SRSF2_HUMAN
ID SRSF2_HUMAN Reviewed; 221 AA.
AC Q01130; B3KWD5; B4DN89; H0YG49;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 243.
DE RecName: Full=Serine/arginine-rich splicing factor 2;
DE AltName: Full=Protein PR264;
DE AltName: Full=Splicing component, 35 kDa;
DE AltName: Full=Splicing factor SC35;
DE Short=SC-35;
DE AltName: Full=Splicing factor, arginine/serine-rich 2;
GN Name=SRSF2; Synonyms=SFRS2;
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), AND PROTEIN SEQUENCE OF 67-84.
RX PubMed=1373910; DOI=10.1126/science.1373910;
RA Fu X.-D., Maniatis T.;
RT "Isolation of a complementary DNA that encodes the mammalian splicing
RT factor SC35.";
RL Science 256:535-538(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=1557353; DOI=10.1073/pnas.89.7.2511;
RA Vellard M., Sureau A., Soret J., Martinerie C., Perbal B.;
RT "A potential splicing factor is encoded by the opposite strand of the
RT trans-spliced c-myb exon.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2511-2515(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8302870; DOI=10.1073/pnas.91.3.932;
RA Sureau A., Perbal B.;
RT "Several mRNAs with variable 3' untranslated regions and different
RT stability encode the human PR264/SC35 splicing factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:932-936(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Placenta, and Testis;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-34.
RX PubMed=1465383; DOI=10.1073/pnas.89.24.11683;
RA Sureau A., Soret J., Vellard M., Crochet J., Perbal B.;
RT "The PR264/c-myb connection: expression of a splicing factor modulated by a
RT nuclear protooncogene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11683-11687(1992).
RN [10]
RP PROTEIN SEQUENCE OF 2-17, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUL-2004) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 67-83.
RX PubMed=1577277; DOI=10.1101/gad.6.5.837;
RA Zahler A.M., Lane W.S., Stolk J.A., Roth M.B.;
RT "SR proteins: a conserved family of pre-mRNA splicing factors.";
RL Genes Dev. 6:837-847(1992).
RN [12]
RP INTERACTION IN SPLICEOSOME ASSEMBLY.
RX PubMed=8261509; DOI=10.1016/0092-8674(93)90316-i;
RA Wu J.Y., Maniatis T.;
RT "Specific interactions between proteins implicated in splice site selection
RT and regulated alternative splicing.";
RL Cell 75:1061-1070(1993).
RN [13]
RP SPECIFICITY FOR BETA-GLOBIN MRNA.
RX PubMed=8361546; DOI=10.1038/365082a0;
RA Fu X.-D.;
RT "Specific commitment of different pre-mRNAs to splicing by single SR
RT proteins.";
RL Nature 365:82-85(1993).
RN [14]
RP INTERACTION WITH U1-70K.
RX PubMed=8139654; DOI=10.1038/368119a0;
RA Kohtz J.D., Jamison S.F., Will C.L., Zuo P., Luehrmann R.,
RA Garcia-Blanco M.A., Manley J.L.;
RT "Protein-protein interactions and 5'-splice-site recognition in mammalian
RT mRNA precursors.";
RL Nature 368:119-124(1994).
RN [15]
RP RNA-BINDING SPECIFICITY.
RX PubMed=7543047; DOI=10.1002/j.1460-2075.1995.tb07360.x;
RA Tacke R., Manley J.L.;
RT "The human splicing factors ASF/SF2 and SC35 possess distinct, functionally
RT significant RNA binding specificities.";
RL EMBO J. 14:3540-3551(1995).
RN [16]
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 [17]
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 [18]
RP INTERACTION WITH SREK1.
RX PubMed=10757789; DOI=10.1128/mcb.20.9.3049-3057.2000;
RA Barnard D.C., Patton J.G.;
RT "Identification and characterization of a novel serine-arginine-rich
RT splicing regulatory protein.";
RL Mol. Cell. Biol. 20:3049-3057(2000).
RN [19]
RP INTERACTION WITH CCNL1.
