PRP19_HUMAN
ID PRP19_HUMAN Reviewed; 504 AA.
AC Q9UMS4;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Pre-mRNA-processing factor 19 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:11435423};
DE AltName: Full=Nuclear matrix protein 200 {ECO:0000303|PubMed:11082287};
DE AltName: Full=PRP19/PSO4 homolog {ECO:0000303|PubMed:12960389};
DE Short=hPso4 {ECO:0000303|PubMed:12960389};
DE AltName: Full=RING-type E3 ubiquitin transferase PRP19 {ECO:0000305};
DE AltName: Full=Senescence evasion factor {ECO:0000303|PubMed:16332694};
GN Name=PRPF19 {ECO:0000312|HGNC:HGNC:17896};
GN Synonyms=NMP200 {ECO:0000303|PubMed:11082287},
GN PRP19 {ECO:0000303|PubMed:11435423}, SNEV {ECO:0000303|PubMed:16332694};
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], PROTEIN SEQUENCE OF 32-40; 100-115; 179-187;
RP 192-199 AND 334-342, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND CHROMOSOMAL LOCATION.
RC TISSUE=Cervix;
RX PubMed=11082287; DOI=10.1006/excr.2000.5025;
RA Gotzmann J., Gerner C., Meissner M., Holzmann K., Grimm R., Mikulits W.,
RA Sauermann G.;
RT "hNMP 200: a novel human common nuclear matrix protein combining structural
RT and regulatory functions.";
RL Exp. Cell Res. 261:166-179(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP INTERACTION WITH DNTT.
RX PubMed=12960389; DOI=10.1073/pnas.1631060100;
RA Mahajan K.N., Mitchell B.S.;
RT "Role of human Pso4 in mammalian DNA repair and association with terminal
RT deoxynucleotidyl transferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10746-10751(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 2-27; 33-56; 77-93; 101-115; 193-206; 209-236; 252-261
RP AND 266-303, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 2-27; 33-56; 63-93; 101-115; 193-206; 209-261; 266-303;
RP 344-375 AND 429-439, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 32-40, AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood;
RX PubMed=10404385;
RX DOI=10.1002/(sici)1097-4644(19990801)74:2<145::aid-jcb1>3.0.co;2-#;
RA Gerner C., Holzmann K., Meissner M., Gotzmann J., Grimm R., Sauermann G.;
RT "Reassembling proteins and chaperones in human nuclear matrix protein
RT fractions.";
RL J. Cell. Biochem. 74:145-151(1999).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11435423; DOI=10.1074/jbc.m102755200;
RA Hatakeyama S., Yada M., Matsumoto M., Ishida N., Nakayama K.I.;
RT "U box proteins as a new family of ubiquitin-protein ligases.";
RL J. Biol. Chem. 276:33111-33120(2001).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SPLICEOSOMAL
RP C COMPLEX.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=16332694; DOI=10.1093/nar/gki986;
RA Grillari J., Ajuh P., Stadler G., Loescher M., Voglauer R., Ernst W.,
RA Chusainow J., Eisenhaber F., Pokar M., Fortschegger K., Grey M.,
RA Lamond A.I., Katinger H.;
RT "SNEV is an evolutionarily conserved splicing factor whose oligomerization
RT is necessary for spliceosome assembly.";
RL Nucleic Acids Res. 33:6868-6883(2005).
RN [11]
RP INTERACTION WITH PSMB4, AND FUNCTION.
RX PubMed=15660529; DOI=10.1042/bj20041517;
RA Loescher M., Fortschegger K., Ritter G., Wostry M., Voglauer R.,
RA Schmid J.A., Watters S., Rivett A.J., Ajuh P., Lamond A.I., Katinger H.,
RA Grillari J.;
RT "Interaction of U-box E3 ligase SNEV with PSMB4, the beta7 subunit of the
RT 20 S proteasome.";
RL Biochem. J. 388:593-603(2005).
