THOC5_MOUSE
ID THOC5_MOUSE Reviewed; 683 AA.
AC Q8BKT7; Q69ZU0; Q8CHR3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=THO complex subunit 5 homolog;
DE AltName: Full=Fms-interacting protein;
DE Short=FMIP {ECO:0000303|PubMed:15221008};
GN Name=Thoc5; Synonyms=Fmip, Kiaa0983;
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 [MRNA], INTERACTION WITH CSF1R, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=10597251; DOI=10.1038/sj.onc.1203062;
RA Tamura T., Mancini A., Joos H., Koch A., Hakim C., Dumanski J.,
RA Weidner K.M., Niemann H.;
RT "FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage
RT differentiation.";
RL Oncogene 18:6488-6495(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 37-683.
RC TISSUE=Spleen;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 5-SER-SER-6 AND 8-LYS-ARG-9, AND
RP PHOSPHORYLATION AT SER-5 AND SER-6.
RX PubMed=15221008; DOI=10.1038/sj.onc.1207841;
RA Mancini A., Koch A., Whetton A.D., Tamura T.;
RT "The M-CSF receptor substrate and interacting protein FMIP is governed in
RT its subcellular localization by protein kinase C-mediated phosphorylation,
RT and thereby potentiates M-CSF-mediated differentiation.";
RL Oncogene 23:6581-6589(2004).
RN [6]
RP PHOSPHORYLATION AT THR-328, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15451025; DOI=10.1016/j.cellsig.2004.05.013;
RA Gridley S., Lane W.S., Garner C.W., Lienhard G.E.;
RT "Novel insulin-elicited phosphoproteins in adipocytes.";
RL Cell. Signal. 17:59-66(2005).
RN [7]
RP FUNCTION, AND INTERACTION WITH THOC1.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307; SER-312 AND SER-314, AND
RP IDENTIFICATION BY 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 [9]
RP FUNCTION, INDUCTION, COMPLEX FORMATION WITH CEBPB, AND PHOSPHORYLATION AT
RP TYR-225.
RX PubMed=19015024; DOI=10.1016/j.cellsig.2008.10.018;
RA Carney L., Pierce A., Rijnen M., Gonzalez Sanchez M.B., Hamzah H.G.,
RA Zhang L., Tamura T., Whetton A.D.;
RT "THOC5 couples M-CSF receptor signaling to transcription factor
RT expression.";
RL Cell. Signal. 21:309-316(2009).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20051105; DOI=10.1186/1741-7007-8-1;
RA Mancini A., Niemann-Seyde S.C., Pankow R., El Bounkari O.,
RA Klebba-Faerber S., Koch A., Jaworska E., Spooncer E., Gruber A.D.,
RA Whetton A.D., Tamura T.;
RT "THOC5/FMIP, an mRNA export TREX complex protein, is essential for
RT hematopoietic primitive cell survival in vivo.";
RL BMC Biol. 8:1-1(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307; SER-312; SER-314 AND
RP THR-328, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and
RC Testis;
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: Acts as component of the THO subcomplex of the TREX complex
CC which is thought to couple mRNA transcription, processing and nuclear
CC export, and which specifically associates with spliced mRNA and not
CC with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a
CC transcription-independent mechanism, binds to mRNA upstream of the
CC exon-junction complex (EJC) and is recruited in a splicing- and cap-
CC dependent manner to a region near the 5' end of the mRNA where it
CC functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway.
CC THOC5 in conjunction with ALYREF/THOC4 functions in NXF1-NXT1 mediated
CC nuclear export of HSP70 mRNA; both proteins enhance the RNA binding
CC activity of NXF1 and are required for NXF1 localization to the nuclear
CC rim. Involved in transcription elongation and genome stability.
CC Involved in alternative polyadenylation site choice by recruiting CPSF6
CC to 5' region of target genes; probably mediates association of the TREX
CC and CFIm complexes.
