THOC4_HUMAN
ID THOC4_HUMAN Reviewed; 257 AA.
AC Q86V81; O43672;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=THO complex subunit 4;
DE Short=Tho4;
DE AltName: Full=Ally of AML-1 and LEF-1;
DE AltName: Full=Aly/REF export factor;
DE AltName: Full=Transcriptional coactivator Aly/REF;
DE AltName: Full=bZIP-enhancing factor BEF;
GN Name=ALYREF; Synonyms=ALY, BEF, THOC4;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 PROTEIN SEQUENCE OF 2-15 AND 146-156, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Quadroni M.;
RL Submitted (OCT-2004) to UniProtKB.
RN [4]
RP PROTEIN SEQUENCE OF 2-14; 108-134; 145-155; 165-189; 203-216 AND 236-253,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, METHYLATION AT
RP ARG-204 AND ARG-220, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-257, AND INVOLVEMENT IN SYSTEMIC LUPUS
RP ERYTHEMATOSUS.
RC TISSUE=Cervix carcinoma;
RX PubMed=9952027; DOI=10.1016/s0198-8859(98)00085-8;
RA Wichmann I., Garcia-Lozano J.R., Respaldiza N., Gonzalez-Escribano M.F.,
RA Nunez-Roldan A.;
RT "Autoantibodies to transcriptional regulation proteins DEK and ALY in a
RT patient with systemic lupus erythematosus.";
RL Hum. Immunol. 60:57-62(1999).
RN [6]
RP PROTEIN SEQUENCE OF 108-133, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP INTERACTION WITH THE SPLICEOSOME.
RX PubMed=12176931; DOI=10.1101/gr.473902;
RA Rappsilber J., Ryder U., Lamond A.I., Mann M.;
RT "Large-scale proteomic analysis of the human spliceosome.";
RL Genome Res. 12:1231-1245(2002).
RN [7]
RP PROTEIN SEQUENCE OF 127-131; 182-189; 239-245 AND 249-251, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10488337; DOI=10.1016/s1097-2765(00)80369-x;
RA Virbasius C.-M., Wagner S., Green M.R.;
RT "A human nuclear-localized chaperone that regulates dimerization, DNA
RT binding, and transcriptional activity of bZIP proteins.";
RL Mol. Cell 4:219-228(1999).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP INTERACTION WITH THE SPLICEOSOME.
RX PubMed=9731529; DOI=10.1038/1700;
RA Neubauer G., King A., Rappsilber J., Calvio C., Watson M., Ajuh P.,
RA Sleeman J., Lamond A.I., Mann M.;
RT "Mass spectrometry and EST-database searching allows characterization of
RT the multi-protein spliceosome complex.";
RL Nat. Genet. 20:46-50(1998).
RN [9]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX (EJC)
RP WITH DEK; RBM8A; RNPS1 AND SRRM1.
RX PubMed=11118221; DOI=10.1093/emboj/19.24.6860;
RA Le Hir H., Izaurralde E., Maquat L.E., Moore M.J.;
RT "The spliceosome deposits multiple proteins 20-24 nucleotides upstream of
RT mRNA exon-exon junctions.";
RL EMBO J. 19:6860-6869(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH RBM8A; NXF1 AND THE EXON JUNCTION COMPLEX.
RX PubMed=11707413; DOI=10.1093/emboj/20.22.6424;
RA Kataoka N., Diem M.D., Kim V.N., Yong J., Dreyfuss G.;
RT "Magoh, a human homolog of Drosophila mago nashi protein, is a component of
RT the splicing-dependent exon-exon junction complex.";
RL EMBO J. 20:6424-6433(2001).
RN [11]
RP FUNCTION, AND INTERACTION WITH NXF1.
RX PubMed=11675789; DOI=10.1038/35098106;
RA Luo M.-J., Zhou Z., Magni K., Christoforides C., Rappsilber J., Mann M.,
RA Reed R.;
RT "Pre-mRNA splicing and mRNA export linked by direct interactions between
RT UAP56 and Aly.";
RL Nature 413:644-647(2001).
