RBM20_MOUSE
ID RBM20_MOUSE Reviewed; 1199 AA.
AC Q3UQS8; E9PVK0; Q8CFS9;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=RNA-binding protein 20 {ECO:0000305};
DE AltName: Full=RNA-binding motif protein 20 {ECO:0000305};
GN Name=Rbm20 {ECO:0000303|PubMed:22466703, ECO:0000312|MGI:MGI:1920963};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-809.
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 629-1199 (ISOFORM 2).
RC TISSUE=Eye;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1026; SER-1049; SER-1054;
RP SER-1058; SER-1070; SER-1093 AND SER-1184, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22466703; DOI=10.1038/nm.2693;
RA Guo W., Schafer S., Greaser M.L., Radke M.H., Liss M., Govindarajan T.,
RA Maatz H., Schulz H., Li S., Parrish A.M., Dauksaite V., Vakeel P.,
RA Klaassen S., Gerull B., Thierfelder L., Regitz-Zagrosek V., Hacker T.A.,
RA Saupe K.W., Dec G.W., Ellinor P.T., MacRae C.A., Spallek B., Fischer R.,
RA Perrot A., Ozcelik C., Saar K., Hubner N., Gotthardt M.;
RT "RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.";
RL Nat. Med. 18:766-773(2012).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23886709; DOI=10.1016/j.febslet.2013.07.018;
RA Filippello A., Lorenzi P., Bergamo E., Romanelli M.G.;
RT "Identification of nuclear retention domains in the RBM20 protein.";
RL FEBS Lett. 587:2989-2995(2013).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=24584570; DOI=10.1093/hmg/ddu091;
RA Beraldi R., Li X., Martinez Fernandez A., Reyes S., Secreto F., Terzic A.,
RA Olson T.M., Nelson T.J.;
RT "Rbm20-deficient cardiogenesis reveals early disruption of RNA processing
RT and sarcomere remodeling establishing a developmental etiology for dilated
RT cardiomyopathy.";
RL Hum. Mol. Genet. 23:3779-3791(2014).
RN [8]
RP FUNCTION.
RX PubMed=27630136; DOI=10.1161/circulationaha.116.023003;
RA Methawasin M., Strom J.G., Slater R.E., Fernandez V., Saripalli C.,
RA Granzier H.;
RT "Experimentally increasing the compliance of titin through RNA binding
RT motif-20 (RBM20) inhibition improves diastolic function in a mouse model of
RT heart failure with preserved ejection fraction.";
RL Circulation 134:1085-1099(2016).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29650543; DOI=10.1161/circulationaha.117.031947;
RA van den Hoogenhof M.M.G., Beqqali A., Amin A.S., van der Made I.,
RA Aufiero S., Khan M.A.F., Schumacher C.A., Jansweijer J.A.,
RA van Spaendonck-Zwarts K.Y., Remme C.A., Backs J., Verkerk A.O.,
RA Baartscheer A., Pinto Y.M., Creemers E.E.;
RT "RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to
RT Disturbed Calcium Handling.";
RL Circulation 138:1330-1342(2018).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-637 AND SER-639, AND
RP MUTAGENESIS OF ARG-636; 637-SER--SER-639; SER-637 AND SER-639.
RX PubMed=29895960; DOI=10.1038/s41598-018-26624-w;
RA Murayama R., Kimura-Asami M., Togo-Ohno M., Yamasaki-Kato Y., Naruse T.K.,
RA Yamamoto T., Hayashi T., Ai T., Spoonamore K.G., Kovacs R.J., Vatta M.,
RA Iizuka M., Saito M., Wani S., Hiraoka Y., Kimura A., Kuroyanagi H.;
RT "Phosphorylation of the RSRSP stretch is critical for splicing regulation
RT by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization.";
RL Sci. Rep. 8:8970-8970(2018).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-637.
RX PubMed=33110103; DOI=10.1038/s41598-020-74800-8;
RA Ihara K., Sasano T., Hiraoka Y., Togo-Ohno M., Soejima Y., Sawabe M.,
RA Tsuchiya M., Ogawa H., Furukawa T., Kuroyanagi H.;
RT "A missense mutation in the RSRSP stretch of Rbm20 causes dilated
RT cardiomyopathy and atrial fibrillation in mice.";
RL Sci. Rep. 10:17894-17894(2020).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-637, AND MUTAGENESIS
RP OF SER-637.