RN [12]
RP FUNCTION, AND IDENTIFICATION AS A COMPONENT OF THE PSO4 COMPLEX.
RX PubMed=16223718; DOI=10.1074/jbc.m508453200;
RA Zhang N., Kaur R., Lu X., Shen X., Li L., Legerski R.J.;
RT "The Pso4 mRNA splicing and DNA repair complex interacts with WRN for
RT processing of DNA interstrand cross-links.";
RL J. Biol. Chem. 280:40559-40567(2005).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16388800; DOI=10.1016/j.yexcr.2005.11.025;
RA Voglauer R., Chang M.W.-F., Dampier B., Wieser M., Baumann K.,
RA Sterovsky T., Schreiber M., Katinger H., Grillari J.;
RT "SNEV overexpression extends the life span of human endothelial cells.";
RL Exp. Cell Res. 312:746-759(2006).
RN [14]
RP FUNCTION.
RX PubMed=17349974; DOI=10.1016/j.bbrc.2007.02.134;
RA Sihn C.R., Cho S.Y., Lee J.H., Lee T.R., Kim S.H.;
RT "Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory
RT subunit of 26S proteasome.";
RL Biochem. Biophys. Res. Commun. 356:175-180(2007).
RN [15]
RP FUNCTION, AND IDENTIFICATION AS PART OF THE XAB2 COMPLEX.
RX PubMed=17981804; DOI=10.1074/jbc.m706647200;
RA Kuraoka I., Ito S., Wada T., Hayashida M., Lee L., Saijo M., Nakatsu Y.,
RA Matsumoto M., Matsunaga T., Handa H., Qin J., Nakatani Y., Tanaka K.;
RT "Isolation of XAB2 complex involved in pre-mRNA splicing, transcription,
RT and transcription-coupled repair.";
RL J. Biol. Chem. 283:940-950(2008).
RN [16]
RP FUNCTION, INTERACTION WITH SETMAR, AND SUBCELLULAR LOCATION.
RX PubMed=18263876; DOI=10.1074/jbc.m800150200;
RA Beck B.D., Park S.J., Lee Y.J., Roman Y., Hromas R.A., Lee S.H.;
RT "Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase
RT function in DNA repair.";
RL J. Biol. Chem. 283:9023-9030(2008).
RN [17]
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 [18]
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 [19]
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 [20]
RP INTERACTION WITH APEX1, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19188445; DOI=10.1128/mcb.01337-08;
RA Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M.,
RA Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A.,
RA Quadrifoglio F., Tell G.;
RT "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the
RT rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-122 AND LYS-261, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., 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 [22]
RP FUNCTION, AND INTERACTION WITH PRPF3.
RX PubMed=20595234; DOI=10.1101/gad.1925010;
RA Song E.J., Werner S.L., Neubauer J., Stegmeier F., Aspden J., Rio D.,
RA Harper J.W., Elledge S.J., Kirschner M.W., Rape M.;
RT "The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control
RT reversible ubiquitination at the spliceosome.";
RL Genes Dev. 24:1434-1447(2010).
RN [23]
RP IDENTIFICATION AS A COMPONENT OF THE PRP19-CDC5L SPLICING COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH CDC5L; PLRG1 AND BCAS2.
RX PubMed=20176811; DOI=10.1128/mcb.01505-09;
RA Grote M., Wolf E., Will C.L., Lemm I., Agafonov D.E., Schomburg A.,
RA Fischle W., Urlaub H., Luhrmann R.;
RT "Molecular architecture of the human Prp19/CDC5L complex.";
RL Mol. Cell. Biol. 30:2105-2119(2010).
RN [24]
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 [25]
RP FUNCTION, AND INTERACTION WITH U2AF2.
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 [26]
RP INTERACTION WITH USB1.
