ID U2AF2_HUMAN Reviewed; 475 AA. AC P26368; Q96HC5; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 05-DEC-2018, entry version 211. DE RecName: Full=Splicing factor U2AF 65 kDa subunit; DE AltName: Full=U2 auxiliary factor 65 kDa subunit; DE Short=hU2AF(65); DE Short=hU2AF65; DE AltName: Full=U2 snRNP auxiliary factor large subunit; GN Name=U2AF2; Synonyms=U2AF65; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1538748; DOI=10.1038/355609a0; RA Zamore P.D., Patton J.G., Green M.R.; RT "Cloning and domain structure of the mammalian splicing factor U2AF."; RL Nature 355:609-614(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lymph, and Skin; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 2-9; 196-203; 277-286 AND 463-471, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.; RL Submitted (NOV-2006) to UniProtKB. RN [5] RP PROTEIN SEQUENCE OF 261-286, 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 [6] RP INTERACTION WITH ZRSR2. RX PubMed=9237760; DOI=10.1038/41137; RA Tronchere H., Wang J., Fu X.D.; RT "A protein related to splicing factor U2AF35 that interacts with RT U2AF65 and SR proteins in splicing of pre-mRNA."; RL Nature 388:397-400(1997). RN [7] RP INTERACTION WITH SCAF11. RX PubMed=9447963; DOI=10.1128/MCB.18.2.676; RA Zhang W.-J., Wu J.Y.; RT "Sip1, a novel RS domain-containing protein essential for pre-mRNA RT splicing."; RL Mol. Cell. Biol. 18:676-684(1998). RN [8] RP INTERACTION WITH SF1. RX PubMed=10449420; DOI=10.1093/emboj/18.16.4549; RA Wang X., Bruderer S., Rafi Z., Xue J., Milburn P.J., Kraemer A., RA Robinson P.J.; RT "Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent RT protein kinase regulates spliceosome assembly."; RL EMBO J. 18:4549-4559(1999). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., RA Mann M.; RT "Proteomic characterization of the human centrosome by protein RT correlation profiling."; RL Nature 426:570-574(2003). RN [10] RP FUNCTION. RX PubMed=15009664; DOI=10.1046/j.1471-4159.2003.02232.x; RA Wang J., Gao Q.S., Wang Y., Lafyatis R., Stamm S., Andreadis A.; RT "Tau exon 10, whose missplicing causes frontotemporal dementia, is RT regulated by an intricate interplay of cis elements and trans RT factors."; RL J. Neurochem. 88:1078-1090(2004). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [12] RP FUNCTION, INTERACTION WITH CPSF7, AND DOMAIN. RX PubMed=17024186; DOI=10.1038/sj.emboj.7601331; RA Millevoi S., Loulergue C., Dettwiler S., Karaa S.Z., Keller W., RA Antoniou M., Vagner S.; RT "An interaction between U2AF 65 and CF I(m) links the splicing and 3' RT end processing machineries."; RL EMBO J. 25:4854-4864(2006). RN [13] RP INTERACTION WITH RBM17. RX PubMed=17589525; DOI=10.1038/nsmb1260; RA Corsini L., Bonnal S., Basquin J., Hothorn M., Scheffzek K., RA Valcarcel J., Sattler M.; RT "U2AF-homology motif interactions are required for alternative RT splicing regulation by SPF45."; RL Nat. Struct. Mol. Biol. 14:620-629(2007). RN [14] 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 [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [16] RP