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 27-MAR-2024, entry version 242. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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 U2AF65 and RT 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 protein RT 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., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT 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 factors."; RL J. Neurochem. 88:1078-1090(2004). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS RP 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., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT 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' end RT 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., Valcarcel J., RA Sattler M.; RT "U2AF-homology motif interactions are required for alternative splicing RT 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 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 [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., Grillari-Voglauer R.; RT "Blom7alpha is a novel heterogeneous nuclear ribonucleoprotein K homology RT domain protein involved in pre-mRNA splicing that interacts with SNEVPrp19- RT 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 to RT 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 MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA 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 with RT RNA splicing."; RL Science 325:90-93(2009). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-2 AND SER-79, CLEAVAGE OF INITIATOR METHIONINE [LARGE RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [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., 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 [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 MASS RP 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 [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA 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 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 [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-79 AND SER-294, 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, AND IDENTIFICATION BY RP 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 [30] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-70, AND IDENTIFICATION BY MASS RP 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., Pena V.; RT "Molecular architecture of SF3b and structural consequences of its cancer- RT related mutations."; RL Mol. Cell 64:307-319(2016). RN [32] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-15 AND LYS-70, AND IDENTIFICATION RP 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-modification RT 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 human RT U2 small nuclear ribonucleoprotein particle auxiliary factor (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., Kraemer A., RA 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, AND RP 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 core RT 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 domain CC (CTD), and thereby pre-mRNA, may couple transcription to splicing CC (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon CC inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through CC competition with MBNL1. Binds preferentially to a single-stranded CC structure within the polypyrimidine tract of TNNT2 intron 4 during CC spliceosome assembly. Required for the export of mRNA out of the CC nucleus, even if the mRNA is encoded by an intron-less gene. Represses CC the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end CC processing by recruiting the CFIm complex to cleavage and CC polyadenylation signals (PubMed:17024186). CC {ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:17024186, CC ECO:0000269|PubMed:19470458, ECO:0000269|PubMed:19574390, CC ECO:0000269|PubMed:21536736}. CC -!