ID   THOC1_MOUSE             Reviewed;         657 AA.
AC   Q8R3N6; Q8BWD5; Q8BXY3;
DT   10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=THO complex subunit 1;
DE            Short=Tho1;
DE   AltName: Full=Nuclear matrix protein p84;
GN   Name=Thoc1; Synonyms=Hpr1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cerebellum, Head, and Olfactory bulb;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II; TISSUE=Mammary tumor;
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   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP   STAGE.
RX   PubMed=16705185; DOI=10.1128/mcb.02163-05;
RA   Wang X., Chang Y., Li Y., Zhang X., Goodrich D.W.;
RT   "Thoc1/Hpr1/p84 is essential for early embryonic development in the
RT   mouse.";
RL   Mol. Cell. Biol. 26:4362-4367(2006).
RN   [4]
RP   INTERACTION WITH THOC5.
RX   PubMed=16909111; DOI=10.1038/sj.onc.1209853;
RA   Mancini A., El Bounkari O., Norrenbrock A.-F., Scherr M., Schaefer D.,
RA   Eder M., Banham A.H., Pulford K., Lyne L., Whetton A.D., Tamura T.;
RT   "FMIP controls the adipocyte lineage commitment of C2C12 cells by
RT   downmodulation of C/EBP alpha.";
RL   Oncogene 26:1020-1027(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19307311; DOI=10.1128/mcb.01633-08;
RA   Wang X., Chinnam M., Wang J., Wang Y., Zhang X., Marcon E., Moens P.,
RA   Goodrich D.W.;
RT   "Thoc1 deficiency compromises gene expression necessary for normal testis
RT   development in the mouse.";
RL   Mol. Cell. Biol. 29:2794-2803(2009).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Liver, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [8]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=32776944; DOI=10.1371/journal.pgen.1008953;
RA   Zhang L., Gao Y., Zhang R., Sun F., Cheng C., Qian F., Duan X., Wei G.,
RA   Sun C., Pang X., Chen P., Chai R., Yang T., Wu H., Liu D.;
RT   "THOC1 deficiency leads to late-onset nonsyndromic hearing loss through
RT   p53-mediated hair cell apoptosis.";
RL   PLoS Genet. 16:e1008953-e1008953(2020).
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. Regulates transcriptional
CC       elongation of a subset of genes. Involved in genome stability by
CC       preventing co-transcriptional R-loop formation (By similarity). May
CC       play a role in hair cell formation, hence may be involved in hearing
CC       (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q7SYB2}.
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 (By
CC       similarity). Essential for early embryonic development. Required for
CC       normal gene expression during postnatal testis development.
CC       {ECO:0000250, ECO:0000269|PubMed:16705185,
CC       ECO:0000269|PubMed:19307311}.
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 (By similarity). Interacts with THOC5 (PubMed:16909111).
CC       Interacts with LUZP4 (By similarity). {ECO:0000250|UniProtKB:Q96FV9,
CC       ECO:0000269|PubMed:16909111}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32776944}. Nucleus,
CC       nucleoplasm {ECO:0000269|PubMed:16705185}. Nucleus matrix
CC       {ECO:0000250}. Cytoplasm, cytosol {ECO:0000269|PubMed:32776944}.
CC       Note=Predominantly localized in the nucleus (PubMed:32776944). Shuttles
CC       between the nucleus and cytosol. Nuclear localization is required for
CC       induction of apoptotic cell death. Translocates to the cytoplasm during
CC       the early phase of apoptosis execution (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:32776944}.
CC   -!- TISSUE SPECIFICITY: In the inner ear, specifically expressed in inner
CC       and outer hair cells (at protein level). {ECO:0000269|PubMed:32776944}.
CC   -!- DEVELOPMENTAL STAGE: Widely expressed during embryonic development.
CC       {ECO:0000269|PubMed:16705185}.
CC   -!- DOMAIN: An intact death domain is needed for apoptosis.
CC       {ECO:0000250|UniProtKB:Q96FV9}.
CC   -!- PTM: Expression is altered specifically during apoptosis and is
CC       accompanied by the appearance of novel forms with smaller apparent
CC       molecular mass. {ECO:0000250}.
CC   -!- PTM: Polyubiquitinated, leading to proteasomal degradation; probably
CC       involves NEDD4. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Mice show early embryonic lethality and severely
CC       diminished fertility. {ECO:0000269|PubMed:16705185,
CC       ECO:0000269|PubMed:19307311}.
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DR   EMBL; AK031785; BAC27548.1; -; mRNA.
DR   EMBL; AK032200; BAC27754.1; -; mRNA.
DR   EMBL; AK042867; BAC31387.2; -; mRNA.
DR   EMBL; BC024951; AAH24951.1; -; mRNA.
DR   CCDS; CCDS37733.1; -.
DR   RefSeq; NP_705780.1; NM_153552.3.
DR   AlphaFoldDB; Q8R3N6; -.
DR   SMR; Q8R3N6; -.
DR   BioGRID; 230364; 20.
DR   IntAct; Q8R3N6; 2.
DR   STRING; 10090.ENSMUSP00000025137; -.
DR   iPTMnet; Q8R3N6; -.
DR   PhosphoSitePlus; Q8R3N6; -.
DR   SwissPalm; Q8R3N6; -.
DR   EPD; Q8R3N6; -.
DR   jPOST; Q8R3N6; -.
DR   MaxQB; Q8R3N6; -.
DR   PaxDb; 10090-ENSMUSP00000025137; -.
DR   PeptideAtlas; Q8R3N6; -.
DR   ProteomicsDB; 262817; -.
