ID PRPF3_HUMAN Reviewed; 683 AA. AC O43395; B4DSY9; O43446; Q5VT54; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2003, sequence version 2. DT 27-MAR-2024, entry version 215. DE RecName: Full=U4/U6 small nuclear ribonucleoprotein Prp3; DE AltName: Full=Pre-mRNA-splicing factor 3; DE Short=hPrp3; DE AltName: Full=U4/U6 snRNP 90 kDa protein; GN Name=PRPF3; Synonyms=HPRP3 {ECO:0000303|PubMed:11773002}, PRP3; 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), INTERACTION WITH PRPF4 AND U4/U5/U6 RP SNRNPS, AND SUBCELLULAR LOCATION. RX PubMed=9328476; DOI=10.1093/hmg/6.12.2117; RA Wang A., Forman-Kay J., Luo Y., Luo M., Chow Y.-H., Plumb J., Friesen J.D., RA Tsui L.-C., Heng H.H.Q., Woolford J.L. Jr., Hu J.; RT "Identification and characterization of human genes encoding Hprp3p and RT Hprp4p, interacting components of the spliceosome."; RL Hum. Mol. Genet. 6:2117-2126(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 93-101; RP 253-267; 351-361; 409-428 AND 560-576, INTERACTION WITH PPIH; PRPF4 AND RP U4/U6 SNRNPS, AND SUBCELLULAR LOCATION. RC TISSUE=Neuroepithelium; RX PubMed=9404889; RA Horowitz D.S., Kobayashi R., Krainer A.R.; RT "A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a RT complex associated with U4/U6 snRNPs."; RL RNA 3:1374-1387(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye, 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 [7] RP INTERACTION WITH SART3, AND REGION. RX PubMed=15314151; DOI=10.1128/mcb.24.17.7392-7401.2004; RA Medenbach J., Schreiner S., Liu S., Luhrmann R., Bindereif A.; RT "Human U4/U6 snRNP recycling factor p110: mutational analysis reveals the RT function of the tetratricopeptide repeat domain in recycling."; RL Mol. Cell. Biol. 24:7392-7401(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP SUBUNIT. RX PubMed=16723661; DOI=10.1261/rna.55406; RA Liu S., Rauhut R., Vornlocher H.-P., Luehrmann R.; RT "The network of protein-protein interactions within the human U4/U6.U5 tri- RT snRNP."; RL RNA 12:1418-1430(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-167, AND 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, AND IDENTIFICATION BY RP 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 [14] RP FUNCTION, INTERACTION WITH PRPF8; PRPF19 AND SART3, UBIQUITINATION BY RP PRPF19, AND DEUBIQUITINATION BY USP4. 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; THR-167 AND SER-619, AND RP IDENTIFICATION BY MASS 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 [16] 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND SER-619, 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619, 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 [20] RP INTERACTION WITH ERCC6. RX PubMed=26030138; DOI=10.1371/journal.pone.0128558; RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G., RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.; RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin RT Dynamics."; RL PLoS ONE 10:E0128558-E0128558(2015). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-139; LYS-244 AND LYS-252, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [22] RP STRUCTURE BY NMR OF 1-79. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of PWI domain in U4/U6 small nuclear ribonucleoprotein RT PRP3(HPRP3)."; RL Submitted (NOV-2005) to the PDB data bank. RN [23] {ECO:0007744|PDB:3JCR} RP STRUCTURE BY ELECTRON MICROSCOPY (7.00 ANGSTROMS), SUBCELLULAR LOCATION, RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=26912367; DOI=10.1126/science.aad2085; RA Agafonov D.E., Kastner B., Dybkov O., Hofele R.V., Liu W.T., Urlaub H., RA Luhrmann R., Stark H.; RT "Molecular architecture of the human U4/U6.U5 tri-snRNP."; RL Science 351:1416-1420(2016). RN [24] {ECO:0007744|PDB:5O9Z} RP STRUCTURE BY ELECTRON MICROSCOPY (4.50 ANGSTROMS), SUBCELLULAR LOCATION, RP SUBUNIT, FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=28781166; DOI=10.1016/j.cell.2017.07.011; RA Bertram K., Agafonov D.E., Dybkov O., Haselbach D., Leelaram M.N., RA Will C.L., Urlaub H., Kastner B., Luhrmann R., Stark H.; RT "Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for RT Activation."; RL Cell 170:701-713(2017). RN [25] RP VARIANTS RP18 SER-493 AND MET-494, AND TISSUE SPECIFICITY. RX PubMed=11773002; DOI=10.1093/hmg/11.1.87; RA Chakarova C.F., Hims M.M., Bolz H., Abu-Safieh L., Patel R.J., RA Papaioannou M.G., Inglehearn C.F., Keen T.J., Willis C., Moore A.T., RA Rosenberg T., Webster A.R., Bird A.C., Gal A., Hunt D., Vithana E.N., RA Bhattacharya S.S.; RT "Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, RT implicated in autosomal dominant retinitis pigmentosa."; RL Hum. Mol. Genet. 11:87-92(2002). RN [26] RP VARIANT RP18 MET-494. RX PubMed=12714658; DOI=10.1167/iovs.02-0871; RA Martinez-Gimeno M., Gamundi M.J., Hernan I., Maseras M., Milla E., RA Ayuso C., Garcia-Sandoval B., Beneyto M., Vilela C., Baiget M., RA Antinolo G., Carballo M.; RT "Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 RT in Spanish families with autosomal dominant retinitis pigmentosa."; RL Invest. Ophthalmol. Vis. Sci. 44:2171-2177(2003). RN [27] RP CHARACTERIZATION OF VARIANT RP18 MET-494, SUBUNIT, AND SUBCELLULAR RP LOCATION. RX PubMed=17932117; DOI=10.1093/hmg/ddm300; RA Gonzalez-Santos J.M., Cao H., Duan R.C., Hu J.; RT "Mutation in the splicing factor Hprp3p linked to retinitis pigmentosa RT impairs interactions within the U4/U6 snRNP complex."; RL Hum. Mol. Genet. 17:225-239(2008). CC -!- FUNCTION: Plays a role in pre-mRNA splicing as component of the U4/U6- CC U5 tri-snRNP complex that is involved in spliceosome assembly, and as CC component of the precatalytic spliceosome (spliceosome B complex). CC {ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28781166, CC ECO:0000305|PubMed:20595234}. CC -!- SUBUNIT: Component of the precatalytic spliceosome (spliceosome B CC complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP CC complex, a building block of the precatalytic spliceosome (spliceosome CC B complex) (PubMed:9328476, PubMed:9404889, PubMed:28781166, CC PubMed:26912367, PubMed:17932117). The U4/U6-U5 tri-snRNP complex is CC composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, CC PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, CC SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 CC and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 CC (PubMed:16723661, PubMed:26912367). Interacts directly with PRPF4 CC (PubMed:9328476, PubMed:9404889, PubMed:17932117). Part of a CC heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in CC the absence of RNA (PubMed:9404889). Interacts with SART3; the CC interaction is direct and recruits the deubiquitinase USP4 to PRPF3 CC (PubMed:15314151, PubMed:20595234). Interacts with PRPF19. Interacts CC ('Lys-63'-linked polyubiquitinated) with PRPF8 (via the MPN (JAB/Mov34) CC domain); may stabilize the U4/U6-U5 tri-snRNP complex CC (PubMed:20595234). Interacts with ERCC6 (PubMed:26030138). CC {ECO:0000269|PubMed:15314151, ECO:0000269|PubMed:16723661, CC ECO:0000269|PubMed:17932117, ECO:0000269|PubMed:20595234, CC ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:26912367, CC ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:9328476, CC ECO:0000269|PubMed:9404889}. CC -!