RX PubMed=23022480; DOI=10.1016/j.celrep.2012.08.031;
RA Shchepachev V., Wischnewski H., Missiaglia E., Soneson C., Azzalin C.M.;
RT "Mpn1, mutated in poikiloderma with neutropenia protein 1, is a conserved
RT 3'-to-5' RNA exonuclease processing U6 small nuclear RNA.";
RL Cell Rep. 2:855-865(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=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 [28]
RP INTERACTION WITH CWC22 AND EIF4A3.
RX PubMed=22961380; DOI=10.1038/nsmb.2380;
RA Barbosa I., Haque N., Fiorini F., Barrandon C., Tomasetto C.,
RA Blanchette M., Le Hir H.;
RT "Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes
RT exon junction complex assembly.";
RL Nat. Struct. Mol. Biol. 19:983-990(2012).
RN [29]
RP FUNCTION, INTERACTION WITH RPA1 AND RPA2, DOMAIN, AND MUTAGENESIS OF
RP TYR-405.
RX PubMed=24332808; DOI=10.1016/j.molcel.2013.11.002;
RA Marechal A., Li J.M., Ji X.Y., Wu C.S., Yazinski S.A., Nguyen H.D., Liu S.,
RA Jimenez A.E., Jin J., Zou L.;
RT "PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives
RT ATR activation via a ubiquitin-mediated circuitry.";
RL Mol. Cell 53:235-246(2014).
RN [30]
RP INTERACTION WITH KNSTRN.
RX PubMed=24718257; DOI=10.1371/journal.pone.0092712;
RA Lu S., Wang R., Cai C., Liang J., Xu L., Miao S., Wang L., Song W.;
RT "Small kinetochore associated protein (SKAP) promotes UV-induced cell
RT apoptosis through negatively regulating pre-mRNA processing factor 19
RT (Prp19).";
RL PLoS ONE 9:E92712-E92712(2014).
RN [31] {ECO:0007744|PDB:4LG8}
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 169-504.
RX PubMed=28962858; DOI=10.1016/j.bbrc.2017.09.145;
RA Zhang Y., Li Y., Liang X., Zhu Z., Sun H., He H., Min J., Liao S., Liu Y.;
RT "Crystal structure of the WD40 domain of human PRPF19.";
RL Biochem. Biophys. Res. Commun. 493:1250-1253(2017).
RN [32] {ECO:0007744|PDB:5XJC}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28502770; DOI=10.1016/j.cell.2017.04.033;
RA Zhang X., Yan C., Hang J., Finci L.I., Lei J., Shi Y.;
RT "An Atomic Structure of the Human Spliceosome.";
RL Cell 169:918-929(2017).
RN [33] {ECO:0007744|PDB:5MQF}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.90 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28076346; DOI=10.1038/nature21079;
RA Bertram K., Agafonov D.E., Liu W.T., Dybkov O., Will C.L., Hartmuth K.,
RA Urlaub H., Kastner B., Stark H., Luhrmann R.;
RT "Cryo-EM structure of a human spliceosome activated for step 2 of
RT splicing.";
RL Nature 542:318-323(2017).
RN [34] {ECO:0007744|PDB:5Z56, ECO:0007744|PDB:5Z57}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.10 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29360106; DOI=10.1038/cr.2018.14;
RA Zhang X., Yan C., Zhan X., Li L., Lei J., Shi Y.;
RT "Structure of the human activated spliceosome in three conformational
RT states.";
RL Cell Res. 28:307-322(2018).
RN [35] {ECO:0007744|PDB:5YZG}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29301961; DOI=10.1126/science.aar6401;
RA Zhan X., Yan C., Zhang X., Lei J., Shi Y.;
RT "Structure of a human catalytic step I spliceosome.";
RL Science 359:537-545(2018).
RN [36] {ECO:0007744|PDB:6QDV}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=30705154; DOI=10.1126/science.aaw5569;
RA Fica S.M., Oubridge C., Wilkinson M.E., Newman A.J., Nagai K.;
RT "A human postcatalytic spliceosome structure reveals essential roles of
RT metazoan factors for exon ligation.";
RL Science 363:710-714(2019).