DR   Pumba; Q8R3N6; -.
DR   Antibodypedia; 4748; 395 antibodies from 32 providers.
DR   DNASU; 225160; -.
DR   Ensembl; ENSMUST00000025137.9; ENSMUSP00000025137.8; ENSMUSG00000024287.9.
DR   GeneID; 225160; -.
DR   KEGG; mmu:225160; -.
DR   UCSC; uc008eal.1; mouse.
DR   AGR; MGI:1919668; -.
DR   CTD; 9984; -.
DR   MGI; MGI:1919668; Thoc1.
DR   VEuPathDB; HostDB:ENSMUSG00000024287; -.
DR   eggNOG; KOG2491; Eukaryota.
DR   GeneTree; ENSGT00390000016232; -.
DR   HOGENOM; CLU_027906_0_0_1; -.
DR   InParanoid; Q8R3N6; -.
DR   OMA; LWNSWKN; -.
DR   OrthoDB; 5490969at2759; -.
DR   PhylomeDB; Q8R3N6; -.
DR   TreeFam; TF314796; -.
DR   Reactome; R-MMU-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR   Reactome; R-MMU-72187; mRNA 3'-end processing.
DR   Reactome; R-MMU-73856; RNA Polymerase II Transcription Termination.
DR   BioGRID-ORCS; 225160; 28 hits in 115 CRISPR screens.
DR   ChiTaRS; Thoc1; mouse.
DR   PRO; PR:Q8R3N6; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q8R3N6; Protein.
DR   Bgee; ENSMUSG00000024287; Expressed in cumulus cell and 258 other cell types or tissues.
DR   ExpressionAtlas; Q8R3N6; baseline and differential.
DR   GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0000347; C:THO complex; ISO:MGI.
DR   GO; GO:0000445; C:THO complex part of transcription export complex; ISO:MGI.
DR   GO; GO:0000346; C:transcription export complex; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0006406; P:mRNA export from nucleus; ISS:UniProtKB.
DR   GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR   GO; GO:2000002; P:negative regulation of DNA damage checkpoint; ISO:MGI.
DR   GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; ISO:MGI.
DR   GO; GO:0000018; P:regulation of DNA recombination; ISO:MGI.
DR   GO; GO:0032784; P:regulation of DNA-templated transcription elongation; ISO:MGI.
DR   GO; GO:0031297; P:replication fork processing; ISO:MGI.
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; ISO:MGI.
DR   CDD; cd08318; Death_NMPP84; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR000488; Death_domain.
DR   InterPro; IPR021861; THO_THOC1.
DR   PANTHER; PTHR13265; THO COMPLEX SUBUNIT 1; 1.
DR   PANTHER; PTHR13265:SF2; THO COMPLEX SUBUNIT 1; 1.
DR   Pfam; PF00531; Death; 1.
DR   Pfam; PF11957; efThoc1; 1.
DR   SMART; SM00005; DEATH; 1.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   PROSITE; PS50017; DEATH_DOMAIN; 1.
DR   Genevisible; Q8R3N6; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Apoptosis; Cytoplasm; DNA-binding; Isopeptide bond;
KW   mRNA processing; mRNA splicing; mRNA transport; Nucleus; Phosphoprotein;
KW   Reference proteome; RNA-binding; Transcription; Transcription regulation;
KW   Transport; Ubl conjugation.
FT   CHAIN           1..657
FT                   /note="THO complex subunit 1"
FT                   /id="PRO_0000072521"
FT   DOMAIN          570..653
FT                   /note="Death"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT   REGION          194..221
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:0000250|UniProtKB:Q96FV9"
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:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         4
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         133
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         300
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         537
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         542
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   MOD_RES         560
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   CROSSLNK        31
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   CROSSLNK        408
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   CROSSLNK        580
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   CROSSLNK        595
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
FT   CROSSLNK        595
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FV9"
SQ   SEQUENCE   657 AA;  75436 MW;  E4235E395B5A82BC CRC64;
     MSPTPALFSL PEARTRFTKS TREALNNKNI KPLLTAFSQL PGSENEKKCT LDQAFRGVLE
     EEIINHSACE NVLAIISLAI GGVTESVCTA STPFVLLGDV LDCLPLDQCD TIFTFVEKNV
     ATWKSNTFYS AGKNYLLRMC NDLLRRLSKS QNTVFCGRIQ LFLARLFPLS EKSGLNLQSQ
     FNLENVTVFN TNEQESTLGQ KHTEDREEGM DVEEGEMGDD EAPTTCSIPI DYNLYRKFWS
     LQDYFRNPVQ CYEKISWKTF LKYSEEVLAV FKSYKLDDTQ ASRKKMEELK TGGEHVYFAK
     FLTSEKLMDL QLSDSNFRRH ILLQYLILFQ YLKGQVKFKS SNYVLTDEQS LWIEDTTKSV
     YQLLSENPPD GERFSKMVEH ILNTEENWNS WKNEGCPSFV KERASDTKPT RVVRKRAAPE
     DFLGKGPNKK ILIGNEELTR LWNLCPDNME ACKSETREYM PTLEEFFEEA IEQADPENMV
     ESEYKAVNNS NYGWRALRLL ARRSPHFFQP TNQQFKSLPE YLENMVIKLA KELPPPSEEI
     KTGEDEDEED NDALLKENES PDVRRDKPIT GEQIESFANK LGEQWKILAP YLEIKDSDIR
     QIECDSEDMK MRAKQLLVAW QDQEGVHATT DNLISALNKS GLSDLAESLT NDTETNS
//