RN [12]
RP IDENTIFICATION IN A MRNP COMPLEX WITH UPF3A AND UPF3B.
RX PubMed=11546873; DOI=10.1126/science.1062829;
RA Kim V.N., Kataoka N., Dreyfuss G.;
RT "Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent
RT exon-exon junction complex.";
RL Science 293:1832-1836(2001).
RN [13]
RP FUNCTION, AND INTERACTION WITH HHV-1 ICP27.
RX PubMed=12438613; DOI=10.1128/jvi.76.24.12877-12889.2002;
RA Chen I.-H.B., Sciabica K.S., Sandri-Goldin R.M.;
RT "ICP27 interacts with the RNA export factor Aly/REF to direct herpes
RT simplex virus type 1 intronless mRNAs to the TAP export pathway.";
RL J. Virol. 76:12877-12889(2002).
RN [14]
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SPLICEOSOMAL
RP C COMPLEX.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [16]
RP INTERACTION WITH DDX39B; RBM8A; RNPS1 AND SRRM1.
RX PubMed=12944400; DOI=10.1074/jbc.m306856200;
RA McCracken S., Longman D., Johnstone I.L., Caceres J.F., Blencowe B.J.;
RT "An evolutionarily conserved role for SRm160 in 3'-end processing that
RT functions independently of exon junction complex formation.";
RL J. Biol. Chem. 278:44153-44160(2003).
RN [17]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-204, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=15782174; DOI=10.1038/nmeth715;
RA Ong S.E., Mittler G., Mann M.;
RT "Identifying and quantifying in vivo methylation sites by heavy methyl
RT SILAC.";
RL Nat. Methods 1:119-126(2004).
RN [18]
RP INTERACTION WITH EIF4A3 AND NXF1.
RX PubMed=14730019; DOI=10.1261/rna.5230104;
RA Chan C.C., Dostie J., Diem M.D., Feng W., Mann M., Rappsilber J.,
RA Dreyfuss G.;
RT "eIF4A3 is a novel component of the exon junction complex.";
RL RNA 10:200-209(2004).
RN [19]
RP IDENTIFICATION IN THE TREX COMPLEX, FUNCTION OF THE TREX COMPLEX, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 [20]
RP IDENTIFICATION IN THE TREX COMPLEX, FUNCTION OF THE TREX COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH DDX39B.
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 [21]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX,
RP HETERODIMERIZATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [22]
RP FUNCTION OF THE TREX COMPLEX, AND INTERACTION WITH NCBP1.
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 [23]
RP INTERACTION WITH IWS1 AND EXOSC10.
RX PubMed=17234882; DOI=10.1101/gad.1503107;
RA Yoh S.M., Cho H., Pickle L., Evans R.M., Jones K.A.;
RT "The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA
RT splicing and export.";
RL Genes Dev. 21:160-174(2007).
RN [24]
RP FUNCTION, AND INTERACTION WITH DDX39B.
RX PubMed=17984224; DOI=10.1128/mcb.01341-07;
RA Taniguchi I., Ohno M.;
RT "ATP-dependent recruitment of export factor Aly/REF onto intronless mRNAs
RT by RNA helicase UAP56.";
RL Mol. Cell. Biol. 28:601-608(2008).
RN [25]
RP FUNCTION OF THE TREX COMPLEX, SUBUNIT, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH NXF1; DDX39B AND HUMAN KAPOSI'S SARCOMA-ASSOCIATED
RP HERPESVIRUS ORF57 PROTEIN.
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 [26]
RP IDENTIFICATION BY 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 [27]
RP FUNCTION.
RX PubMed=18364396; DOI=10.1073/pnas.0709167105;
RA Hautbergue G.M., Hung M.L., Golovanov A.P., Lian L.Y., Wilson S.A.;
RT "Mutually exclusive interactions drive handover of mRNA from export
RT adaptors to TAP.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5154-5159(2008).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [29]
RP FUNCTION, AND INTERACTION WITH THOC5 AND NXF1.
RX PubMed=19165146; DOI=10.1038/emboj.2009.5;
RA Katahira J., Inoue H., Hurt E., Yoneda Y.;
RT "Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear
RT export of HSP70 mRNA.";
RL EMBO J. 28:556-567(2009).