- INTERACTION: CC O43395; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-744322, EBI-3866279; CC O43395; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-744322, EBI-11977221; CC O43395; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-744322, EBI-739624; CC O43395; Q92997: DVL3; NbExp=2; IntAct=EBI-744322, EBI-739789; CC O43395; Q8IZU0: FAM9B; NbExp=9; IntAct=EBI-744322, EBI-10175124; CC O43395; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-744322, EBI-11977403; CC O43395; Q08379: GOLGA2; NbExp=3; IntAct=EBI-744322, EBI-618309; CC O43395; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-744322, EBI-473189; CC O43395; O75031: HSF2BP; NbExp=3; IntAct=EBI-744322, EBI-7116203; CC O43395; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-744322, EBI-1216080; CC O43395; P55081: MFAP1; NbExp=2; IntAct=EBI-744322, EBI-1048159; CC O43395; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-744322, EBI-10172526; CC O43395; Q96RE7: NACC1; NbExp=3; IntAct=EBI-744322, EBI-7950997; CC O43395; Q8N5F7: NKAP; NbExp=2; IntAct=EBI-744322, EBI-721539; CC O43395; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-744322, EBI-3920396; CC O43395; Q9H4L5: OSBPL3; NbExp=3; IntAct=EBI-744322, EBI-1051317; CC O43395; Q8IXK0-5: PHC2; NbExp=3; IntAct=EBI-744322, EBI-11527347; CC O43395; P78356-2: PIP4K2B; NbExp=3; IntAct=EBI-744322, EBI-11532361; CC O43395; O43395: PRPF3; NbExp=2; IntAct=EBI-744322, EBI-744322; CC O43395; O94906: PRPF6; NbExp=3; IntAct=EBI-744322, EBI-536755; CC O43395; O43242: PSMD3; NbExp=3; IntAct=EBI-744322, EBI-357622; CC O43395; Q15276: RABEP1; NbExp=3; IntAct=EBI-744322, EBI-447043; CC O43395; Q2KHN1: RNF151; NbExp=3; IntAct=EBI-744322, EBI-12002474; CC O43395; O43290: SART1; NbExp=4; IntAct=EBI-744322, EBI-607761; CC O43395; Q13435: SF3B2; NbExp=2; IntAct=EBI-744322, EBI-749111; CC O43395; Q8TBC3: SHKBP1; NbExp=3; IntAct=EBI-744322, EBI-724292; CC O43395; O95391: SLU7; NbExp=2; IntAct=EBI-744322, EBI-750559; CC O43395; O75940: SMNDC1; NbExp=2; IntAct=EBI-744322, EBI-1052641; CC O43395; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-744322, EBI-2212028; CC O43395; Q9HCM9: TRIM39; NbExp=4; IntAct=EBI-744322, EBI-739510; CC O43395; Q9HCM9-2: TRIM39; NbExp=8; IntAct=EBI-744322, EBI-11523450; CC O43395; Q6FI91: TSPYL; NbExp=3; IntAct=EBI-744322, EBI-723389; CC O43395; P40222: TXLNA; NbExp=3; IntAct=EBI-744322, EBI-359793; CC O43395; P26368: U2AF2; NbExp=2; IntAct=EBI-744322, EBI-742339; CC O43395; P26368-2: U2AF2; NbExp=3; IntAct=EBI-744322, EBI-11097439; CC O43395; Q8WW38: ZFPM2; NbExp=3; IntAct=EBI-744322, EBI-947213; CC O43395; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-744322, EBI-527853; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17932117, CC ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28781166, CC ECO:0000269|PubMed:9328476, ECO:0000269|PubMed:9404889}. Nucleus CC speckle. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43395-1; Sequence=Displayed; CC Name=2; CC IsoId=O43395-3; Sequence=VSP_056265, VSP_056266, VSP_056267; CC -!- TISSUE SPECIFICITY: Highly expressed in retina, liver, kidney and CC blood. Detected at lower levels in heart and brain. CC {ECO:0000269|PubMed:11773002}. CC -!- PTM: Ubiquitinated. Undergoes 'Lys-63'-linked polyubiquitination by CC PRPF19 and deubiquitination by USP4. 'Lys-63'-linked ubiquitination CC increases the affinity for PRPF8 and may regulate the assembly of the CC U4/U6-U5 tri-snRNP complex. {ECO:0000269|PubMed:20595234}. CC -!