RX PubMed=35394688; DOI=10.1096/fj.202101811rr;
RA Zhang Y., Wang C., Sun M., Jin Y., Braz C.U., Khatib H., Hacker T.A.,
RA Liss M., Gotthardt M., Granzier H., Ge Y., Guo W.;
RT "RBM20 phosphorylation and its role in nucleocytoplasmic transport and
RT cardiac pathogenesis.";
RL FASEB J. 36:e22302-e22302(2022).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-639.
RX PubMed=35041844; DOI=10.1016/j.yjmcc.2022.01.004;
RA Wang C., Zhang Y., Methawasin M., Braz C.U., Gao-Hu J., Yang B., Strom J.,
RA Gohlke J., Hacker T., Khatib H., Granzier H., Guo W.;
RT "RBM20S639G mutation is a high genetic risk factor for premature death
RT through RNA-protein condensates.";
RL J. Mol. Cell. Cardiol. 165:115-129(2022).
RN [14] {ECO:0007744|PDB:6SO9, ECO:0007744|PDB:6SOE}
RP STRUCTURE BY NMR OF 513-621 IN COMPLEX WITH RNA, FUNCTION, AND MUTAGENESIS
RP OF HIS-523; ASN-526; VAL-537; GLN-558; PHE-560; GLN-577; ARG-591; ARG-595
RP AND TYR-596.
RX PubMed=32187365; DOI=10.1093/nar/gkaa168;
RA Upadhyay S.K., Mackereth C.D.;
RT "Structural basis of UCUU RNA motif recognition by splicing factor RBM20.";
RL Nucleic Acids Res. 48:4538-4550(2020).
CC -!- FUNCTION: RNA-binding protein that acts as a regulator of mRNA splicing
CC of a subset of genes encoding key structural proteins involved in
CC cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH
CC (PubMed:22466703, PubMed:24584570, PubMed:27630136, PubMed:29650543,
CC PubMed:29895960, PubMed:33110103, PubMed:35394688, PubMed:35041844).
CC Acts as a repressor of mRNA splicing: specifically binds the 5'UCUU-3'
CC motif that is predominantly found within intronic sequences of pre-
CC mRNAs, leading to the exclusion of specific exons in target transcripts
CC (PubMed:32187365). RBM20-mediated exon skipping is hormone-dependent
CC and is essential for TTN isoform transition in both cardiac and
CC skeletal muscles (PubMed:27630136, PubMed:29895960, PubMed:33110103,
CC PubMed:35041844). RBM20-mediated exon skipping of TTN provides
CC substrates for the formation of circular RNA (circRNAs) from the TTN
CC transcripts (By similarity). Together with RBM24, promotes the
CC expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By
CC similarity). {ECO:0000250|UniProtKB:E9PT37,
CC ECO:0000250|UniProtKB:Q5T481, ECO:0000269|PubMed:22466703,
CC ECO:0000269|PubMed:24584570, ECO:0000269|PubMed:27630136,
CC ECO:0000269|PubMed:29650543, ECO:0000269|PubMed:29895960,
CC ECO:0000269|PubMed:32187365, ECO:0000269|PubMed:33110103,
CC ECO:0000269|PubMed:35041844, ECO:0000269|PubMed:35394688}.
CC -!- SUBUNIT: Associates with components of the U1 and U2 U1 small nuclear
CC ribonucleoprotein complexes. {ECO:0000250|UniProtKB:Q5T481}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22466703,
CC ECO:0000269|PubMed:23886709, ECO:0000269|PubMed:29895960,
CC ECO:0000269|PubMed:33110103, ECO:0000269|PubMed:35041844,
CC ECO:0000269|PubMed:35394688}. Cytoplasm, Cytoplasmic ribonucleoprotein
CC granule {ECO:0000269|PubMed:35041844, ECO:0000269|PubMed:35394688}.