RN [30]
RP INTERACTION WITH RBM15B.
RX PubMed=19586903; DOI=10.1074/jbc.m109.040113;
RA Uranishi H., Zolotukhin A.S., Lindtner S., Warming S., Zhang G.M., Bear J.,
RA Copeland N.G., Jenkins N.A., Pavlakis G.N., Felber B.K.;
RT "The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the
RT nuclear export receptor NXF1.";
RL J. Biol. Chem. 284:26106-26116(2009).
RN [31]
RP SUBCELLULAR LOCATION.
RX PubMed=19324961; DOI=10.1261/rna.1387009;
RA Schmidt U., Im K.-B., Benzing C., Janjetovic S., Rippe K., Lichter P.,
RA Wachsmuth M.;
RT "Assembly and mobility of exon-exon junction complexes in living cells.";
RL RNA 15:862-876(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP METHYLATION, AND MRNA-BINDING.
RX PubMed=20129943; DOI=10.1093/nar/gkq033;
RA Hung M.L., Hautbergue G.M., Snijders A.P., Dickman M.J., Wilson S.A.;
RT "Arginine methylation of REF/ALY promotes efficient handover of mRNA to
RT TAP/NXF1.";
RL Nucleic Acids Res. 38:3351-3361(2010).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-94 AND SER-239, AND
RP IDENTIFICATION BY MASS 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [35]
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 [36]
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 [37]
RP INTERACTION WITH HUMAN KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS ORF57
RP PROTEIN, AND INTERACTION WITH HUMAN HERPESVIRUS 1 ICP27 PROTEIN.
RX PubMed=21253573; DOI=10.1371/journal.ppat.1001244;
RA Tunnicliffe R.B., Hautbergue G.M., Kalra P., Jackson B.R., Whitehouse A.,
RA Wilson S.A., Golovanov A.P.;
RT "Structural basis for the recognition of cellular mRNA export factor REF by
RT herpes viral proteins HSV-1 ICP27 and HVS ORF57.";
RL PLoS Pathog. 7:E1001244-E1001244(2011).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [39]
RP FUNCTION.
RX PubMed=22893130; DOI=10.1038/ncomms2005;
RA Viphakone N., Hautbergue G.M., Walsh M., Chang C.T., Holland A.,
RA Folco E.G., Reed R., Wilson S.A.;
RT "TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.";
RL Nat. Commun. 3:1006-1006(2012).
RN [40]
RP ERRATUM OF PUBMED:22893130.
RX DOI=10.1038/ncomms3377;
RA Viphakone N., Hautbergue G.M., Walsh M., Chang C.T., Holland A.,
RA Folco E.G., Reed R., Wilson S.A.;
RL Nat. Commun. 4:2377-2377(2013).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-94 AND SER-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE 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 [43]
RP FUNCTION, AND INTERACTION WITH THOC1 AND THOC2.
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 [44]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NXF1 AND CHTOP.
RX PubMed=23826332; DOI=10.1371/journal.pone.0067676;
RA Teng I.F., Wilson S.A.;
RT "Mapping interactions between mRNA export factors in living cells.";
RL PLoS ONE 8:E67676-E67676(2013).
RN [45]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [46]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-38; ARG-58; ARG-63; ARG-71;
RP ARG-204 AND LYS-235, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [47]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [48]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [49]
RP FUNCTION, SUBCELLULAR LOCATION, AND RNA-BINDING.
RX PubMed=28418038; DOI=10.1038/cr.2017.55;
RA Yang X., Yang Y., Sun B.F., Chen Y.S., Xu J.W., Lai W.Y., Li A., Wang X.,
RA Bhattarai D.P., Xiao W., Sun H.Y., Zhu Q., Ma H.L., Adhikari S., Sun M.,
RA Hao Y.J., Zhang B., Huang C.M., Huang N., Jiang G.B., Zhao Y.L., Wang H.L.,
RA Sun Y.P., Yang Y.G.;
RT "5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and
RT ALYREF as an m5C reader.";
RL Cell Res. 27:606-625(2017).