- SUBUNIT: Interacts with U2AF1L4 (By similarity). Heterodimer with U2AF1 CC (PubMed:11551507). Binds unphosphorylated SF1 (PubMed:10449420, CC PubMed:12718882). Interacts with SCAF11 and SNW1 (PubMed:9447963, CC PubMed:21460037). Interacts with ZRSR2/U2AF1-RS2. Interacts with RBM17 CC (PubMed:17589525). Interacts with PRPF19; the interaction is direct. CC Interacts with POLR2A (via the C-terminal domain); recruits PRPF19 and CC the Prp19 complex to the pre-mRNA (PubMed:21536736). Interacts with CC KHDC4 (Isoform 2) (PubMed:19641227). Interacts with ZRSR2 CC (PubMed:9237760). Interacts with the SF3B complex composed of SF3B1, CC SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A (PubMed:27720643). CC Interacts (via N-terminus) with CPSF7 (via C-terminus); this CC interaction stimulates pre-mRNA 3'-end processing by promoting the CC recruitment of the 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 P26368; P54253: ATXN1; NbExp=5; IntAct=EBI-742339, EBI-930964; CC P26368; Q8IWX8: CHERP; NbExp=2; IntAct=EBI-742339, EBI-2555370; CC P26368; Q8N684: CPSF7; NbExp=2; IntAct=EBI-742339, EBI-746909; CC P26368; Q9UI36-2: DACH1; NbExp=3; IntAct=EBI-742339, EBI-10186082; CC P26368; O43395: PRPF3; NbExp=2; IntAct=EBI-742339, EBI-744322; CC P26368; Q9UHX1: PUF60; NbExp=5; IntAct=EBI-742339, EBI-1053259; CC P26368; P98175: RBM10; NbExp=2; IntAct=EBI-742339, EBI-721525; CC P26368; Q96I25: RBM17; NbExp=2; IntAct=EBI-742339, EBI-740272; CC P26368; P52756: RBM5; NbExp=2; IntAct=EBI-742339, EBI-714003; CC P26368; P82979: SARNP; NbExp=3; IntAct=EBI-742339, EBI-347495; CC P26368; Q15637: SF1; NbExp=22; IntAct=EBI-742339, EBI-744603; CC P26368; P09012: SNRPA; NbExp=5; IntAct=EBI-742339, EBI-607085; CC P26368; Q13573: SNW1; NbExp=5; IntAct=EBI-742339, EBI-632715; CC P26368; P78362: SRPK2; NbExp=5; IntAct=EBI-742339, EBI-593303; CC P26368; Q8IWZ8: SUGP1; NbExp=3; IntAct=EBI-742339, EBI-2691671; CC P26368; Q9NVV9: THAP1; NbExp=4; IntAct=EBI-742339, EBI-741515; CC P26368; Q08117: TLE5; NbExp=3; IntAct=EBI-742339, EBI-717810; CC P26368; Q01081: U2AF1; NbExp=11; IntAct=EBI-742339, EBI-632461; CC P26368-2; Q13838: DDX39B; NbExp=3; IntAct=EBI-11097439, EBI-348622; CC P26368-2; Q96AE4-2: FUBP1; NbExp=3; IntAct=EBI-11097439, EBI-12121668; CC P26368-2; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-11097439, EBI-2549423; CC P26368-2; Q9C086: INO80B; NbExp=3; IntAct=EBI-11097439, EBI-715611; CC P26368-2; Q7Z7F0-4: KHDC4; NbExp=3; IntAct=EBI-11097439, EBI-9089060; CC P26368-2; Q9P015: MRPL15; NbExp=3; IntAct=EBI-11097439, EBI-2371967; CC P26368-2; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-11097439, EBI-3920396; CC P26368-2; O43395: PRPF3; NbExp=3; IntAct=EBI-11097439, EBI-744322; CC P26368-2; Q9UHX1-2: PUF60; NbExp=3; IntAct=EBI-11097439, EBI-11529177; CC P26368-2; P57052: RBM11; NbExp=3; IntAct=EBI-11097439, EBI-741332; CC P26368-2; Q15415: RBMY1J; NbExp=3; IntAct=EBI-11097439, EBI-8642021; CC P26368-2; Q15637-4: SF1; NbExp=5; IntAct=EBI-11097439, EBI-12223157; CC P26368-2; P09012: SNRPA; NbExp=6; IntAct=EBI-11097439, EBI-607085; CC P26368-2; P78362: SRPK2; NbExp=3; IntAct=EBI-11097439, EBI-593303; CC P26368-2; P84103: SRSF3; NbExp=3; IntAct=EBI-11097439, EBI-372557; CC P26368-2; Q96MF2: STAC3; NbExp=3; IntAct=EBI-11097439, EBI-745680; CC P26368-2; Q7RTU1: TCF23; NbExp=3; IntAct=EBI-11097439, EBI-12127592; CC P26368-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11097439, EBI-11741437; CC P26368-2; Q01081: U2AF1; NbExp=8; IntAct=EBI-11097439, EBI-632461; CC P26368-2; Q9UII5: ZNF107; NbExp=3; IntAct=EBI-11097439, EBI-7234993; CC P26368-2; Q8TF50: ZNF526; NbExp=3; IntAct=EBI-11097439, EBI-11035148; CC P26368-2; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-11097439, EBI-8490788; CC P26368-2; Q9NQZ8: ZNF71; NbExp=3; IntAct=EBI-11097439, EBI-7138235; CC P26368-2; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-11097439, EBI-5667516; CC P26368-2; Q15695: ZRSR2P1; NbExp=3; IntAct=EBI-11097439, EBI-12270264; 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 not CC all, alternative splicing events. {ECO:0000269|PubMed:19574390}. CC -!- SIMILARITY: Belongs to the splicing factor SR family. {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 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 PDB; 6TR0; NMR; -; A=140-342. DR PDB; 6XLV; X-ray; 1.40 A; A=141-341. DR PDB; 6XLW; X-ray; 1.50 A; A=141-341. DR PDB; 6XLX; X-ray; 1.70 A; A=141-341. DR PDB; 7S3A; X-ray; 1.48 A; A=141-341. DR PDB; 7S3B; X-ray; 1.89 A; A=141-341. DR PDB; 7S3C; X-ray; 1.51 A; A=141-341. DR PDB; 7SN6; X-ray; 1.80 A; A/B=375-475. DR PDB; 8P25; NMR; -; A=231-342. 