SUBUNIT, AND INTERACTION WITH KHDC4. RX PubMed=19641227; DOI=10.1074/jbc.M109.036632; RA Grillari J., Loescher M., Denegri M., Lee K., Fortschegger K., RA Eisenhaber F., Ajuh P., Lamond A.I., Katinger H., RA Grillari-Voglauer R.; RT "Blom7alpha is a novel heterogeneous nuclear ribonucleoprotein K RT homology domain protein involved in pre-mRNA splicing that interacts RT with SNEVPrp19-Pso4."; RL J. Biol. Chem. 284:29193-29204(2009). RN [17] RP FUNCTION, AND RNA-BINDING. RX PubMed=19470458; DOI=10.1073/pnas.0900342106; RA Warf M.B., Diegel J.V., von Hippel P.H., Berglund J.A.; RT "The protein factors MBNL1 and U2AF65 bind alternative RNA structures RT to regulate splicing."; RL Proc. Natl. Acad. Sci. U.S.A. 106:9203-9208(2009). RN [18] RP IDENTIFICATION BY 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 [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70, AND IDENTIFICATION BY RP 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., RA Walther T.C., 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 FUNCTION, AND HYDROXYLATION AT LYS-15 AND LYS-276. RX PubMed=19574390; DOI=10.1126/science.1175865; RA Webby C.J., Wolf A., Gromak N., Dreger M., Kramer H., Kessler B., RA Nielsen M.L., Schmitz C., Butler D.S., Yates J.R. III, Delahunty C.M., RA Hahn P., Lengeling A., Mann M., Proudfoot N.J., Schofield C.J., RA Boettger A.; RT "Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated RT with RNA splicing."; RL Science 325:90-93(2009). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-2 AND SER-79, CLEAVAGE OF INITIATOR METHIONINE RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] 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., RA Buerckstuemmer T., 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 [23] RP INTERACTION WITH SNW1. RX PubMed=21460037; DOI=10.1101/gad.2002611; RA Chen Y., Zhang L., Jones K.A.; RT "SKIP counteracts p53-mediated apoptosis via selective regulation of RT p21Cip1 mRNA splicing."; RL Genes Dev. 25:701-716(2011). RN [24] RP FUNCTION, AND INTERACTION WITH POLR2A AND PRPF19. RX PubMed=21536736; DOI=10.1101/gad.2038011; RA David C.J., Boyne A.R., Millhouse S.R., Manley J.L.; RT "The RNA polymerase II C-terminal domain promotes splicing activation RT through recruitment of a U2AF65-Prp19 complex."; RL Genes Dev. 25:972-983(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-79 AND SER-294, RP AND 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, AND IDENTIFICATION RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [30] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-70, AND IDENTIFICATION BY RP 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 [31] RP INTERACTION WITH THE SF3B COMPLEX. RX PubMed=27720643; DOI=10.1016/j.molcel.2016.08.036; RA Cretu C., Schmitzova J., Ponce-Salvatierra A., Dybkov O., RA De Laurentiis E.I., Sharma K., Will C.L., Urlaub H., Luehrmann R., RA Pena V.; RT "Molecular architecture of SF3b and structural consequences of its RT cancer-related mutations."; RL Mol. Cell 64:307-319(2016). RN [32] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-15 AND LYS-70, 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- RT modification with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [33] RP STRUCTURE BY NMR OF 148-237. RX PubMed=10449418; DOI=10.1093/emboj/18.16.4523; RA Ito T., Muto Y., Green M.R., Yokoyama S.; RT "Solution structures of the first and second RNA-binding domains of RT human U2 small nuclear ribonucleoprotein particle auxiliary factor RT (U2AF(65))."; RL EMBO J. 18:4523-4534(1999). RN [34] RP STRUCTURE BY NMR OF 372-475 IN COMPLEX WITH SF1, AND MUTAGENESIS OF RP 387-GLU-GLU-388; 391-ASP--GLU-393; 396-GLU-GLU-397 AND PHE-454. RX PubMed=12718882; DOI=10.1016/S1097-2765(03)00115-1; RA Selenko P., Gregorovic G., Sprangers R., Stier G., Rhani Z., RA Kraemer A., Sattler M.; RT "Structural basis for the molecular recognition between human splicing RT factors U2AF65 and SF1/mBBP."; RL Mol. Cell 11:965-976(2003). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 90-112 IN COMPLEX WITH U2AF1, RP AND MUTAGENESIS OF TRP-92; PRO-96 AND PRO-104. RX PubMed=11551507; DOI=10.1016/S0092-8674(01)00480-9; RA Kielkopf C.L., Rodionova N.A., Green M.R., Burley S.K.; RT "A novel peptide recognition mode revealed by the X-ray structure of a RT core U2AF35/U2AF65 heterodimer."; RL Cell 106:595-605(2001). CC -!- FUNCTION: Plays a role in pre-mRNA splicing and 3'-end processing CC (PubMed:17024186). By recruiting PRPF19 and the PRP19C/Prp19 CC complex/NTC/Nineteen complex to the RNA polymerase II C-terminal CC domain (CTD), and thereby pre-mRNA, may couple transcription to CC splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) CC pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 CC inclusion through competition with MBNL1. Binds preferentially to CC a single-stranded structure within the polypyrimidine tract of CC TNNT2 intron 4 during spliceosome assembly. Required for the CC export of mRNA out of the nucleus, even if the mRNA is encoded by CC an intron-less gene. Represses the splicing of MAPT/Tau exon 10. CC Positively regulates pre-mRNA 3'-end processing by recruiting the CC CFIm complex to cleavage and polyadenylation signals CC (PubMed:17024186). {ECO:0000269|PubMed:15009664, CC ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:19470458, CC ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:21536736}. CC -!- SUBUNIT: Interacts with U2AF1L4 (By similarity). Heterodimer with CC U2AF1 (PubMed:11551507). Binds unphosphorylated SF1 CC (PubMed:10449420, PubMed:12718882). Interacts with SCAF11 and SNW1 CC (PubMed:9447963, PubMed:21460037). Interacts with ZRSR2/U2AF1-RS2. CC Interacts with RBM17 (PubMed:17589525). Interacts with PRPF19; the CC interaction is direct. Interacts with POLR2A (via the C-terminal CC domain); recruits PRPF19 and the Prp19 complex to the pre-mRNA CC (PubMed:21536736). Interacts with KHDC4 (Isoform 2) CC (PubMed:19641227). Interacts with ZRSR2 (PubMed:9237760). CC Interacts with the SF3B complex composed of SF3B1, SF3B2, SF3B3, CC SF3B4, SF3B5, SF3B6 