CC -!- FUNCTION: Export adapter involved in nuclear export of spliced and
CC unspliced mRNA. Binds mRNA which is thought to be transferred to the
CC NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway) (PubMed:15833825,
CC PubMed:15998806, PubMed:17190602, PubMed:11707413, PubMed:11675789,
CC PubMed:11979277, PubMed:18364396, PubMed:22144908, PubMed:22893130,
CC PubMed:23222130, PubMed:25662211). Component of the TREX complex which
CC is thought to couple mRNA transcription, processing and nuclear export,
CC and specifically associates with spliced mRNA and not with unspliced
CC pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX is
CC recruited to spliced mRNAs by a transcription-independent mechanism,
CC binds to mRNA upstream of the exon-junction complex (EJC) and is
CC recruited in a splicing- and cap-dependent manner to a region near the
CC 5' end of the mRNA where it functions in mRNA export to the cytoplasm
CC (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX recruitment
CC occurs via an interaction between ALYREF/THOC4 and the cap-binding
CC protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602). The
CC TREX complex is essential for the export of Kaposi's sarcoma-associated
CC herpesvirus (KSHV) intronless mRNAs and infectious virus production;
CC ALYREF/THOC4 mediates the recruitment of the TREX complex to the
CC intronless viral mRNA (PubMed:18974867). Required for TREX complex
CC assembly and for linking DDX39B to the cap-binding complex (CBC)
CC (PubMed:15998806, PubMed:17984224). In conjunction with THOC5 functions
CC in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins
CC enhance the RNA binding activity of NXF1 and are required for NXF1
CC localization to the nuclear rim (PubMed:19165146). Involved in the
CC nuclear export of intronless mRNA; proposed to be recruited to
CC intronless mRNA by ATP-bound DDX39B. Involved in transcription
CC elongation and genome stability (PubMed:12438613, PubMed:17984224).
CC Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs:
CC specifically recognizes and binds m5C mRNAs and mediates their nucleo-
CC cytoplasmic shuttling (PubMed:28418038). {ECO:0000269|PubMed:11675789,
CC ECO:0000269|PubMed:11707413, ECO:0000269|PubMed:11979277,
CC ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:15833825,
CC ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602,
CC ECO:0000269|PubMed:17984224, ECO:0000269|PubMed:18364396,
CC ECO:0000269|PubMed:18974867, ECO:0000269|PubMed:19165146,
CC ECO:0000269|PubMed:22144908, ECO:0000269|PubMed:22893130,
CC ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:25662211,
CC ECO:0000269|PubMed:28418038}.
CC -!- FUNCTION: Acts as chaperone and promotes the dimerization of
CC transcription factors containing basic leucine zipper (bZIP) domains
CC and thereby promotes transcriptional activation.
CC {ECO:0000269|PubMed:10488337}.
CC -!- SUBUNIT: Homomultimer. Is part of several complexes involved in mRNA
CC processing and export. Component of the transcription/export (TREX)
CC complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP
CC and the THO subcomplex; TREX seems to have a dynamic structure
CC involving ATP-dependent remodeling; in the complex interacts (via C-
CC terminus) directly with DDX39B and interacts directly with THOC1 and
CC THOC2. Found in mRNA splicing-dependent exon junction complexes (EJC).
CC Identified in the spliceosome C complex. Found in a mRNP complex with
CC UPF3A and UPF3B. Interacts with RBM8A, NCBP1, THOC5, LEF1, RUNX1,
CC EIF4A3, RNPS1, SRRM1, IWS1 and EXOSC1. Interacts with RBM15B
CC (PubMed:19586903). Interacts with NXF1; the interaction is direct.
CC {ECO:0000269|PubMed:11118221, ECO:0000269|PubMed:11546873,
CC ECO:0000269|PubMed:11675789, ECO:0000269|PubMed:11707413,
CC ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:12176931, ECO:0000269|PubMed:12944400,
CC ECO:0000269|PubMed:14730019, ECO:0000269|PubMed:15833825,
CC ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:16314458,
CC ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:17234882,
CC ECO:0000269|PubMed:17984224, ECO:0000269|PubMed:18974867,
CC ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:19586903,
CC ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:23826332,
CC ECO:0000269|PubMed:9731529}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human Kaposi's sarcoma-
CC associated herpesvirus (HHV-8) ORF57 protein; this interaction allows
CC efficient export of HHV-8 early and late intronless transcripts.
