U2AF2_HUMAN
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 03-AUG-2022, entry version 233.
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}.
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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 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 AlphaFoldDB; P26368; -.
DR BMRB; P26368; -.
DR SMR; P26368; -.
DR BioGRID; 116466; 491.
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; 140.
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; P26368; -.
DR PeptideAtlas; P26368; -.
DR PRIDE; P26368; -.
DR ProteomicsDB; 54325; -. [P26368-1]
DR ProteomicsDB; 54326; -. [P26368-2]
DR TopDownProteomics; P26368-1; -. [P26368-1]
DR TopDownProteomics; P26368-2; -. [P26368-2]
DR Antibodypedia; 4399; 277 antibodies from 27 providers.
DR DNASU; 11338; -.
DR Ensembl; ENST00000308924.9; ENSP00000307863.3; ENSG00000063244.13. [P26368-1]
DR Ensembl; ENST00000450554.6; ENSP00000388475.1; ENSG00000063244.13. [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 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; 896650at2759; -.
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 SignaLink; P26368; -.
DR SIGNOR; P26368; -.
DR BioGRID-ORCS; 11338; 796 hits in 1092 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 198 other tissues.
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-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: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 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 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; 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:5EV3"
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 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:4FXW"
FT HELIX 386..389
FT /evidence="ECO:0007829|PDB:4FXW"
FT HELIX 392..406
FT /evidence="ECO:0007829|PDB:4FXW"
FT TURN 407..409
FT /evidence="ECO:0007829|PDB:1O0P"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:4FXW"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:4FXW"
FT TURN 427..430
FT /evidence="ECO:0007829|PDB:4FXW"
FT STRAND 431..435
FT /evidence="ECO:0007829|PDB:4FXW"
FT HELIX 439..449
FT /evidence="ECO:0007829|PDB:4FXW"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:1O0P"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:4FXW"
FT HELIX 466..470
FT /evidence="ECO:0007829|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
