THOC1_MOUSE
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 03-AUG-2022, entry version 159.
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).
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).
CC {ECO:0000250}.
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 speckle {ECO:0000250}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:16705185}. Nucleus matrix
CC {ECO:0000250}. Cytoplasm {ECO:0000250}. 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 (By similarity). {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed during embryonic development.
CC {ECO:0000269|PubMed:16705185}.
CC -!- DOMAIN: An intact death domain is needed for apoptosis. {ECO:0000250}.
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; Q8R3N6; -.
DR PeptideAtlas; Q8R3N6; -.
DR PRIDE; Q8R3N6; -.
DR ProteomicsDB; 262817; -.
DR Antibodypedia; 4748; 356 antibodies from 32 providers.
DR DNASU; 225160; -.
DR Ensembl; ENSMUST00000025137; ENSMUSP00000025137; ENSMUSG00000024287.
DR GeneID; 225160; -.
DR KEGG; mmu:225160; -.
DR UCSC; uc008eal.1; mouse.
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; EEMWNNW; -.
DR OrthoDB; 403879at2759; -.
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; 27 hits in 111 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 256 other tissues.
DR ExpressionAtlas; Q8R3N6; baseline and differential.
DR Genevisible; Q8R3N6; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0048297; P:negative regulation of isotype switching to IgA isotypes; IMP:UniProtKB.
DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; ISS:UniProtKB.
DR GO; GO:0000018; P:regulation of DNA recombination; ISS:UniProtKB.
DR GO; GO:0032784; P:regulation of DNA-templated transcription, elongation; ISO:MGI.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
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 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 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"
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