CC {ECO:0000269|PubMed:18974867, ECO:0000269|PubMed:21253573}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HHV-1 ICP27 protein; this
CC interaction recruits ALYREF to viral replication compartments and
CC probably directs viral mRNA to the TAP/NFX1 pathway.
CC {ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:21253573}.
CC -!- INTERACTION:
CC Q86V81; P31749: AKT1; NbExp=5; IntAct=EBI-347640, EBI-296087;
CC Q86V81; P06493: CDK1; NbExp=4; IntAct=EBI-347640, EBI-444308;
CC Q86V81; Q9Y3Y2: CHTOP; NbExp=8; IntAct=EBI-347640, EBI-347794;
CC Q86V81; Q13838: DDX39B; NbExp=4; IntAct=EBI-347640, EBI-348622;
CC Q86V81; Q9UBU9: NXF1; NbExp=4; IntAct=EBI-347640, EBI-398874;
CC Q86V81; Q2HR75: ORF57; Xeno; NbExp=4; IntAct=EBI-347640, EBI-6884751;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10488337,
CC ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332,
CC ECO:0000269|PubMed:28418038, ECO:0000305|PubMed:18974867}. Nucleus
CC speckle {ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}.
CC Cytoplasm {ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:28418038}.
CC Note=Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and DDX39B in
CC the nucleus and nuclear speckles. Travels to the cytoplasm as part of
CC the exon junction complex (EJC) bound to mRNA (PubMed:19324961).
CC Localizes to regions surrounding nuclear speckles known as perispeckles
CC in which TREX complex assembly seems to occur (PubMed:23826332).
CC {ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}.
CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of cancer types.
CC {ECO:0000269|PubMed:25662211}.
CC -!- PTM: Arg-204 is dimethylated, probably to asymmetric dimethylarginine.
CC Arginine methylation reduces RNA binding. {ECO:0000269|PubMed:20129943,
CC ECO:0000269|Ref.4}.
CC -!- PTM: Citrullinated by PADI4. {ECO:0000250}.
CC -!- MISCELLANEOUS: Antibodies against ALYREF/THOC4 are found in sera of
CC patients with systemic lupus erythematosus (SLE).
CC -!- SIMILARITY: Belongs to the ALYREF family. {ECO:0000305}.
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DR EMBL; AC145207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052302; AAH52302.1; -; mRNA.
DR EMBL; AF047002; AAD09608.1; -; mRNA.
DR RefSeq; NP_005773.3; NM_005782.3.
DR PDB; 3ULH; X-ray; 2.54 A; A=78-183.
DR PDBsum; 3ULH; -.
DR AlphaFoldDB; Q86V81; -.
DR SMR; Q86V81; -.
DR BioGRID; 115486; 318.
DR CORUM; Q86V81; -.
DR DIP; DIP-32711N; -.
DR IntAct; Q86V81; 135.
DR MINT; Q86V81; -.
DR STRING; 9606.ENSP00000421592; -.
DR ChEMBL; CHEMBL4296014; -.
DR iPTMnet; Q86V81; -.
DR MetOSite; Q86V81; -.
DR PhosphoSitePlus; Q86V81; -.
DR BioMuta; ALYREF; -.
DR DMDM; 48429165; -.
DR EPD; Q86V81; -.
DR jPOST; Q86V81; -.
DR MassIVE; Q86V81; -.
DR MaxQB; Q86V81; -.
DR PaxDb; Q86V81; -.
DR PeptideAtlas; Q86V81; -.
DR PRIDE; Q86V81; -.
DR ProteomicsDB; 69973; -.
DR TopDownProteomics; Q86V81; -.
DR ABCD; Q86V81; 1 sequenced antibody.
DR DNASU; 10189; -.
DR GeneID; 10189; -.
DR KEGG; hsa:10189; -.