CC -!- FUNCTION: Ubiquitin-protein ligase which is a core component of several
CC complexes mainly involved pre-mRNA splicing and DNA repair. Required
CC for pre-mRNA splicing as component of the spliceosome (PubMed:28502770,
CC PubMed:28076346, PubMed:29360106, PubMed:29301961, PubMed:30705154).
CC Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which
CC is part of the spliceosome and participates in its assembly, its
CC remodeling and is required for its activity. During assembly of the
CC spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4
CC spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its
CC recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-
CC snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA
CC polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also
CC couple the transcriptional and spliceosomal machineries
CC (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also
CC involved in pre-mRNA splicing, transcription and transcription-coupled
CC repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19,
CC as part of the PRP19-CDC5L complex, plays a role in the DNA damage
CC response/DDR. It is recruited to the sites of DNA damage by the RPA
CC complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-
CC linked polyubiquitination of the RPA complex allows the recruitment of
CC the ATR-ATRIP complex and the activation of ATR, a master regulator of
CC the DNA damage response (PubMed:24332808). May also play a role in DNA
CC double-strand break (DSB) repair by recruiting the repair factor SETMAR
CC to altered DNA (PubMed:18263876). As part of the PSO4 complex may also
CC be involved in the DNA interstrand cross-links/ICLs repair process
CC (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked
CC polyubiquitination of substrates and play a role in proteasomal
CC degradation (PubMed:11435423). May play a role in the biogenesis of
CC lipid droplets (By similarity). May play a role in neural
CC differentiation possibly through its function as part of the
CC spliceosome (By similarity). {ECO:0000250|UniProtKB:Q99KP6,
CC ECO:0000250|UniProtKB:Q9JMJ4, ECO:0000269|PubMed:11082287,
CC ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389,
CC ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718,
CC ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:16388800,
CC ECO:0000269|PubMed:17349974, ECO:0000269|PubMed:18263876,
CC ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:24332808,
CC ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770,
CC ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106,
CC ECO:0000269|PubMed:30705154, ECO:0000303|PubMed:17981804,
CC ECO:0000303|PubMed:20595234}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:11435423};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11435423}.
CC -!- SUBUNIT: Homotetramer. Component of activated, catalytic and post-
CC catalytic spliceosomes (PubMed:28502770, PubMed:28076346,
CC PubMed:29360106, PubMed:29301961, PubMed:30705154). Component of the
CC Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes
CC described as PRP19-CDC5L splicing complex and PSO4 complex. A
CC homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of
CC those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct
CC within this core complex. At least three less stably associated
CC proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The
CC Prp19 complex associates with the spliceosome during its assembly and
CC remodeling recruiting additional proteins. Component of the XAB2
CC complex, a multimeric protein complex composed of XAB2, PRPF19, AQR,
CC ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-
CC independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L
CC complex is recruited to the sites of DNA repair where it interacts with
CC the replication protein A complex (RPA). Interacts with SETMAR;
CC required for SETMAR recruitment to site of DNA damage. Interacts with
CC U2AF2; the interaction is direct and recruits the Prp19 complex to RNA
CC polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with
CC PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with PSMC5 (By
CC similarity). Interacts with KNSTRN (PubMed:24718257). Interacts (via N-
CC terminus) with CDC5L (By similarity). Interacts with KHDC4
CC (PubMed:19641227). Interacts with USB1 (PubMed:23022480).
CC {ECO:0000250|UniProtKB:Q99KP6, ECO:0000250|UniProtKB:Q9JMJ4,
CC ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12960389,
CC ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718,
CC ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:17981804,
CC ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:19188445,
CC ECO:0000269|PubMed:19641227, ECO:0000269|PubMed:20176811,
CC ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:21536736,
CC ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:23022480,
CC ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:24718257,
CC ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770,
CC ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106,
CC ECO:0000269|PubMed:30705154}.