CC Note=The active form that regulates alternative splicing localizes to
CC the nucleus (PubMed:35394688). Also localizes to cytoplasmic
CC ribonucleoprotein granules; localization to cytoplasmic
CC ribonucleoprotein granules plays an important regulatory role
CC (PubMed:35394688). Subcellular localization is regulated by
CC phosphorylation of different parts of the protein: while
CC phosphorylation of the RS (arginine/serine-rich) region promotes
CC nuclear localization, phosphorylation of the C-terminal disordered
CC region promotes localization to cytoplasmic ribonucleoprotein granules
CC (PubMed:29895960, PubMed:35394688). {ECO:0000269|PubMed:29895960,
CC ECO:0000269|PubMed:35394688}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UQS8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UQS8-2; Sequence=VSP_044393;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in striated muscle, with
CC highest expression in the heart (PubMed:22466703, PubMed:23886709). In
CC differentiating myoblasts, expression correlates with sarcomere
CC assembly: expression peaks when alpha-actinin is localized mainly in
CC mature Z bodies within the nascent myofiber and expression declines as
CC the sarcomeres continue to mature (PubMed:22466703). Also expressed in
CC kidney (PubMed:23886709). {ECO:0000269|PubMed:22466703,
CC ECO:0000269|PubMed:23886709}.
CC -!- INDUCTION: During early embryonic cardiogenesis.
CC {ECO:0000269|PubMed:24584570}.
CC -!- PTM: Phosphorylation regulates the subcellular localization.
CC Phosphorylation of Ser-637 and Ser-639 in the RS (arginine/serine-rich)
CC region promotes nuclear localization of the protein (PubMed:29895960,
CC PubMed:35394688). In contrast, phosphorylation of the C-terminal
CC disordered region promotes localization to cytoplasmic
CC ribonucleoprotein granules (By similarity).
CC {ECO:0000250|UniProtKB:Q5T481, ECO:0000269|PubMed:29895960,
CC ECO:0000269|PubMed:35394688}.
CC -!- DISRUPTION PHENOTYPE: Mice were born in normal Mendelian ratios, are
CC viable, and do not exhibit any visible phenotype (PubMed:29650543).
CC They however develop cardiomyopathy and display splicing defects in
CC genes related to calcium handling such as CAMK2D or RYR2
CC (PubMed:29650543). {ECO:0000269|PubMed:29650543}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH38663.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC117805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC121510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK142175; BAE24961.1; -; mRNA.
DR EMBL; BC038663; AAH38663.1; ALT_INIT; mRNA.
DR CCDS; CCDS50468.1; -. [Q3UQS8-1]
DR RefSeq; NP_001164318.1; NM_001170847.1. [Q3UQS8-1]
DR PDB; 6SO9; NMR; -; A=513-621.
DR PDB; 6SOE; NMR; -; A=513-621.
DR PDBsum; 6SO9; -.
DR PDBsum; 6SOE; -.
DR AlphaFoldDB; Q3UQS8; -.
DR SMR; Q3UQS8; -.
DR BioGRID; 216206; 1.
DR STRING; 10090.ENSMUSP00000129447; -.
DR iPTMnet; Q3UQS8; -.
DR PhosphoSitePlus; Q3UQS8; -.
DR MaxQB; Q3UQS8; -.
DR PaxDb; Q3UQS8; -.
DR PRIDE; Q3UQS8; -.
DR ProteomicsDB; 300259; -. [Q3UQS8-1]
DR ProteomicsDB; 300260; -. [Q3UQS8-2]
DR Antibodypedia; 50051; 100 antibodies from 21 providers.
DR DNASU; 73713; -.
DR Ensembl; ENSMUST00000164202; ENSMUSP00000129447; ENSMUSG00000043639. [Q3UQS8-1]
DR GeneID; 73713; -.
DR KEGG; mmu:73713; -.
DR UCSC; uc008hwz.2; mouse. [Q3UQS8-1]
DR CTD; 282996; -.
DR MGI; MGI:1920963; Rbm20.
DR VEuPathDB; HostDB:ENSMUSG00000043639; -.
DR eggNOG; ENOG502QW62; Eukaryota.
DR GeneTree; ENSGT01030000234642; -.
DR InParanoid; Q3UQS8; -.
DR OMA; HPFSGVM; -.