DR CTD; 10189; -.
DR DisGeNET; 10189; -.
DR GeneCards; ALYREF; -.
DR HGNC; HGNC:19071; ALYREF.
DR MIM; 604171; gene.
DR neXtProt; NX_Q86V81; -.
DR PharmGKB; PA134925107; -.
DR eggNOG; KOG0533; Eukaryota.
DR InParanoid; Q86V81; -.
DR OrthoDB; 1369069at2759; -.
DR PhylomeDB; Q86V81; -.
DR PathwayCommons; Q86V81; -.
DR Reactome; R-HSA-159227; Transport of the SLBP independent Mature mRNA.
DR Reactome; R-HSA-159230; Transport of the SLBP Dependant Mature mRNA.
DR Reactome; R-HSA-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR SignaLink; Q86V81; -.
DR SIGNOR; Q86V81; -.
DR BioGRID-ORCS; 10189; 685 hits in 1089 CRISPR screens.
DR ChiTaRS; ALYREF; human.
DR GeneWiki; THOC4; -.
DR GenomeRNAi; 10189; -.
DR Pharos; Q86V81; Tbio.
DR PRO; PR:Q86V81; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q86V81; protein.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000346; C:transcription export complex; IDA:UniProtKB.
DR GO; GO:0062153; F:C5-methylcytidine-containing RNA binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006406; P:mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; HDA: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:0031297; P:replication fork processing; IMP:UniProtKB.
DR GO; GO:0006405; P:RNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0046784; P:viral mRNA export from host cell nucleus; IDA:UniProtKB.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR025715; FoP_C.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF13865; FoP_duplication; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM01218; FoP_duplication; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chaperone; Citrullination; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Methylation;
KW mRNA processing; mRNA splicing; mRNA transport; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Spliceosome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.3, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"
FT CHAIN 2..257
FT /note="THO complex subunit 4"
FT /id="PRO_0000081974"
FT DOMAIN 106..183
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 16..37
FT /note="Sufficient for RNA-binding, interaction with NXF1-
FT NXT1 heterodimer"
FT REGION 85..186
FT /note="Interaction with HHV-8 ORF57 protein and with ICP27
FT from HHV-1"
FT /evidence="ECO:0000250"
FT REGION 187..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.3, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 38
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08583"
FT MOD_RES 38
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 58
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 63
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 71
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08583"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 141
FT /note="Citrulline"
FT /evidence="ECO:0000250"
FT MOD_RES 197
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08583"
FT MOD_RES 197
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08583"
FT MOD_RES 204
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 204
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:15782174"
FT MOD_RES 204
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|Ref.4"
FT MOD_RES 220
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000269|Ref.4"
FT MOD_RES 235
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT CONFLICT 26
FT /note="G -> R (in Ref. 5; AAD09608)"
FT /evidence="ECO:0000305"
FT CONFLICT 35..36
FT /note="QG -> RA (in Ref. 5; AAD09608)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="G -> R (in Ref. 5; AAD09608)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="D -> N (in Ref. 5; AAD09608)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="V -> F (in Ref. 5; AAD09608)"
FT /evidence="ECO:0000305"
FT STRAND 105..112
FT /evidence="ECO:0007829|PDB:3ULH"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:3ULH"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:3ULH"
FT STRAND 145..155
FT /evidence="ECO:0007829|PDB:3ULH"
FT HELIX 156..166
FT /evidence="ECO:0007829|PDB:3ULH"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:3ULH"
SQ SEQUENCE 257 AA; 26888 MW; E2B5021DA579919A CRC64;
MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG GAQAAARVNR GGGPIRNRPA
IARGAAGGGG RNRPAPYSRP KQLPDKWQHD LFDSGFGGGA GVETGGKLLV SNLDFGVSDA
DIQELFAEFG TLKKAAVHYD RSGRSLGTAD VHFERKADAL KAMKQYNGVP LDGRPMNIQL
VTSQIDAQRR PAQSVNRGGM TRNRGAGGFG GGGGTRRGTR GGARGRGRGA GRNSKQQLSA
EELDAQLDAY NARMDTS