CC -!- INTERACTION:
CC Q9UMS4; O75934: BCAS2; NbExp=7; IntAct=EBI-395746, EBI-1050106;
CC Q9UMS4; O60508: CDC40; NbExp=3; IntAct=EBI-395746, EBI-2557812;
CC Q9UMS4; Q99459: CDC5L; NbExp=11; IntAct=EBI-395746, EBI-374880;
CC Q9UMS4; Q6P2Q9: PRPF8; NbExp=2; IntAct=EBI-395746, EBI-538479;
CC Q9UMS4; P98175: RBM10; NbExp=2; IntAct=EBI-395746, EBI-721525;
CC Q9UMS4; P52756: RBM5; NbExp=8; IntAct=EBI-395746, EBI-714003;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11082287,
CC ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:19188445,
CC ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:28076346,
CC ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961,
CC ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30705154}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:11082287}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000269|PubMed:11082287}. Cytoplasm
CC {ECO:0000269|PubMed:11435423}. Lipid droplet
CC {ECO:0000250|UniProtKB:Q99KP6}. Note=Nucleoplasmic in interphase cells.
CC Irregularly distributed in anaphase cells. In prophase cells, uniformly
CC distributed, but not associated with condensing chromosomes. Found in
CC extrachromosomal regions in metaphase cells. Mainly localized to the
CC mitotic spindle apparatus when chromosomes segregate during anaphase.
CC When nuclei reform during late telophase, uniformly distributed in
CC daughter cells and displays no preferred association with decondensing
CC chromatin. Recruited on damaged DNA at sites of double-strand break.
CC {ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:18263876}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Weakly expressed in senescent cells of
CC different tissue origins. Highly expressed in tumor cell lines.
CC {ECO:0000269|PubMed:10404385, ECO:0000269|PubMed:11082287,
CC ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389,
CC ECO:0000269|PubMed:16388800}.
CC -!- INDUCTION: By gamma irradiation and chemical mutagens but not by UV
CC irradiation. {ECO:0000269|PubMed:12960389}.
CC -!- DOMAIN: The 7 WD repeats are necessary and sufficient to support
CC interaction with the RPA complex. {ECO:0000269|PubMed:24332808}.
CC -!- SIMILARITY: Belongs to the WD repeat PRP19 family. {ECO:0000305}.
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DR EMBL; AJ131186; CAB51857.1; -; mRNA.
DR EMBL; BC008719; AAH08719.1; -; mRNA.
DR EMBL; BC018665; AAH18665.1; -; mRNA.
DR EMBL; BC018698; AAH18698.1; -; mRNA.
DR CCDS; CCDS7995.1; -.
DR RefSeq; NP_055317.1; NM_014502.4.
DR PDB; 4LG8; X-ray; 1.89 A; A=169-504.
DR PDB; 5MQF; EM; 5.90 A; G/H/I/J=1-504.
DR PDB; 5XJC; EM; 3.60 A; q/r/s/t=1-504.
DR PDB; 5YZG; EM; 4.10 A; q/r/s/t=1-504.
DR PDB; 5Z56; EM; 5.10 A; q/r/s/t=1-504.
DR PDB; 5Z57; EM; 6.50 A; q/r/s/t=1-504.
DR PDB; 6FF7; EM; 4.50 A; G/H/I/J=1-504.
DR PDB; 6ICZ; EM; 3.00 A; q/r/s/t=1-504.
DR PDB; 6ID0; EM; 2.90 A; q/r/s/t=1-504.
DR PDB; 6ID1; EM; 2.86 A; q/r/s/t=1-504.
DR PDB; 6QDV; EM; 3.30 A; t/u/v/w=1-504.
DR PDB; 7A5P; EM; 5.00 A; G/H/I/J=1-504.
DR PDBsum; 4LG8; -.
DR PDBsum; 5MQF; -.