RX PubMed=11980906; DOI=10.1074/jbc.m202266200;
RA Dickinson L.A., Edgar A.J., Ehley J., Gottesfeld J.M.;
RT "Cyclin L is an RS domain protein involved in pre-mRNA splicing.";
RL J. Biol. Chem. 277:25465-25473(2002).
RN [20]
RP INTERACTION WITH CCNL2.
RX PubMed=14684736; DOI=10.1074/jbc.m312895200;
RA Yang L., Li N., Wang C., Yu Y., Yuan L., Zhang M., Cao X.;
RT "Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in
RT pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma
RT cells.";
RL J. Biol. Chem. 279:11639-11648(2004).
RN [21]
RP IDENTIFICATION BY 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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206 AND SER-208, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-204; SER-206; SER-208
RP AND SER-212, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [24]
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 [25]
RP FUNCTION, AND PHOSPHORYLATION BY SRPK2.
RX PubMed=19592491; DOI=10.1074/jbc.m109.026237;
RA Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.;
RT "Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle
RT and cell death in neurons.";
RL J. Biol. Chem. 284:24512-24525(2009).
RN [26]
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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2; THR-22; THR-25; SER-26; SER-208 AND SER-212, CLEAVAGE
RP OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
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 [29]
RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-52, AND PHOSPHORYLATION
RP BY SRPK2.
RX PubMed=21157427; DOI=10.1038/emboj.2010.333;
RA Edmond V., Moysan E., Khochbin S., Matthias P., Brambilla C., Brambilla E.,
RA Gazzeri S., Eymin B.;
RT "Acetylation and phosphorylation of SRSF2 control cell fate decision in
RT response to cisplatin.";
RL EMBO J. 30:510-523(2011).
RN [30]
RP INTERACTION WITH CCDC55.
RX PubMed=21296756; DOI=10.1093/nar/gkq1267;
RA Kim Y.D., Lee J.Y., Oh K.M., Araki M., Araki K., Yamamura K.I., Jun C.D.;
RT "NSrp70 is a novel nuclear speckle-related protein that modulates
RT alternative pre-mRNA splicing in vivo.";
RL Nucleic Acids Res. 39:4300-4314(2011).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2; THR-22; SER-189; SER-191; SER-208; SER-212 AND SER-220,
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-206 AND SER-208, 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 [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
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=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Necessary for the splicing of pre-mRNA. It is required for
CC formation of the earliest ATP-dependent splicing complex and interacts
CC with spliceosomal components bound to both the 5'- and 3'-splice sites
CC during spliceosome assembly. It also is required for ATP-dependent
CC interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with
CC other spliceosomal components, via the RS domains, to form a bridge
CC between the 5'- and 3'-splice site binding components, U1 snRNP and
CC U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C
CC or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to
CC the splicing pathway. The phosphorylated form (by SRPK2) is required
CC for cellular apoptosis in response to cisplatin treatment.
CC {ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21157427}.
CC -!- SUBUNIT: Interacts with BRDT (By similarity). In vitro, self-associates
CC and binds SRSF1/SFRS1 (ASF/SF2), SNRNP70 and U2AF1 but not U2AF2. Binds
CC SREK1/SFRS12. Interacts with CCNL1 and CCNL2. Interacts with SCAF11.
CC Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus).
CC {ECO:0000250, ECO:0000269|PubMed:10757789, ECO:0000269|PubMed:11980906,
CC ECO:0000269|PubMed:14684736, ECO:0000269|PubMed:21296756,
CC ECO:0000269|PubMed:8139654, ECO:0000269|PubMed:8261509,
CC ECO:0000269|PubMed:9237760, ECO:0000269|PubMed:9447963}.
CC -!- INTERACTION:
CC Q01130; Q86X95: CIR1; NbExp=4; IntAct=EBI-627047, EBI-627102;
CC Q01130; Q92993: KAT5; NbExp=3; IntAct=EBI-627047, EBI-399080;
CC Q01130; Q01081: U2AF1; NbExp=3; IntAct=EBI-627047, EBI-632461;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21157427}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:21157427}. Nucleus speckle
CC {ECO:0000269|PubMed:21157427}. Note=Phosphorylation by SRPK2 provokes
CC its redistribution from the nuclear speckle to nucleoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q01130-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q01130-2; Sequence=VSP_056153;
CC -!- INDUCTION: Accumulates in a hypoacetylated/phosphorylated form in
CC response to cisplatin treatment.