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 PDBsum; 6TR0; -. DR PDBsum; 6XLV; -. DR PDBsum; 6XLW; -. DR PDBsum; 6XLX; -. DR PDBsum; 7S3A; -. DR PDBsum; 7S3B; -. DR PDBsum; 7S3C; -. DR PDBsum; 7SN6; -. DR PDBsum; 8P25; -. DR AlphaFoldDB; P26368; -. DR BMRB; P26368; -. DR SMR; P26368; -. DR BioGRID; 116466; 625. DR ComplexPortal; CPX-1074; SF1-U2AF65 splicing factor complex. DR ComplexPortal; CPX-1921; U2 small nuclear ribonucleoprotein auxiliary factor complex. DR CORUM; P26368; -. DR DIP; DIP-2154N; -. DR IntAct; P26368; 146. DR MINT; P26368; -. DR STRING; 9606.ENSP00000307863; -. DR GlyGen; P26368; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P26368; -. DR PhosphoSitePlus; P26368; -. DR SwissPalm; P26368; -. DR BioMuta; U2AF2; -. DR DMDM; 267188; -. DR EPD; P26368; -. DR jPOST; P26368; -. DR MassIVE; P26368; -. DR MaxQB; P26368; -. DR PaxDb; 9606-ENSP00000307863; -. DR PeptideAtlas; P26368; -. DR ProteomicsDB; 54325; -. [P26368-1] DR ProteomicsDB; 54326; -. [P26368-2] DR Pumba; P26368; -. DR TopDownProteomics; P26368-1; -. [P26368-1] DR TopDownProteomics; P26368-2; -. [P26368-2] DR Antibodypedia; 4399; 299 antibodies from 27 providers. DR DNASU; 11338; -. DR Ensembl; ENST00000308924.9; ENSP00000307863.3; ENSG00000063244.14. [P26368-1] DR Ensembl; ENST00000450554.6; ENSP00000388475.1; ENSG00000063244.14. [P26368-2] DR GeneID; 11338; -. DR KEGG; hsa:11338; -. DR MANE-Select; ENST00000308924.9; ENSP00000307863.3; NM_007279.3; NP_009210.1. DR UCSC; uc002qlt.4; human. [P26368-1] DR AGR; HGNC:23156; -. DR CTD; 11338; -. DR DisGeNET; 11338; -. DR GeneCards; U2AF2; -. DR HGNC; HGNC:23156; U2AF2. DR HPA; ENSG00000063244; Low tissue specificity. DR MIM; 191318; gene. DR neXtProt; NX_P26368; -. DR OpenTargets; ENSG00000063244; -. DR PharmGKB; PA134908683; -. DR VEuPathDB; HostDB:ENSG00000063244; -. DR eggNOG; KOG0120; Eukaryota. DR GeneTree; ENSGT00940000155556; -. DR InParanoid; P26368; -. DR OMA; MTQWDIK; -. DR OrthoDB; 101932at2759; -. DR PhylomeDB; P26368; -. DR TreeFam; TF314111; -. DR PathwayCommons; P26368; -. 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 Reactome; R-HSA-9629569; Protein hydroxylation. DR SignaLink; P26368; -. DR SIGNOR; P26368; -. DR BioGRID-ORCS; 11338; 834 hits in 1173 CRISPR screens. DR ChiTaRS; U2AF2; human. DR EvolutionaryTrace; P26368; -. DR GeneWiki; U2AF2; -. DR GenomeRNAi; 11338; -. DR Pharos; P26368; Tbio. DR PRO; PR:P26368; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P26368; Protein. DR Bgee; ENSG00000063244; Expressed in right uterine tube and 200 other cell types or tissues. DR ExpressionAtlas; P26368; baseline and differential. DR GO; GO:0000243; C:commitment complex; IBA:GO_Central. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. 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-UCL. DR GO; GO:0071004; C:U2-type prespliceosome; IDA:GO_Central. DR GO; GO:0089701; C:U2AF complex; 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:0140678; F:molecular function inhibitor activity; EXP:DisProt. 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: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 CDD; cd12230; RRM1_U2AF65; 1. DR CDD; cd12231; RRM2_U2AF65; 1. DR CDD; cd12232; RRM3_U2AF65; 1. DR DisProt; DP02921; -. DR Gene3D; 3.30.70.330; -; 3. DR IDEAL; IID00147; -. 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 NCBIfam; TIGR01642; U2AF_lg; 1. DR PANTHER; PTHR23139; RNA-BINDING PROTEIN; 1. DR PANTHER; PTHR23139:SF9; SPLICING FACTOR U2AF 65 KDA SUBUNIT; 1. DR Pfam; PF00076; RRM_1; 3. DR SMART; SM00360; RRM; 3. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 3. DR PROSITE; PS50102; RRM; 3. DR Genevisible; P26368; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Hydroxylation; Isopeptide bond; mRNA processing; mRNA splicing; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Repressor; RNA-binding; KW Spliceosome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..475 FT /note="Splicing factor U2AF 65 kDa subunit" FT /id="PRO_0000081988" FT DOMAIN 149..231 FT /note="RRM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 259..337 FT /note="RRM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 385..466 FT /note="RRM 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT REGION 1..90 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..93 