DR OrthoDB; 1545178at2759; -.
DR PhylomeDB; Q3UQS8; -.
DR TreeFam; TF333921; -.
DR BioGRID-ORCS; 73713; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Rbm20; mouse.
DR PRO; PR:Q3UQS8; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q3UQS8; protein.
DR Bgee; ENSMUSG00000043639; Expressed in interventricular septum and 158 other tissues.
DR ExpressionAtlas; Q3UQS8; baseline and differential.
DR Genevisible; Q3UQS8; MM.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:1990935; F:splicing factor binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007507; P:heart development; ISO:MGI.
DR GO; GO:0060914; P:heart formation; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IBA:GO_Central.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd12685; RRM_RBM20; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR000690; Matrin/U1-C_Znf_C2H2.
DR InterPro; IPR003604; Matrin/U1-like-C_Znf_C2H2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR034791; RBM20.
DR InterPro; IPR034790; RBM20_RRM.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR15592:SF11; PTHR15592:SF11; 1.
DR SMART; SM00360; RRM; 1.
DR SMART; SM00451; ZnF_U1; 2.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50171; ZF_MATRIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Metal-binding;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..1199
FT /note="RNA-binding protein 20"
FT /id="PRO_0000328825"
FT DOMAIN 520..595
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 410..444
FT /note="U1-type"
FT /evidence="ECO:0000255"
FT ZN_FING 1133..1164
FT /note="Matrin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00130"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..649
FT /note="RS"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT REGION 720..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 944..1077
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1172..1199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..55
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..186
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..685
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 739..835
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 857..872
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1018..1033
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1036..1058
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29895960,
FT ECO:0000269|PubMed:35394688"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29895960"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 644
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 787
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 871
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 1026
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1038
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 1049
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1054
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1070
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1088
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 1093
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 1184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1079..1199
FT /note="ENPRYMEVKSLNVRSPEFTEAELKEPLSLPSWEPEVFSELSIPLGVEFVVPR
FT TGFYCKLCGLFYTSEEAAKVSHCRSTVHYRNLQKYLSQLAEEGLKETEGTDSPSPERGG
FT IGPHLERKKL -> GSDSGAGLIPETPYWRKPQVHGSEISEREIARIHRSGAERAPFFA
FT FLGTGGVQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044393"
FT MUTAGEN 523
FT /note="H->A: Strongly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 526
FT /note="N->A: Slightly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 537
FT /note="V->I: Slightly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 558
FT /note="Q->A: Does not affect pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 560
FT /note="F->A: Strongly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 577
FT /note="Q->A: Does not affect pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 591
FT /note="R->M: Slightly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 595
FT /note="R->M: Strongly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 596
FT /note="Y->A: Strongly reduced pre-mRNA-binding."
FT /evidence="ECO:0000269|PubMed:32187365"
FT MUTAGEN 636
FT /note="R->W: Impaired ability to regulate alternative
FT splicing of Ttn (Titin) mRNAs."
FT /evidence="ECO:0000269|PubMed:29895960"
FT MUTAGEN 637..639
FT /note="SRS->ARA: Abolished localization to the nucleus,
FT leading to impaired ability to regulate alternative
FT splicing of Ttn (Titin) mRNAs."
FT /evidence="ECO:0000269|PubMed:29895960"
FT MUTAGEN 637
FT /note="S->A: Knockin mice show severe cardiac phenotypes,
FT characterized by dilated cardiomyopathy and atrial
FT fibrillation. Decreased localization to the nucleus,
FT leading to impaired ability to regulate alternative
FT splicing of Ttn (Titin) mRNAs."
FT /evidence="ECO:0000269|PubMed:29895960,
FT ECO:0000269|PubMed:33110103, ECO:0000269|PubMed:35394688"
FT MUTAGEN 639
FT /note="S->A: Decreased localization to the nucleus, leading
FT to impaired ability to regulate alternative splicing of Ttn
FT (Titin) mRNAs."
FT /evidence="ECO:0000269|PubMed:29895960"
FT MUTAGEN 639
FT /note="S->G: Knockin mice show severe cardiac phenotypes,
FT characterized by dilated cardiomyopathy, leading to
FT premature death. Decreased localization to the nucleus
FT associated with an increased localization to cytoplasmic
FT ribonucleoprotein granules."