CC -!- PTM: Extensively phosphorylated on serine residues in the RS domain.
CC Phosphorylated by SRPK2 and this causes its redistribution from the
CC nuclear speckle to nucleoplasm and controls cell fate decision in
CC response to cisplatin treatment. KAT5/TIP60 inhibits its
CC phosphorylation by preventing SRPK2 nuclear translocation.
CC {ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21157427}.
CC -!- PTM: Acetylation on Lys-52 by KAT5/TIP60 promotes its proteasomal
CC degradation. This effect is counterbalanced by HDAC6, which positively
CC controls SRSF2 protein level by deacetylating it and preventing its
CC proteasomal degradation. {ECO:0000269|PubMed:21157427,
CC ECO:0000269|Ref.10}.
CC -!- SIMILARITY: Belongs to the splicing factor SR family. {ECO:0000305}.
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DR EMBL; M90104; AAA60306.1; -; mRNA.
DR EMBL; X62447; CAA44307.1; -; mRNA.
DR EMBL; X75755; CAA53383.1; -; Genomic_DNA.
DR EMBL; BT007250; AAP35914.1; -; mRNA.
DR EMBL; AK124792; BAG54097.1; -; mRNA.
DR EMBL; AK297813; BAG60151.1; -; mRNA.
DR EMBL; AC005837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89439.1; -; Genomic_DNA.
DR EMBL; CH471099; EAW89448.1; -; Genomic_DNA.
DR EMBL; BC000339; AAH00339.1; -; mRNA.
DR EMBL; BC001303; AAH01303.1; -; mRNA.
DR EMBL; BC070086; AAH70086.1; -; mRNA.
DR EMBL; L03693; AAA60162.1; -; Genomic_DNA.
DR CCDS; CCDS11749.1; -. [Q01130-1]
DR RefSeq; NP_001182356.1; NM_001195427.1. [Q01130-1]
DR RefSeq; NP_003007.2; NM_003016.4. [Q01130-1]
DR RefSeq; XP_016880431.1; XM_017024942.1. [Q01130-1]
DR PDB; 2KN4; NMR; -; A=9-101.
DR PDB; 2LEA; NMR; -; A=1-101.
DR PDB; 2LEB; NMR; -; A=1-101.
DR PDB; 2LEC; NMR; -; A=1-101.
DR PDBsum; 2KN4; -.
DR PDBsum; 2LEA; -.
DR PDBsum; 2LEB; -.
DR PDBsum; 2LEC; -.
DR AlphaFoldDB; Q01130; -.
DR BMRB; Q01130; -.
DR SMR; Q01130; -.
DR BioGRID; 112325; 194.
DR CORUM; Q01130; -.
DR DIP; DIP-33836N; -.
DR IntAct; Q01130; 80.
DR MINT; Q01130; -.
DR STRING; 9606.ENSP00000376276; -.
DR iPTMnet; Q01130; -.
DR MetOSite; Q01130; -.
DR PhosphoSitePlus; Q01130; -.
DR SwissPalm; Q01130; -.
DR BioMuta; SRSF2; -.
DR DMDM; 60416437; -.
DR EPD; Q01130; -.
DR jPOST; Q01130; -.
DR MassIVE; Q01130; -.
DR MaxQB; Q01130; -.
DR PaxDb; Q01130; -.
DR PeptideAtlas; Q01130; -.
DR PRIDE; Q01130; -.
DR ProteomicsDB; 38281; -.
DR ProteomicsDB; 57922; -. [Q01130-1]
DR TopDownProteomics; Q01130-1; -. [Q01130-1]
DR Antibodypedia; 19705; 143 antibodies from 27 providers.
DR DNASU; 6427; -.