CC -!- FUNCTION: Regulates the expression of myeloid transcription factors
CC CEBPA, CEBPB and GAB2 by enhancing the levels of phosphatidylinositol
CC 3,4,5-trisphosphate. May be involved in the differentiation of
CC granulocytes and adipocytes. Essential for hematopoietic primitive cell
CC survival and plays an integral role in monocytic development.
CC -!- SUBUNIT: Interacts with phosphorylated CSF1R (PubMed:10597251).
CC Component of the THO complex, which is composed of THOC1, THOC2, THOC3,
CC THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B,
CC SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX)
CC complex which seems to have a dynamic structure involving ATP-dependent
CC remodeling. Interacts with ALYREF/THOC4, and THOC7. Interacts (via N-
CC terminus) with the NTF2 domain of NXF1 (By similarity). Forms a complex
CC with CEBPB (PubMed:19015024). Interacts with CPSF6; indicative for an
CC association with the cleavage factor Im (CFIm) complex (By similarity).
CC Interacts with THOC1 (PubMed:16909111). Interacts with LUZP4 (By
CC similarity). Interacts with NCBP3 (By similarity).
CC {ECO:0000250|UniProtKB:Q13769, ECO:0000269|PubMed:10597251,
CC ECO:0000269|PubMed:16909111}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15221008}. Cytoplasm
CC {ECO:0000269|PubMed:15221008}. Note=Shuttles between nucleus and
CC cytoplasm. {ECO:0000250|UniProtKB:Q13769}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC testis, liver and heart. {ECO:0000269|PubMed:10597251,
CC ECO:0000269|PubMed:15451025}.
CC -!- INDUCTION: Up-regulated following CSF1 stimulation.
CC {ECO:0000269|PubMed:19015024}.
CC -!- PTM: Phosphorylated on tyrosine upon binding to activated CSF1R; which
CC causes a dissociation of the two proteins. Phosphorylation on Ser-5
CC and/or Ser-6 is required for nuclear export. Phosphorylated on Thr-328
CC in insulin-stimulated adipocytes. {ECO:0000269|PubMed:10597251,
CC ECO:0000269|PubMed:15221008, ECO:0000269|PubMed:15451025,
CC ECO:0000269|PubMed:19015024}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality seen before day 5.5 of
CC embryonic development (E5.5). {ECO:0000269|PubMed:20051105}.
CC -!- SIMILARITY: Belongs to the THOC5 family. {ECO:0000305}.
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DR EMBL; AK050734; BAC34398.1; -; mRNA.
DR EMBL; BC039758; AAH39758.1; -; mRNA.
DR EMBL; AK173078; BAD32356.1; -; mRNA.
DR CCDS; CCDS24393.1; -.
DR RefSeq; NP_766026.1; NM_172438.3.
DR AlphaFoldDB; Q8BKT7; -.
DR SMR; Q8BKT7; -.
DR BioGRID; 223611; 5.
DR IntAct; Q8BKT7; 2.
DR STRING; 10090.ENSMUSP00000045580; -.
DR iPTMnet; Q8BKT7; -.
DR PhosphoSitePlus; Q8BKT7; -.
DR EPD; Q8BKT7; -.
DR jPOST; Q8BKT7; -.
DR MaxQB; Q8BKT7; -.
DR PaxDb; Q8BKT7; -.
DR PeptideAtlas; Q8BKT7; -.
DR PRIDE; Q8BKT7; -.
DR ProteomicsDB; 259020; -.
DR DNASU; 107829; -.
DR GeneID; 107829; -.
DR KEGG; mmu:107829; -.
DR UCSC; uc007hvl.1; mouse.
DR CTD; 8563; -.
DR MGI; MGI:1351333; Thoc5.
DR eggNOG; KOG2216; Eukaryota.
DR InParanoid; Q8BKT7; -.
DR OrthoDB; 1048314at2759; -.
DR PhylomeDB; Q8BKT7; -.
DR TreeFam; TF314812; -.
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; 107829; 23 hits in 75 CRISPR screens.
DR ChiTaRS; Thoc5; mouse.
