RBM20_PIG
ID RBM20_PIG Reviewed; 1223 AA.
AC P0DW16;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 1.
DT 03-AUG-2022, entry version 1.
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:33188278};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc;
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-636.
RX PubMed=33188278; DOI=10.1038/s41591-020-1087-x;
RG Wanek Program Preclinical Pipeline;
RA Schneider J.W., Oommen S., Qureshi M.Y., Goetsch S.C., Pease D.R.,
RA Sundsbak R.S., Guo W., Sun M., Sun H., Kuroyanagi H., Webster D.A.,
RA Coutts A.W., Holst K.A., Edwards B.S., Newville N., Hathcock M.A.,
RA Melkamu T., Briganti F., Wei W., Romanelli M.G., Fahrenkrug S.C.,
RA Frantz D.E., Olson T.M., Steinmetz L.M., Carlson D.F., Nelson T.J.;
RT "Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20
RT gene-edited pigs.";
RL Nat. Med. 26:1788-1800(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:33188278). Acts as a repressor of mRNA splicing: specifically
CC binds the 5'UCUU-3' motif that is predominantly found within intronic
CC sequences of pre-mRNAs, leading to the exclusion of specific exons in
CC target transcripts (By similarity). RBM20-mediated exon skipping is
CC hormone-dependent and is essential for TTN isoform transition in both
CC cardiac and skeletal muscles (By similarity). RBM20-mediated exon
CC skipping of TTN provides substrates for the formation of circular RNA
CC (circRNAs) from the TTN transcripts (By similarity). Together with
CC RBM24, promotes the expression of short isoforms of PDLIM5/ENH in
CC cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:E9PT37,
CC ECO:0000250|UniProtKB:Q5T481, ECO:0000269|PubMed:33188278}.
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:0000255|PROSITE-ProRule:PRU00130,
CC ECO:0000269|PubMed:33188278}. Cytoplasm, Cytoplasmic ribonucleoprotein
CC granule {ECO:0000269|PubMed:33188278}. Note=The active form that
CC regulates alternative splicing localizes to the nucleus
CC (PubMed:33188278). Also localizes to cytoplasmic ribonucleoprotein
CC granules; localization to cytoplasmic ribonucleoprotein granules plays
CC an important regulatory role (PubMed:33188278). Subcellular
CC localization is regulated by phosphorylation of different parts of the
CC protein: while phosphorylation of the RS (arginine/serine-rich) region
CC promotes nuclear localization, 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:33188278}.
CC -!- PTM: Phosphorylation regulates the subcellular localization (By
CC similarity). Phosphorylation of Ser-637 and Ser-639 in the RS
CC (arginine/serine-rich) region promotes nuclear localization of the
CC protein (By similarity). In contrast, phosphorylation of the C-terminal
CC disordered region promotes localization to cytoplasmic
CC ribonucleoprotein granules (By similarity).
CC {ECO:0000250|UniProtKB:Q5T481}.
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DR Proteomes; UP000314985; Chromosome 14.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50171; ZF_MATRIN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; mRNA processing; mRNA splicing; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..1223
FT /note="RNA-binding protein 20"
FT /id="PRO_0000456216"
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 1157..1188
FT /note="Matrin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00130"
FT REGION 630..657
FT /note="RS"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UQS8"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UQS8"
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 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 872
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 887
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 889
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 973
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 976
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T481"
FT MOD_RES 1044
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UQS8"
FT MOD_RES 1111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MOD_RES 1116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UQS8"
FT MOD_RES 1206
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9PT37"
FT MUTAGEN 636
FT /note="R->S: Knockin pigs show severe cardiac phenotypes,
FT characterized by severe congenital dilated cardiomyopathy
FT with advanced congestive heart failure and high mortality.
FT Decreased localization to the nucleus associated with an
FT increased localization to cytoplasmic ribonucleoprotein
FT granules."
FT /evidence="ECO:0000269|PubMed:33188278"
SQ SEQUENCE 1223 AA; 133295 MW; EFCBD7AFAD9D7E1D CRC64;
MVLAAAMSQD AEPSGPEQPD RDARSVPGAP APPAPPGPRG MQPPPPPPPP PPPPPQAGLP
QIIQNAAKLL DKTPFSVSNP NPLLPSPASL QLAQLQAQLT LHRLKLAQTA VTNNTAAATV
LNQVLSKVAM SQPLFNQLRH PSMISAPHGH TGVPPHATTV PSTRFPSNAI TFSAGQTRGP
GPSVNLPSQP PNTMVMHPFS GVMPQTPAQP AVILGIGKTG PAPAAAGFYE YGKATSGQAY
GSETDSQPSF LPASASTSGS VTYEGHYSHS GQDSQAAFPK DFYGPTSQGS QVAGTFAADT
AGGLKGEVGP LLQGPNSQWE SPHGFSGQSK PDLTAAPNLW PPHPSQPYEL YDPEEPTPDR
TPPSLGGRLN HSKQGFSGAR RRAKEEQAVL SMRPLQVQEL NDFHGVAPLH LPHICSICDK
KVFDLKDWEL HVKGKLHAQK CLLFSENTGV RCVLGPAEGT LCASPNSTAV YNPAGNEDYA
SNLGTSYAAL PARTFTQSNP AFPSASPGMN FVQRKLGAGR VVHICNLPEG SCTENDVINL
GLPFGKVTNY ILMKSTNQAF LEMAYTEAAQ AMVQYYQEKS AMINGEKLLI RMSKRYKELQ
LKKPGKTVAA IIQDIHSQRE RDMFREADRY GPERPRSRSP VSRSLSPRSH TPSFTSCSSS
HSPPGPSRAD WGNGRDSWEH SPYARREEER GPAPWRENGE DKRDRTDMWA HDRKHYPRQV
DKTELDERLE GGRGYREKHP RSGSPSSLHS VSGYKSREDG YYRKEPKGKS DKYLKQQQEA
PGRSRRKDEA RLRDGRHPYP DDSGKEDGLE AKGTKSKQSE KNRTKRPDRD QEGADDRKES
RMAESEAGKE EQDSMEESPS SVGRQEKETE SSDAENTRTR KEQDSESGSE AEGESWYPTN
MEELVTVDEV GEEEDFIMEP DIPELEEIVP IDQKDKICPE ICPCVTTTLE LDLAQDFTKE
GVKTIGNGAT EISLKSPKEP PSASTSCPSD MDVEMPGLNL DAERKPAECE TGLSLEGSGC
YEQQAKGAES SDVCLAPMLE QMSSPKPAEE RAWQPGPFLD DGKVGGTPED GAAEGRPLEE
KASTPTETDL QSQACQGVST QENSGYVEMK SLDARSPEYT EVELKQPLSL PSWEPEDVFS
ELSIPLGVEF VVPRTGFYCK LCGLFYTSEE MAKMSHCRSA VHYRNLQKYL SQLAEEGLKE
TEGAGSPRPE DSGIVPHFER KKL