DR Ensembl; ENST00000359995.10; ENSP00000353089.5; ENSG00000161547.17. [Q01130-1]
DR Ensembl; ENST00000392485.2; ENSP00000376276.2; ENSG00000161547.17. [Q01130-1]
DR Ensembl; ENST00000452355.7; ENSP00000391278.3; ENSG00000161547.17. [Q01130-1]
DR Ensembl; ENST00000508921.7; ENSP00000441780.2; ENSG00000161547.17. [Q01130-2]
DR Ensembl; ENST00000585202.5; ENSP00000462425.1; ENSG00000161547.17. [Q01130-1]
DR GeneID; 6427; -.
DR KEGG; hsa:6427; -.
DR MANE-Select; ENST00000359995.10; ENSP00000353089.5; NM_001195427.2; NP_001182356.1.
DR UCSC; uc002jsv.4; human. [Q01130-1]
DR CTD; 6427; -.
DR DisGeNET; 6427; -.
DR GeneCards; SRSF2; -.
DR HGNC; HGNC:10783; SRSF2.
DR HPA; ENSG00000161547; Low tissue specificity.
DR MalaCards; SRSF2; -.
DR MIM; 600813; gene.
DR neXtProt; NX_Q01130; -.
DR OpenTargets; ENSG00000161547; -.
DR Orphanet; 98850; Aggressive systemic mastocytosis.
DR Orphanet; 98823; Chronic myelomonocytic leukemia.
DR Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm.
DR PharmGKB; PA35699; -.
DR VEuPathDB; HostDB:ENSG00000161547; -.
DR eggNOG; KOG4207; Eukaryota.
DR GeneTree; ENSGT00940000154883; -.
DR HOGENOM; CLU_012062_10_3_1; -.
DR InParanoid; Q01130; -.
DR OMA; PLIRCDV; -.
DR PhylomeDB; Q01130; -.
DR TreeFam; TF106262; -.
DR PathwayCommons; Q01130; -.
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-72165; mRNA Splicing - Minor Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR SignaLink; Q01130; -.
DR SIGNOR; Q01130; -.
DR BioGRID-ORCS; 6427; 804 hits in 1090 CRISPR screens.
DR ChiTaRS; SRSF2; human.
DR EvolutionaryTrace; Q01130; -.
DR GeneWiki; SFRS2; -.
DR GenomeRNAi; 6427; -.
DR Pharos; Q01130; Tbio.
DR PRO; PR:Q01130; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q01130; protein.
DR Bgee; ENSG00000161547; Expressed in tibia and 214 other tissues.
DR ExpressionAtlas; Q01130; baseline and differential.
DR Genevisible; Q01130; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; NAS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IEA:InterPro.
DR GO; GO:0008380; P:RNA splicing; TAS:ProtInc.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR003954; RRM_dom_euk.
DR InterPro; IPR034893; SRSF2-like.
DR PANTHER; PTHR23147:SF119; PTHR23147:SF119; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SMART; SM00361; RRM_1; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.10, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT CHAIN 2..221
FT /note="Serine/arginine-rich splicing factor 2"
FT /id="PRO_0000081918"
FT DOMAIN 14..92
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 92..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..187
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..212
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.10, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 22
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 52
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21157427"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 108..119
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056153"
FT CONFLICT 38
FT /note="G -> R (in Ref. 1; AAA60306)"
FT /evidence="ECO:0000305"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:2LEA"
FT STRAND 15..20
FT /evidence="ECO:0007829|PDB:2KN4"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:2KN4"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:2KN4"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:2LEA"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:2KN4"
FT HELIX 65..74
FT /evidence="ECO:0007829|PDB:2KN4"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:2KN4"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:2KN4"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:2LEB"
SQ SEQUENCE 221 AA; 25476 MW; 68121AC4D35714FA CRC64;
MSYGRPPPDV EGMTSLKVDN LTYRTSPDTL RRVFEKYGRV GDVYIPRDRY TKESRGFAFV
RFHDKRDAED AMDAMDGAVL DGRELRVQMA RYGRPPDSHH SRRGPPPRRY GGGGYGRRSR
SPRRRRRSRS RSRSRSRSRS RSRYSRSKSR SRTRSRSRST SKSRSARRSK SKSSSVSRSR
SRSRSRSRSR SPPPVSKRES KSRSRSKSPP KSPEEEGAVS S