and PHF5A (PubMed:27720643). Interacts (via N- CC terminus) with CPSF7 (via C-terminus); this interaction stimulates CC pre-mRNA 3'-end processing by promoting the recruitment of the CC CFIm complex to cleavage and polyadenylation signals CC (PubMed:17024186). {ECO:0000250|UniProtKB:P26369, CC ECO:0000269|PubMed:10449420, ECO:0000269|PubMed:11551507, CC ECO:0000269|PubMed:12176931, ECO:0000269|PubMed:12718882, CC ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:17589525, CC ECO:0000269|PubMed:19641227, ECO:0000269|PubMed:21460037, CC ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:27720643, CC ECO:0000269|PubMed:9237760, ECO:0000269|PubMed:9447963}. CC -!- INTERACTION: CC Q08117:AES; NbExp=3; IntAct=EBI-742339, EBI-717810; CC P54253:ATXN1; NbExp=4; IntAct=EBI-742339, EBI-930964; CC Q8IWX8:CHERP; NbExp=2; IntAct=EBI-742339, EBI-2555370; CC Q8N684:CPSF7; NbExp=2; IntAct=EBI-742339, EBI-746909; CC Q9UI36-2:DACH1; NbExp=3; IntAct=EBI-742339, EBI-10186082; CC Q13838:DDX39B; NbExp=4; IntAct=EBI-11097439, EBI-348622; CC P15941:MUC1; NbExp=2; IntAct=EBI-742339, EBI-2804728; CC O43395:PRPF3; NbExp=2; IntAct=EBI-742339, EBI-744322; CC Q9UHX1:PUF60; NbExp=5; IntAct=EBI-742339, EBI-1053259; CC P98175:RBM10; NbExp=2; IntAct=EBI-742339, EBI-721525; CC Q96I25:RBM17; NbExp=2; IntAct=EBI-742339, EBI-740272; CC P52756:RBM5; NbExp=2; IntAct=EBI-742339, EBI-714003; CC P82979:SARNP; NbExp=3; IntAct=EBI-742339, EBI-347495; CC Q15637:SF1; NbExp=19; IntAct=EBI-742339, EBI-744603; CC P09012:SNRPA; NbExp=5; IntAct=EBI-742339, EBI-607085; CC Q13573:SNW1; NbExp=5; IntAct=EBI-742339, EBI-632715; CC P78362:SRPK2; NbExp=4; IntAct=EBI-742339, EBI-593303; CC Q8IWZ8:SUGP1; NbExp=3; IntAct=EBI-742339, EBI-2691671; CC Q9NVV9:THAP1; NbExp=4; IntAct=EBI-742339, EBI-741515; CC Q01081:U2AF1; NbExp=11; IntAct=EBI-742339, EBI-632461; CC P0DN76:U2AF1L5; NbExp=4; IntAct=EBI-11097439, EBI-14082807; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P26368-1; Sequence=Displayed; CC Name=2; CC IsoId=P26368-2; Sequence=VSP_035414; CC -!- PTM: Lysyl-hydroxylation at Lys-15 and Lys-276 affects the mRNA CC splicing activity of the protein, leading to regulate some, but CC not all, alternative splicing events. CC {ECO:0000269|PubMed:19574390}. CC -!- SIMILARITY: Belongs to the splicing factor SR family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X64044; CAA45409.1; -; mRNA. DR EMBL; CH471135; EAW72404.1; -; Genomic_DNA. DR EMBL; BC008740; AAH08740.1; -; mRNA. DR EMBL; BC030574; AAH30574.1; -; mRNA. DR CCDS; CCDS12933.1; -. [P26368-1] DR CCDS; CCDS46197.1; -. [P26368-2] DR PIR; S20250; S20250. DR RefSeq; NP_001012496.1; NM_001012478.1. [P26368-2] DR RefSeq; NP_009210.1; NM_007279.2. [P26368-1] DR UniGene; Hs.528007; -. DR PDB; 1JMT; X-ray; 2.20 A; B=85-112. DR PDB; 1O0P; NMR; -; A=372-475. DR PDB; 1OPI; NMR; -; A=372-475. DR PDB; 1U2F; NMR; -; A=148-237. DR PDB; 2G4B; X-ray; 2.50 A; A=148-336. DR PDB; 2HZC; X-ray; 1.47 A; A=148-229. DR PDB; 2M0G; NMR; -; B=372-475. DR PDB; 2U2F; NMR; -; A=258-342. DR PDB; 2YH0; NMR; -; A=148-342. DR