FT /note="Required for interaction with PRPF19" FT /evidence="ECO:0000269|PubMed:21536736" FT REGION 17..47 FT /note="Necessary and sufficient to stimulate pre-mRNAs 3'- FT end cleavage in a CFIm complex-dependent manner" FT /evidence="ECO:0000269|PubMed:17024186" FT COMPBIAS 1..23 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 24..46 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 64..79 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 15 FT /note="5-hydroxylysine; by JMJD6; alternate" FT /evidence="ECO:0000269|PubMed:19574390" FT MOD_RES 70 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 79 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 276 FT /note="5-hydroxylysine; by JMJD6" FT /evidence="ECO:0000269|PubMed:19574390" FT MOD_RES 294 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 15 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 70 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 345..348 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_035414" FT MUTAGEN 92 FT /note="W->A: Decreases affinity for UAF1 by 3 orders of FT magnitude." FT /evidence="ECO:0000269|PubMed:11551507" FT MUTAGEN 96 FT /note="P->G: Decreases affinity for UAF1 by 2 orders of FT magnitude." FT /evidence="ECO:0000269|PubMed:11551507" FT MUTAGEN 104 FT /note="P->G: Decreases affinity for UAF1 by 2 orders of FT magnitude." FT /evidence="ECO:0000269|PubMed:11551507" FT MUTAGEN 387..388 FT /note="EE->RR: Reduces interaction with SF1." FT /evidence="ECO:0000269|PubMed:12718882" FT MUTAGEN 391..394 FT /note="DDEE->AAAA: Reduces interaction with SF1." FT MUTAGEN 391..394 FT /note="DDEE->RRKK: Reduces interaction with SF1." FT MUTAGEN 396..397 FT /note="EE->AA: No effect." FT /evidence="ECO:0000269|PubMed:12718882" FT MUTAGEN 396..397 FT /note="EE->GA: Reduces interaction with SF1." FT /evidence="ECO:0000269|PubMed:12718882" FT MUTAGEN 396..397 FT /note="EE->KK: Reduces interaction with SF1." FT /evidence="ECO:0000269|PubMed:12718882" FT MUTAGEN 454 FT /note="F->A: Reduces interaction with SF1." FT /evidence="ECO:0000269|PubMed:12718882" FT HELIX 104..109 FT /evidence="ECO:0007829|PDB:1JMT" FT HELIX 143..149 FT /evidence="ECO:0007829|PDB:6XLV" FT STRAND 150..155 FT /evidence="ECO:0007829|PDB:5W0G" FT HELIX 162..175 FT /evidence="ECO:0007829|PDB:5W0G" FT STRAND 180..183 FT /evidence="ECO:0007829|PDB:5W0G" FT STRAND 185..191 FT /evidence="ECO:0007829|PDB:5W0G" FT TURN 193..196 FT /evidence="ECO:0007829|PDB:7S3A" FT STRAND 197..203 FT /evidence="ECO:0007829|PDB:5W0G" FT HELIX 205..211 FT /evidence="ECO:0007829|PDB:5W0G" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:5W0G" FT STRAND 219..222 FT /evidence="ECO:0007829|PDB:1U2F" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:5W0G" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:2YH0" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:2YH1" FT STRAND 250..253 FT /evidence="ECO:0007829|PDB:8P25" FT STRAND 260..264 FT /evidence="ECO:0007829|PDB:5W0H" FT HELIX 272..280 FT /evidence="ECO:0007829|PDB:5W0H" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:2U2F" FT STRAND 285..292 FT /evidence="ECO:0007829|PDB:5W0H" FT TURN 294..296 FT /evidence="ECO:0007829|PDB:5W0H" FT STRAND 299..308 FT /evidence="ECO:0007829|PDB:5W0H" FT HELIX 310..320 FT /evidence="ECO:0007829|PDB:5W0H" FT STRAND 323..325 FT /evidence="ECO:0007829|PDB:6TR0" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:2U2F" FT STRAND 331..334 FT /evidence="ECO:0007829|PDB:5W0H" FT HELIX 335..338 FT /evidence="ECO:0007829|PDB:6XLV" FT STRAND 376..383 FT /evidence="ECO:0007829|PDB:7SN6" FT HELIX 386..389 FT /evidence="ECO:0007829|PDB:7SN6" FT HELIX 392..406 FT /evidence="ECO:0007829|PDB:7SN6" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:7SN6" FT STRAND 412..416 FT /evidence="ECO:0007829|PDB:7SN6" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:4FXW" FT TURN 427..430 FT /evidence="ECO:0007829|PDB:7SN6" FT STRAND 432..438 FT /evidence="ECO:0007829|PDB:7SN6" FT HELIX 439..449 FT /evidence="ECO:0007829|PDB:7SN6" FT STRAND 454..457 FT /evidence="ECO:0007829|PDB:1O0P" FT STRAND 460..464 FT /evidence="ECO:0007829|PDB:7SN6" FT HELIX 466..471 FT /evidence="ECO:0007829|PDB:7SN6" 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 //