DR PRO; PR:Q8BKT7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BKT7; protein.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA: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:0003729; F:mRNA binding; IMP:MGI.
DR GO; GO:0001824; P:blastocyst development; IMP:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0030224; P:monocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006406; P:mRNA export from nucleus; ISO:MGI.
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:0045650; P:negative regulation of macrophage differentiation; IDA:MGI.
DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; ISS:UniProtKB.
DR GO; GO:0060215; P:primitive hemopoiesis; IMP:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0010793; P:regulation of mRNA export from nucleus; IMP:MGI.
DR GO; GO:2000035; P:regulation of stem cell division; IMP:MGI.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0017145; P:stem cell division; IMP:MGI.
DR GO; GO:0046784; P:viral mRNA export from host cell nucleus; ISO:MGI.
DR InterPro; IPR019163; THO_Thoc5.
DR PANTHER; PTHR13375; PTHR13375; 1.
DR Pfam; PF09766; FmiP_Thoc5; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Differentiation; Isopeptide bond; mRNA processing;
KW mRNA splicing; mRNA transport; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13769"
FT CHAIN 2..683
FT /note="THO complex subunit 5 homolog"
FT /id="PRO_0000310555"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..199
FT /note="Interaction with THOC7"
FT /evidence="ECO:0000250|UniProtKB:Q13769"
FT REGION 2..144
FT /note="Interaction with CSF1R"
FT /evidence="ECO:0000269|PubMed:10597251"
FT REGION 299..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 7..10
FT /note="Nuclear localization signal"
FT COMPBIAS 317..336
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13769"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15221008"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15221008"
FT MOD_RES 225
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:19015024"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15451025,
FT ECO:0007744|PubMed:21183079"
FT CROSSLNK 153
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13769"
FT MUTAGEN 5..6
FT /note="SS->AA: Enhances nuclear localization."
FT /evidence="ECO:0000269|PubMed:15221008"
FT MUTAGEN 5..6
FT /note="SS->EE: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:15221008"
FT MUTAGEN 8..9
FT /note="KR->TG: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:15221008"
FT CONFLICT 80
FT /note="V -> L (in Ref. 2; BAC34398)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="T -> A (in Ref. 3; AAH39758)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 683 AA; 78686 MW; 08B795B688AE09CA CRC64;
MSSESSKKRK PKVIRSDGTP TEGKRNRSDT EQEGKYYSEE AEVDLRDPGR DYELYKYTCQ
ELQRLMAEIQ DLKSKGSKDV AIEIEERRIQ SCVHFMTLKK LNRLAHIRLK KGRDQTHEAK
QKVDAYHLQL QNLLYEVMHL QKEITKCLEF KSKHEEIDLV SLEEFYSEAP PSISKAEITM
GDPHQQTLAR LDWELEQRKR LAEKYRECLS NKEKILKEIE VKRDYLSSLQ PRLNSIMQAS
LPVQEYLFMP FDQAHKQYET ARHLPPPLYV LFVQATAYGQ ACDKTLSVAI EGSVDEAKAL
FKPPEDSQDD ESDSDAEEEQ TTKRRRPTLG VQLDDKRKEM LKRHPLSVLL DLKCKDNSVL
HLTFYYLMNL NIMTVKAKVT TAVELITPIS AGDLLSPDSV LSCLYPGDHG KKTPNPANQY
QFDKVGILTL RDYVLELGHP YLWVQKLGGL HFPKEQPQQT VMPDHSQSAS HMETTMKLLK
TRVQSRLALH KQFASLEHGI VPVTSDCQDL FPAKVVSRLV KWVIITHEDY MELHFTKDIV
EAGLAGDTNL YYLALIERGT AKLQAAVVLN PGYSSIPPVF RLCLNWKGEK TNSNDDNIRA
MESEVNVCYK ELCGPRPSHQ LLTNQLQRLC VLLDVYLETE SHDDSFEGPK EFPQEKMCLR
LFRGPSRMKP FKYNHPQGFF SHR