DR PDBsum; 5XJC; -.
DR PDBsum; 5YZG; -.
DR PDBsum; 5Z56; -.
DR PDBsum; 5Z57; -.
DR PDBsum; 6FF7; -.
DR PDBsum; 6ICZ; -.
DR PDBsum; 6ID0; -.
DR PDBsum; 6ID1; -.
DR PDBsum; 6QDV; -.
DR PDBsum; 7A5P; -.
DR AlphaFoldDB; Q9UMS4; -.
DR SMR; Q9UMS4; -.
DR BioGRID; 118151; 326.
DR ComplexPortal; CPX-5824; PRP19-CDC5L complex.
DR CORUM; Q9UMS4; -.
DR DIP; DIP-32978N; -.
DR IntAct; Q9UMS4; 111.
DR MINT; Q9UMS4; -.
DR STRING; 9606.ENSP00000227524; -.
DR MoonDB; Q9UMS4; Predicted.
DR GlyGen; Q9UMS4; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; Q9UMS4; -.
DR MetOSite; Q9UMS4; -.
DR PhosphoSitePlus; Q9UMS4; -.
DR SwissPalm; Q9UMS4; -.
DR BioMuta; PRPF19; -.
DR DMDM; 55976619; -.
DR REPRODUCTION-2DPAGE; IPI00004968; -.
DR SWISS-2DPAGE; Q9UMS4; -.
DR CPTAC; CPTAC-576; -.
DR CPTAC; CPTAC-577; -.
DR EPD; Q9UMS4; -.
DR jPOST; Q9UMS4; -.
DR MassIVE; Q9UMS4; -.
DR MaxQB; Q9UMS4; -.
DR PaxDb; Q9UMS4; -.
DR PeptideAtlas; Q9UMS4; -.
DR PRIDE; Q9UMS4; -.
DR ProteomicsDB; 85207; -.
DR Antibodypedia; 3247; 319 antibodies from 34 providers.
DR DNASU; 27339; -.
DR Ensembl; ENST00000227524.9; ENSP00000227524.4; ENSG00000110107.9.
DR GeneID; 27339; -.
DR KEGG; hsa:27339; -.
DR MANE-Select; ENST00000227524.9; ENSP00000227524.4; NM_014502.5; NP_055317.1.
DR UCSC; uc001nqf.4; human.
DR CTD; 27339; -.
DR DisGeNET; 27339; -.
DR GeneCards; PRPF19; -.
DR HGNC; HGNC:17896; PRPF19.
DR HPA; ENSG00000110107; Low tissue specificity.
DR MIM; 608330; gene.
DR neXtProt; NX_Q9UMS4; -.
DR OpenTargets; ENSG00000110107; -.
DR PharmGKB; PA134941355; -.
DR VEuPathDB; HostDB:ENSG00000110107; -.
DR eggNOG; KOG0289; Eukaryota.
DR GeneTree; ENSGT00940000153662; -.
DR HOGENOM; CLU_023894_1_1_1; -.
DR InParanoid; Q9UMS4; -.
DR OMA; VTRVIYH; -.
DR OrthoDB; 1049599at2759; -.
DR PhylomeDB; Q9UMS4; -.
DR TreeFam; TF105919; -.
DR PathwayCommons; Q9UMS4; -.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR SignaLink; Q9UMS4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 27339; 819 hits in 1090 CRISPR screens.
DR ChiTaRS; PRPF19; human.
DR GeneWiki; PRPF19; -.
DR GenomeRNAi; 27339; -.
DR Pharos; Q9UMS4; Tbio.
DR PRO; PR:Q9UMS4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UMS4; protein.
DR Bgee; ENSG00000110107; Expressed in pons and 205 other tissues.
DR ExpressionAtlas; Q9UMS4; baseline and differential.
DR Genevisible; Q9UMS4; HS.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000974; C:Prp19 complex; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0005681; C:spliceosomal complex; IPI:ComplexPortal.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; IBA:GO_Central.
