR SMR; Q96FV9; -.
DR BioGRID; 115305; 166.
DR CORUM; Q96FV9; -.
DR IntAct; Q96FV9; 91.
DR MINT; Q96FV9; -.
DR STRING; 9606.ENSP00000261600; -.
DR GlyGen; Q96FV9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96FV9; -.
DR MetOSite; Q96FV9; -.
DR PhosphoSitePlus; Q96FV9; -.
DR BioMuta; THOC1; -.
DR DMDM; 37999906; -.
DR EPD; Q96FV9; -.
DR jPOST; Q96FV9; -.
DR MassIVE; Q96FV9; -.
DR MaxQB; Q96FV9; -.
DR PaxDb; Q96FV9; -.
DR PeptideAtlas; Q96FV9; -.
DR PRIDE; Q96FV9; -.
DR ProteomicsDB; 76564; -. [Q96FV9-1]
DR ProteomicsDB; 76565; -. [Q96FV9-2]
DR Antibodypedia; 4748; 356 antibodies from 32 providers.
DR DNASU; 9984; -.
DR Ensembl; ENST00000261600.11; ENSP00000261600.6; ENSG00000079134.13. [Q96FV9-1]
DR GeneID; 9984; -.
DR KEGG; hsa:9984; -.
DR MANE-Select; ENST00000261600.11; ENSP00000261600.6; NM_005131.3; NP_005122.2.
DR UCSC; uc002kkj.5; human. [Q96FV9-1]
DR CTD; 9984; -.
DR DisGeNET; 9984; -.
DR GeneCards; THOC1; -.
DR HGNC; HGNC:19070; THOC1.
DR HPA; ENSG00000079134; Low tissue specificity.
DR MIM; 606930; gene.
DR neXtProt; NX_Q96FV9; -.
DR OpenTargets; ENSG00000079134; -.
DR PharmGKB; PA134887435; -.
DR VEuPathDB; HostDB:ENSG00000079134; -.
DR eggNOG; KOG2491; Eukaryota.
DR GeneTree; ENSGT00390000016232; -.
DR HOGENOM; CLU_027906_0_0_1; -.
DR InParanoid; Q96FV9; -.
DR OrthoDB; 403879at2759; -.
DR PhylomeDB; Q96FV9; -.
DR TreeFam; TF314796; -.
DR PathwayCommons; Q96FV9; -.
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 Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR SignaLink; Q96FV9; -.
DR SIGNOR; Q96FV9; -.
DR BioGRID-ORCS; 9984; 677 hits in 1093 CRISPR screens.
DR ChiTaRS; THOC1; human.
DR EvolutionaryTrace; Q96FV9; -.
DR GeneWiki; THOC1; -.
DR GenomeRNAi; 9984; -.
DR Pharos; Q96FV9; Tbio.
DR PRO; PR:Q96FV9; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q96FV9; protein.
DR Bgee; ENSG00000079134; Expressed in calcaneal tendon and 203 other tissues.
DR ExpressionAtlas; Q96FV9; baseline and differential.
DR Genevisible; Q96FV9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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:0006406; P:mRNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
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: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:0046784; P:viral mRNA export from host cell nucleus; IDA:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR021861; THO_THOC1.
DR PANTHER; PTHR13265; PTHR13265; 1.
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; Cytoplasm;
KW DNA-binding; Isopeptide bond; mRNA processing; mRNA splicing;
KW mRNA transport; Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW Transcription; Transcription regulation; Transport; Ubl conjugation.
FT CHAIN 1..657
FT /note="THO complex subunit 1"
FT /id="PRO_0000072520"
FT DOMAIN 570..653
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 194..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 533..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 414..430
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:12096345"
FT COMPBIAS 541..555
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 4
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 133
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 300
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 537
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 542
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 31
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 408
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 580
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 595
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 595
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 363..377
FT /note="LLSENPPDGERFSKM -> VSSTRNKPMIEKMEI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15358532"
FT /id="VSP_038073"
FT VAR_SEQ 378..657
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15358532"
FT /id="VSP_038074"
FT MUTAGEN 617
FT /note="L->P: Loss of ability to induce apoptosis.
FT Interferes with normal response of SaOS-2 cells to
FT radiation."
FT /evidence="ECO:0000269|PubMed:10512864"
FT MUTAGEN 620
FT /note="W->P,R: Loss of ability to induce apoptosis.
FT Interferes with normal response of SaOS-2 cells to
FT radiation."
FT /evidence="ECO:0000269|PubMed:10512864"
FT CONFLICT 71
FT /note="N -> H (in Ref. 2; AAT81408)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="G -> A (in Ref. 2; AAT81408)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="S -> A (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="N -> S (in Ref. 3; BAG37293)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="M -> T (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="V -> A (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="V -> M (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="R -> K (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="P -> Q (in Ref. 1; AAA53571)"
FT /evidence="ECO:0000305"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 30..36
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 46..64
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 72..83
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 134..146
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 153..166
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 232..246
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 249..252
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 255..274
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 315..333
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 347..365
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 368..370
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 371..391
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 565..567
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 571..581
FT /evidence="ECO:0007829|PDB:1WXP"
FT TURN 582..584
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 585..588
FT /evidence="ECO:0007829|PDB:1WXP"
FT TURN 589..593
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 596..605
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 609..624
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 625..627
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 630..639
FT /evidence="ECO:0007829|PDB:1WXP"
FT HELIX 643..650
FT /evidence="ECO:0007829|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