- DISEASE: Retinitis pigmentosa 18 (RP18) [MIM:601414]: A retinal CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. As their CC condition progresses, they lose their far peripheral visual field and CC eventually central vision as well. {ECO:0000269|PubMed:11773002, CC ECO:0000269|PubMed:12714658, ECO:0000269|PubMed:17932117}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF001947; AAC09069.1; -; mRNA. DR EMBL; AF016370; AAC51926.1; -; mRNA. DR EMBL; AK299980; BAG61801.1; -; mRNA. DR EMBL; AL611942; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53556.1; -; Genomic_DNA. DR EMBL; BC000184; AAH00184.1; -; mRNA. DR EMBL; BC001954; AAH01954.1; -; mRNA. DR CCDS; CCDS951.1; -. [O43395-1] DR PIR; T50839; T50839. DR PIR; T50840; T50840. DR RefSeq; NP_004689.1; NM_004698.2. [O43395-1] DR PDB; 1X4Q; NMR; -; A=1-79. DR PDB; 3JCR; EM; 7.00 A; K=1-683. DR PDB; 5O9Z; EM; 4.50 A; E=1-683. DR PDB; 6AH0; EM; 5.70 A; J=1-683. DR PDB; 6AHD; EM; 3.80 A; J=1-683. DR PDB; 6QW6; EM; 2.92 A; 4A=1-683. DR PDB; 6QX9; EM; 3.28 A; 4A=1-683. DR PDB; 7N2N; X-ray; 2.60 A; C=368-376. DR PDB; 7N2R; X-ray; 2.28 A; C=368-376. DR PDB; 7N2S; X-ray; 2.37 A; C=368-376. DR PDBsum; 1X4Q; -. DR PDBsum; 3JCR; -. DR PDBsum; 5O9Z; -. DR PDBsum; 6AH0; -. DR PDBsum; 6AHD; -. DR PDBsum; 6QW6; -. DR PDBsum; 6QX9; -. DR PDBsum; 7N2N; -. DR PDBsum; 7N2R; -. DR PDBsum; 7N2S; -. DR AlphaFoldDB; O43395; -. DR EMDB; EMD-3766; -. DR EMDB; EMD-4658; -. DR EMDB; EMD-4665; -. DR EMDB; EMD-9621; -. DR EMDB; EMD-9624; -. DR SMR; O43395; -. DR BioGRID; 114577; 259. DR CORUM; O43395; -. DR DIP; DIP-34508N; -. DR IntAct; O43395; 104. DR MINT; O43395; -. DR STRING; 9606.ENSP00000315379; -. DR GlyCosmos; O43395; 3 sites, 1 glycan. DR GlyGen; O43395; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; O43395; -. DR MetOSite; O43395; -. DR PhosphoSitePlus; O43395; -. DR SwissPalm; O43395; -. DR BioMuta; PRPF3; -. DR EPD; O43395; -. DR jPOST; O43395; -. DR MassIVE; O43395; -. DR MaxQB; O43395; -. DR PaxDb; 9606-ENSP00000315379; -. DR PeptideAtlas; O43395; -. DR ProteomicsDB; 48921; -. [O43395-1] DR ProteomicsDB; 5058; -. DR Pumba; O43395; -. DR Antibodypedia; 20281; 211 antibodies from 31 providers. DR DNASU; 9129; -. DR Ensembl; ENST00000324862.7; ENSP00000315379.6; ENSG00000117360.13. [O43395-1] DR GeneID; 9129; -. DR KEGG; hsa:9129; -. DR MANE-Select; ENST00000324862.7; ENSP00000315379.6; NM_004698.4; NP_004689.1. DR UCSC; uc001eum.5; human. [O43395-1] DR AGR; HGNC:17348; -. DR CTD; 9129; -. DR DisGeNET; 9129; -. DR GeneCards; PRPF3; -. DR GeneReviews; PRPF3; -. DR HGNC; HGNC:17348; PRPF3. DR HPA; ENSG00000117360; Low tissue specificity. DR MalaCards; PRPF3; -. DR MIM; 601414; phenotype. DR MIM; 607301; gene. DR neXtProt; NX_O43395; -. DR OpenTargets; ENSG00000117360; -. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA134892509; -. DR VEuPathDB; HostDB:ENSG00000117360; -. DR eggNOG; KOG2769; Eukaryota. DR GeneTree; ENSGT00390000011497; -. DR HOGENOM; CLU_015750_3_0_1; -. DR InParanoid; O43395; -. DR OMA; KNHEMRN; -. DR OrthoDB; 5489218at2759; -. DR PhylomeDB; O43395; -. DR TreeFam; TF313082; -. DR PathwayCommons; O43395; -. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR SignaLink; O43395; -. DR SIGNOR; O43395; -. DR BioGRID-ORCS; 9129; 672 hits in 1159 CRISPR screens. DR ChiTaRS; PRPF3; human. DR EvolutionaryTrace; O43395; -. DR GeneWiki; PRPF3; -. DR GenomeRNAi; 9129; -. DR Pharos; O43395; Tbio. DR PRO; PR:O43395; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O43395; Protein. DR Bgee; ENSG00000117360; Expressed in sural nerve and 202 other cell types or tissues. DR GO; GO:0015030; C:Cajal body; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005681; C:spliceosomal complex; NAS:UniProtKB. DR GO; GO:0071005; C:U2-type precatalytic spliceosome; IDA:UniProtKB. DR GO; GO:0046540; C:U4/U6 x U5 tri-snRNP complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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:UniProtKB. DR GO; GO:0008380; P:RNA splicing; TAS:ProtInc. DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; TAS:UniProtKB. DR GO; GO:0000244; P:spliceosomal tri-snRNP complex assembly; IDA:UniProtKB. DR Gene3D; 