DR GO; GO:0071007; C:U2-type catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0008610; P:lipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; IEA:Ensembl.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0000245; P:spliceosomal complex assembly; IMP:BHF-UCL.
DR GO; GO:0000244; P:spliceosomal tri-snRNP complex assembly; IDA:UniProtKB.
DR DisProt; DP01161; -.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR013915; Pre-mRNA_splic_Prp19.
DR InterPro; IPR038959; Prp19.
DR InterPro; IPR000772; Ricin_B_lectin.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR43995; PTHR43995; 1.
DR Pfam; PF08606; Prp19; 1.
DR Pfam; PF04564; U-box; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00504; Ubox; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51698; U_BOX; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 4.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; DNA damage; DNA repair; Lipid droplet;
KW mRNA processing; mRNA splicing; Nucleus; Reference proteome; Repeat;
KW Spliceosome; Transferase; Ubl conjugation pathway; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895"
FT CHAIN 2..504
FT /note="Pre-mRNA-processing factor 19"
FT /id="PRO_0000051145"
FT DOMAIN 2..73
FT /note="U-box"
FT REPEAT 219..259
FT /note="WD 1"
FT REPEAT 262..301
FT /note="WD 2"
FT REPEAT 304..345
FT /note="WD 3"
FT REPEAT 348..387
FT /note="WD 4"
FT REPEAT 390..429
FT /note="WD 5"
FT REPEAT 433..472
FT /note="WD 6"
FT REPEAT 473..503
FT /note="WD 7"
FT REGION 68..223
FT /note="May mediate interaction with PSMC5"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895"
FT MOD_RES 122
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 179
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 244
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 261
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MUTAGEN 405
FT /note="Y->A: Loss of interaction with the RPA complex and
FT loss of recruitment to sites of DNA damage."
FT /evidence="ECO:0000269|PubMed:24332808"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6ID1"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:6ID1"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:6ID1"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:6ID1"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:6ID0"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:6ID1"
FT HELIX 76..132
FT /evidence="ECO:0007829|PDB:6ID1"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 293..296
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 318..325
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 335..337
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 353..358
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 362..369
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 374..378
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 379..382
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 395..400
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 404..411
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 421..424
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 425..431
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 438..443
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 447..461
FT /evidence="ECO:0007829|PDB:4LG8"
FT TURN 462..465
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 478..483
FT /evidence="ECO:0007829|PDB:4LG8"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 490..494
FT /evidence="ECO:0007829|PDB:4LG8"
FT STRAND 499..503
FT /evidence="ECO:0007829|PDB:4LG8"
SQ SEQUENCE 504 AA; 55181 MW; B34C37496E8AA032 CRC64;
MSLICSISNE VPEHPCVSPV SNHVYERRLI EKYIAENGTD PINNQPLSEE QLIDIKVAHP
IRPKPPSATS IPAILKALQD EWDAVMLHSF TLRQQLQTTR QELSHALYQH DAACRVIARL
TKEVTAAREA LATLKPQAGL IVPQAVPSSQ PSVVGAGEPM DLGELVGMTP EIIQKLQDKA
TVLTTERKKR GKTVPEELVK PEELSKYRQV ASHVGLHSAS IPGILALDLC PSDTNKILTG
GADKNVVVFD KSSEQILATL KGHTKKVTSV VFHPSQDLVF SASPDATIRI WSVPNASCVQ
VVRAHESAVT GLSLHATGDY LLSSSDDQYW AFSDIQTGRV LTKVTDETSG CSLTCAQFHP
DGLIFGTGTM DSQIKIWDLK ERTNVANFPG HSGPITSIAF SENGYYLATA ADDSSVKLWD
LRKLKNFKTL QLDNNFEVKS LIFDQSGTYL ALGGTDVQIY ICKQWTEILH FTEHSGLTTG
VAFGHHAKFI ASTGMDRSLK FYSL