PDB; 2YH1; NMR; -; A=148-342. DR PDB; 3VAF; X-ray; 2.49 A; A/B=148-336. DR PDB; 3VAG; X-ray; 2.19 A; A/B=148-336. DR PDB; 3VAH; X-ray; 2.50 A; A/B=148-336. DR PDB; 3VAI; X-ray; 2.20 A; A/B=148-336. DR PDB; 3VAJ; X-ray; 1.90 A; A/B=148-336. DR PDB; 3VAK; X-ray; 2.17 A; A/B=148-336. DR PDB; 3VAL; X-ray; 2.50 A; A/B/D/I=148-336. DR PDB; 3VAM; X-ray; 2.40 A; A/B=148-336. DR PDB; 4FXW; X-ray; 2.29 A; A/C=375-475. DR PDB; 4TU7; X-ray; 2.09 A; A/B=148-336. DR PDB; 4TU8; X-ray; 1.92 A; A/B=148-336. DR PDB; 4TU9; X-ray; 1.99 A; A/B=148-336. DR PDB; 5EV1; X-ray; 2.04 A; A=141-341. DR PDB; 5EV2; X-ray; 1.86 A; A=141-341. DR PDB; 5EV3; X-ray; 1.50 A; A=141-341. DR PDB; 5EV4; X-ray; 1.57 A; A=141-341. DR PDB; 5W0G; X-ray; 1.07 A; A=148-229. DR PDB; 5W0H; X-ray; 1.11 A; A=258-336. DR PDBsum; 1JMT; -. DR PDBsum; 1O0P; -. DR PDBsum; 1OPI; -. DR PDBsum; 1U2F; -. DR PDBsum; 2G4B; -. DR PDBsum; 2HZC; -. DR PDBsum; 2M0G; -. DR PDBsum; 2U2F; -. DR PDBsum; 2YH0; -. DR PDBsum; 2YH1; -. DR PDBsum; 3VAF; -. DR PDBsum; 3VAG; -. DR PDBsum; 3VAH; -. DR PDBsum; 3VAI; -. DR PDBsum; 3VAJ; -. DR PDBsum; 3VAK; -. DR PDBsum; 3VAL; -. DR PDBsum; 3VAM; -. DR PDBsum; 4FXW; -. DR PDBsum; 4TU7; -. DR PDBsum; 4TU8; -. DR PDBsum; 4TU9; -. DR PDBsum; 5EV1; -. DR PDBsum; 5EV2; -. DR PDBsum; 5EV3; -. DR PDBsum; 5EV4; -. DR PDBsum; 5W0G; -. DR PDBsum; 5W0H; -. DR ProteinModelPortal; P26368; -. DR SMR; P26368; -. DR BioGrid; 116466; 381. DR CORUM; P26368; -. DR DIP; DIP-2154N; -. DR IntAct; P26368; 80. DR MINT; P26368; -. DR STRING; 9606.ENSP00000307863; -. DR iPTMnet; P26368; -. DR PhosphoSitePlus; P26368; -. DR SwissPalm; P26368; -. DR BioMuta; U2AF2; -. DR DMDM; 267188; -. DR EPD; P26368; -. DR MaxQB; P26368; -. DR PaxDb; P26368; -. DR PeptideAtlas; P26368; -. DR PRIDE; P26368; -. DR ProteomicsDB; 54325; -. DR ProteomicsDB; 54326; -. [P26368-2] DR TopDownProteomics; P26368-1; -. [P26368-1] DR TopDownProteomics; P26368-2; -. [P26368-2] DR DNASU; 11338; -. DR Ensembl; ENST00000308924; ENSP00000307863; ENSG00000063244. [P26368-1] DR Ensembl; ENST00000450554; ENSP00000388475; ENSG00000063244. [P26368-2] DR GeneID; 11338; -. DR KEGG; hsa:11338; -. DR UCSC; uc002qlt.4; human. [P26368-1] DR CTD; 11338; -. DR DisGeNET; 11338; -. DR EuPathDB; HostDB:ENSG00000063244.12; -. DR GeneCards; U2AF2; -. DR HGNC; HGNC:23156; U2AF2. DR HPA; CAB010910; -. DR HPA; HPA041943; -. DR HPA; HPA043562; -. DR MIM; 191318; gene. DR neXtProt; NX_P26368; -. DR OpenTargets; ENSG00000063244; -. DR PharmGKB; PA134908683; -. DR eggNOG; KOG0120; Eukaryota. DR eggNOG; ENOG410XP92; LUCA. DR GeneTree; ENSGT00940000155556; -. DR HOGENOM; HOG000180745; -. DR HOVERGEN; HBG062169; -. DR InParanoid; P26368; -. DR KO; K12837; -. DR OMA; MQAKQTG; -. DR OrthoDB; EOG091G08BA; -. DR PhylomeDB; P26368; -. DR TreeFam; TF314111; -. DR Reactome; R-HSA-109688; Cleavage of Growing Transcript in the Termination Region. 