FT /evidence="ECO:0000269|PubMed:35041844"
FT CONFLICT 77
FT /note="Q -> K (in Ref. 2; BAE24961)"
FT /evidence="ECO:0000305"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:6SO9"
FT STRAND 522..525
FT /evidence="ECO:0007829|PDB:6SO9"
FT TURN 529..531
FT /evidence="ECO:0007829|PDB:6SOE"
FT HELIX 534..544
FT /evidence="ECO:0007829|PDB:6SO9"
FT STRAND 547..553
FT /evidence="ECO:0007829|PDB:6SO9"
FT TURN 554..557
FT /evidence="ECO:0007829|PDB:6SO9"
FT STRAND 558..565
FT /evidence="ECO:0007829|PDB:6SO9"
FT HELIX 566..578
FT /evidence="ECO:0007829|PDB:6SO9"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:6SO9"
FT STRAND 586..592
FT /evidence="ECO:0007829|PDB:6SO9"
FT HELIX 608..617
FT /evidence="ECO:0007829|PDB:6SO9"
SQ SEQUENCE 1199 AA; 130124 MW; BBB9A371A2CD81BE CRC64;
MVLAVAMSQD ADPSGPEQPD RDACVMPGVQ GPSVPQGQQG MQPLPPPPPP QPQASLPQII
QNAAKLLDKS PFSVNNQNPL LTSPASVQLA QIQAQLTLHR LKMAQTAVTN NTAAATVLNQ
VLSKVAMSQP LFNQLRHPSV LGTAHGPTGV SQHAASVPSA HFPSTAIAFS PPSQTGGPGP
SVSLPSQPPN AMVVHTFSGV VPQTPAQPAV ILSLGKAGPT PATTGFYDYG KANSGQAYGS
ETEGQPGFLP ASASATASGS MTYEGHYSHT GQDGQPAFSK DFYGPNAQGP HIAGGFPADQ
TGSMKGDVGG LLQGTNSQWE RPPGFSGQNK PDITAGPSLW APPASQPYEL YDPEEPTSDR
APPAFGSRLN NSKQGFGCSC RRTKEGQAVL SVRPLQGHQL NDFRGLAPLH LPHICSICDK
KVFDLKDWEL HVKGKLHAQK CLLFSESAGL RSIRASGEGT LSASANSTAV YNPTGNEDYT
SNLGTSYAAI PTRAFAQSNP VFPSASSGTS FAAQRKGAGR VVHICNLPEG SCTENDVINL
GLPFGKVTNY ILMKSTNQAF LEMAYTEAAQ AMVQYYQEKP AIINGEKLLI RMSTRYKELQ
LKKPGKNVAA IIQDIHSQRE RDMLREADRY GPERPRSRSP MSRSLSPRSH SPPGPSRADW
GNGRDSYAWR DEDRETVPRR ENGEDKRDRL DVWAHDRKHY PRQLDKAELD ERLEGGRGYR
EKYLKSGSPG PLHSVSGYKG REDGYHRKEP KAKLDKYPKQ QPDVPGRSRR KEEARLREPR
HPHPEDSGKA EDLEPKITRA PDGTKSKQSE KSKTKRADRD QEGADDKKES QLAENEAGAE
EQEGMVGIQQ EGTESCDPEN TRTKKGQDCD SGSEPEGDNW YPTNMEELVT VDEVGEEDFI
MEPDLPELEE IVPIDQKDKT LPKICTCVTA TLGLDLAKDF TKQGETLGNG DAELSLKLPG
QVPSTSASCP NDTDLEMPGL NLDAERKPAE SETGLSLEVS NCYEKEARGE EDSDVSLAPA
VQQMSSPQPA DERARQSSPF LDDCKARGSP EDGSHEASPL EGKASPPTES DLQSQACREN
PRYMEVKSLN VRSPEFTEAE LKEPLSLPSW EPEVFSELSI PLGVEFVVPR TGFYCKLCGL
FYTSEEAAKV SHCRSTVHYR NLQKYLSQLA EEGLKETEGT DSPSPERGGI GPHLERKKL