1.20.1390.10; PWI domain; 1. DR InterPro; IPR013881; Pre-mRNA_splic_Prp3_dom. DR InterPro; IPR027104; Prp3. DR InterPro; IPR010541; Prp3_C. DR InterPro; IPR002483; PWI_dom. DR InterPro; IPR036483; PWI_dom_sf. DR PANTHER; PTHR14212; U4/U6-ASSOCIATED RNA SPLICING FACTOR-RELATED; 1. DR PANTHER; PTHR14212:SF0; U4_U6 SMALL NUCLEAR RIBONUCLEOPROTEIN PRP3; 1. DR Pfam; PF08572; PRP3; 1. DR Pfam; PF06544; Prp3_C; 1. DR Pfam; PF01480; PWI; 1. DR SMART; SM00311; PWI; 1. DR SUPFAM; SSF101233; PWI domain; 1. DR PROSITE; PS51025; PWI; 1. DR Genevisible; O43395; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Isopeptide bond; mRNA processing; mRNA splicing; Nucleus; KW Phosphoprotein; Reference proteome; Retinitis pigmentosa; Spliceosome; KW Ubl conjugation. FT CHAIN 1..683 FT /note="U4/U6 small nuclear ribonucleoprotein Prp3" FT /id="PRO_0000097044" FT DOMAIN 1..87 FT /note="PWI" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00627" FT REGION 73..135 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 153..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 416..550 FT /note="Mediates interaction with SART3" FT /evidence="ECO:0000269|PubMed:15314151" FT COMPBIAS 73..122 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 164 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 167 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 619 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT CROSSLNK 139 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 244 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 252 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..135 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056265" FT VAR_SEQ 402..416 FT /note="TEENPKREDYFGITN -> GKSQERRLFWNHKSC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056266" FT VAR_SEQ 417..683 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056267" FT VARIANT 12 FT /note="K -> N (in dbSNP:rs12736964)" FT /id="VAR_051286" FT VARIANT 493 FT /note="P -> S (in RP18; dbSNP:rs121434242)" FT /evidence="ECO:0000269|PubMed:11773002" FT /id="VAR_046735" FT VARIANT 494 FT /note="T -> M (in RP18; reduces phosphorylation; impairs FT binding to PRPF4; impairs self-association; affects FT interaction with the U4/U5/U6 tri-snRNP complex; does not FT affect global pre-mRNA splicing; dbSNP:rs121434241)" FT /evidence="ECO:0000269|PubMed:11773002, FT ECO:0000269|PubMed:12714658, ECO:0000269|PubMed:17932117" FT /id="VAR_016877" FT CONFLICT 142 FT /note="I -> T (in Ref. 1; AAC09069)" FT /evidence="ECO:0000305" FT CONFLICT 273..274 FT /note="EL -> SV (in Ref. 1; AAC09069)" FT /evidence="ECO:0000305" FT HELIX 5..23 FT /evidence="ECO:0007829|PDB:1X4Q" FT HELIX 28..39 FT /evidence="ECO:0007829|PDB:1X4Q" FT HELIX 44..51 FT /evidence="ECO:0007829|PDB:1X4Q" FT TURN 52..55 FT /evidence="ECO:0007829|PDB:1X4Q" FT HELIX 56..58 FT /evidence="ECO:0007829|PDB:1X4Q" FT HELIX 60..73 FT /evidence="ECO:0007829|PDB:1X4Q" SQ SEQUENCE 683 AA; 77529 MW; 4AA6AA4C99110284 CRC64; MALSKRELDE LKPWIEKTVK RVLGFSEPTV VTAALNCVGK GMDKKKAADH LKPFLDDSTL RFVDKLFEAV EEGRSSRHSK SSSDRSRKRE LKEVFGDDSE ISKESSGVKK RRIPRFEEVE EEPEVIPGPP SESPGMLTKL QIKQMMEAAT RQIEERKKQL SFISPPTPQP KTPSSSQPER LPIGNTIQPS QAATFMNDAI EKARKAAELQ ARIQAQLALK PGLIGNANMV GLANLHAMGI APPKVELKDQ TKPTPLILDE QGRTVDATGK EIELTHRMPT LKANIRAVKR EQFKQQLKEK PSEDMESNTF FDPRVSIAPS QRQRRTFKFH DKGKFEKIAQ RLRTKAQLEK LQAEISQAAR KTGIHTSTRL ALIAPKKELK EGDIPEIEWW DSYIIPNGFD LTEENPKRED YFGITNLVEH PAQLNPPVDN DTPVTLGVYL TKKEQKKLRR QTRREAQKEL QEKVRLGLMP PPEPKVRISN LMRVLGTEAV QDPTKVEAHV RAQMAKRQKA HEEANAARKL TAEQRKVKKI KKLKEDISQG VHISVYRVRN LSNPAKKFKI EANAGQLYLT GVVVLHKDVN VVVVEGGPKA QKKFKRLMLH RIKWDEQTSN TKGDDDEESD EEAVKKTNKC VLVWEGTAKD RSFGEMKFKQ CPTENMAREH FKKHGAEHYW DLALSESVLE STD //