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 SIGNOR; P26368; -. DR ChiTaRS; U2AF2; human. DR EvolutionaryTrace; P26368; -. DR GeneWiki; U2AF2; -. DR GenomeRNAi; 11338; -. DR PMAP-CutDB; P26368; -. DR PRO; PR:P26368; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000063244; Expressed in 222 organ(s), highest expression level in right testis. DR CleanEx; HS_U2AF2; -. DR ExpressionAtlas; P26368; baseline and differential. DR Genevisible; P26368; HS. DR GO; GO:0000243; C:commitment complex; IBA:GO_Central. DR GO; GO:0016607; C:nuclear speck; IDA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:GO_Central. DR GO; GO:0005681; C:spliceosomal complex; IDA:HGNC. DR GO; GO:0071004; C:U2-type prespliceosome; IDA:GO_Central. DR GO; GO:0089701; C:U2AF; IDA:GO_Central. DR GO; GO:0070742; F:C2H2 zinc finger domain binding; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0008187; F:poly-pyrimidine tract binding; IBA:GO_Central. DR GO; GO:0030628; F:pre-mRNA 3'-splice site binding; IDA:GO_Central. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome. DR GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome. DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc. DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:GO_Central. DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:BHF-UCL. DR GO; GO:0033120; P:positive regulation of RNA splicing; IDA:UniProtKB. DR GO; GO:0006405; P:RNA export from nucleus; TAS:Reactome. DR Gene3D; 3.30.70.330; -; 3. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR InterPro; IPR006529; U2AF_lg. DR Pfam; PF00076; RRM_1; 3. DR SMART; SM00360; RRM; 3. DR SUPFAM; SSF54928; SSF54928; 3. DR TIGRFAMs; TIGR01642; U2AF_lg; 1. DR PROSITE; PS50102; RRM; 3. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Direct protein sequencing; Hydroxylation; Isopeptide bond; KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; RNA-binding; Spliceosome; KW Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000269|Ref.4}. FT CHAIN 2 475 Splicing factor U2AF 65 kDa subunit. FT /FTId=PRO_0000081988. FT DOMAIN 149 231 RRM 1. {ECO:0000255|PROSITE- FT ProRule:PRU00176}. FT DOMAIN 259 337 RRM 2. {ECO:0000255|PROSITE- FT ProRule:PRU00176}. FT DOMAIN 385 466 RRM 3. {ECO:0000255|PROSITE- FT ProRule:PRU00176}. FT REGION 2 93 Required for interaction with PRPF19. FT {ECO:0000269|PubMed:21536736}. FT REGION 17 47 Necessary and sufficient to stimulate FT pre-mRNAs 3'-end cleavage in a CFIm FT complex-dependent manner. FT {ECO:0000269|PubMed:17024186}. FT COMPBIAS 27 62 Arg/Ser-rich (RS domain). FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000269|Ref.4}. FT MOD_RES 2 2 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 15 15 5-hydroxylysine; by JMJD6; alternate. FT {ECO:0000269|PubMed:19574390}. FT MOD_RES 70 70 N6-acetyllysine; alternate. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 79 79 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 276 276 5-hydroxylysine; by JMJD6. FT {ECO:0000269|PubMed:19574390}. FT MOD_RES 294 294 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT CROSSLNK 15 15 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:28112733}. FT CROSSLNK 70 70 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447, FT ECO:0000244|PubMed:28112733}. FT VAR_SEQ 345 348 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035414. FT MUTAGEN 92 92 W->A: Decreases affinity for UAF1 by 3 FT orders of magnitude. FT {ECO:0000269|PubMed:11551507}. FT MUTAGEN 96 96 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT {ECO:0000269|PubMed:11551507}. FT MUTAGEN 104 104 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT {ECO:0000269|PubMed:11551507}. FT MUTAGEN 387 388 EE->RR: Reduces interaction with SF1. FT {ECO:0000269|PubMed:12718882}. FT MUTAGEN 391 394 DDEE->AAAA: Reduces interaction with SF1. FT MUTAGEN 391 394 DDEE->RRKK: Reduces interaction with SF1. FT MUTAGEN 396 397 EE->AA: No effect. FT {ECO:0000269|PubMed:12718882}. FT MUTAGEN 396 397 EE->GA: Reduces interaction with SF1. FT {ECO:0000269|PubMed:12718882}. FT MUTAGEN 396 397 EE->KK: Reduces interaction with SF1. FT {ECO:0000269|PubMed:12718882}. FT MUTAGEN 454 454 F->A: Reduces interaction with SF1. FT {ECO:0000269|PubMed:12718882}. FT HELIX 104 109 {ECO:0000244|PDB:1JMT}. FT HELIX 147 149 {ECO:0000244|PDB:5EV3}. FT STRAND 150 155 {ECO:0000244|PDB:5W0G}. FT HELIX 162 175 {ECO:0000244|PDB:5W0G}. FT STRAND 180 183 {ECO:0000244|PDB:5W0G}. FT STRAND 185 191 {ECO:0000244|PDB:5W0G}. FT TURN 193 196 {ECO:0000244|PDB:5EV3}. FT STRAND 197 203 {ECO:0000244|PDB:5W0G}. FT HELIX 205 211 {ECO:0000244|PDB:5W0G}. FT HELIX 212 214 {ECO:0000244|PDB:5W0G}. FT STRAND 219 222 {ECO:0000244|PDB:1U2F}. FT STRAND 225 227 {ECO:0000244|PDB:5W0G}. FT STRAND 238 240 {ECO:0000244|PDB:2YH0}. FT STRAND 244 246 {ECO:0000244|PDB:2YH1}. FT STRAND 260 264 {ECO:0000244|PDB:5W0H}. FT HELIX 272 280 {ECO:0000244|PDB:5W0H}. FT STRAND 281 283 {ECO:0000244|PDB:2U2F}. FT STRAND 285 292 {ECO:0000244|PDB:5W0H}. FT TURN 294 296 {ECO:0000244|PDB:5W0H}. FT STRAND 299 308 {ECO:0000244|PDB:5W0H}. FT HELIX 310 320 {ECO:0000244|PDB:5W0H}. FT STRAND 326 328 {ECO:0000244|PDB:2U2F}. FT STRAND 331 334 {ECO:0000244|PDB:5W0H}. FT HELIX 335 338 {ECO:0000244|PDB:5EV3}. FT STRAND 376 383 {ECO:0000244|PDB:4FXW}. FT HELIX 386 389 {ECO:0000244|PDB:4FXW}. FT HELIX 392 406 {ECO:0000244|PDB:4FXW}. FT TURN 407 409 {ECO:0000244|PDB:1O0P}. FT STRAND 414 416 {ECO:0000244|PDB:4FXW}. FT TURN 422 424 {ECO:0000244|PDB:4FXW}. FT TURN 427 430 {ECO:0000244|PDB:4FXW}. FT STRAND 431 435 {ECO:0000244|PDB:4FXW}. FT HELIX 439 449 {ECO:0000244|PDB:4FXW}. FT STRAND 454 457 {ECO:0000244|PDB:1O0P}. FT STRAND 460 463 {ECO:0000244|PDB:4FXW}. FT HELIX 466 470 {ECO:0000244|PDB:4FXW}. SQ SEQUENCE 475 AA; 53501 MW; 26AD271CD8FC6211 CRC64; MSDFDEFERQ LNENKQERDK ENRHRKRSHS RSRSRDRKRR SRSRDRRNRD QRSASRDRRR RSKPLTRGAK EEHGGLIRSP RHEKKKKVRK YWDVPPPGFE HITPMQYKAM QAAGQIPATA LLPTMTPDGL AVTPTPVPVV GSQMTRQARR LYVGNIPFGI TEEAMMDFFN AQMRLGGLTQ APGNPVLAVQ INQDKNFAFL EFRSVDETTQ AMAFDGIIFQ GQSLKIRRPH DYQPLPGMSE NPSVYVPGVV STVVPDSAHK LFIGGLPNYL NDDQVKELLT SFGPLKAFNL VKDSATGLSK GYAFCEYVDI NVTDQAIAGL NGMQLGDKKL LVQRASVGAK NATLVSPPST INQTPVTLQV PGLMSSQVQM GGHPTEVLCL MNMVLPEELL DDEEYEEIVE DVRDECSKYG LVKSIEIPRP VDGVEVPGCG KIFVEFTSVF DCQKAMQGLT GRKFANRVVV TKYCDPDSYH RRDFW //