FRG1_MOUSE
ID FRG1_MOUSE Reviewed; 258 AA.
AC P97376; Q99M42;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Protein FRG1;
DE AltName: Full=FSHD region gene 1 protein;
GN Name=Frg1;
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 [MRNA].
RC STRAIN=NIH Swiss;
RX PubMed=9714712; DOI=10.1016/s0378-1119(98)00334-5;
RA Grewal P.K., Todd L.C., van der Maarel S., Frants R.R., Hewitt J.E.;
RT "FRG1, a gene in the FSH muscular dystrophy region on human chromosome
RT 4q35, is highly conserved in vertebrates and invertebrates.";
RL Gene 216:13-19(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Urinary bladder;
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].
RC TISSUE=Mammary tumor;
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 OVEREXPRESSION, AND SUBCELLULAR LOCATION.
RX PubMed=16341202; DOI=10.1038/nature04422;
RA Gabellini D., D'Antona G., Moggio M., Prelle A., Zecca C., Adami R.,
RA Angeletti B., Ciscato P., Pellegrino M.A., Bottinelli R., Green M.R.,
RA Tupler R.;
RT "Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1.";
RL Nature 439:973-977(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=20970242; DOI=10.1016/j.diff.2010.09.185;
RA Hanel M.L., Sun C.Y., Jones T.I., Long S.W., Zanotti S., Milner D.,
RA Jones P.L.;
RT "Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a
RT dynamic nuclear and sarcomeric protein.";
RL Differentiation 81:107-118(2011).
RN [7]
RP FUNCTION, OVEREXPRESSION, AND INTERACTION WITH KMT5B.
RX PubMed=23720823; DOI=10.1093/jmcb/mjt018;
RA Neguembor M.V., Xynos A., Onorati M.C., Caccia R., Bortolanza S., Godio C.,
RA Pistoni M., Corona D.F., Schotta G., Gabellini D.;
RT "FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone
RT methyltransferase and impairs myogenesis.";
RL J. Mol. Cell Biol. 5:294-307(2013).
RN [8]
RP STRUCTURE BY NMR OF 41-188.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of mouse Frg1 protein.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: Binds to mRNA in a sequence-independent manner. May play a
CC role in regulation of pre-mRNA splicing or in the assembly of rRNA into
CC ribosomal subunits. May be involved in mRNA transport. May be involved
CC in epigenetic regulation of muscle differentiation through regulation
CC of activity of the histone-lysine N-methyltransferase KMT5B.
CC {ECO:0000269|PubMed:23720823}.
CC -!- SUBUNIT: Homodimer and homotetramer in solution. Identified in the
CC spliceosome C complex. Interacts (via N-terminus) with KPNA2 and
CC NXF1/TAP. Interacts with F-actin with a stoichiometry of 2:1 (By
CC similarity). Interacts with KMT5B (via C-terminus). Interacts with
CC GARIN3, SMN1 and PABPN1 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q14331, ECO:0000269|PubMed:23720823}.
CC -!- SUBCELLULAR LOCATION: Nucleus, Cajal body
CC {ECO:0000250|UniProtKB:Q14331}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:16341202, ECO:0000269|PubMed:20970242}. Cytoplasm
CC {ECO:0000269|PubMed:20970242}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:20970242}. Note=Localization changes during
CC myogenesis from mainly cytoplasmic in undifferentiated myoblasts, to
CC strongly nucleolar in early myotubes and back to cytoplasmic 5 days
CC post-differentiation. Localized at the Z-line in the sarcomere of
CC matured myotubes 8 days post-differentiation.
CC {ECO:0000269|PubMed:20970242}.
CC -!- MISCELLANEOUS: Overexpression of Frg1 leads to development of
CC facioscapulohumeral muscular dystrophy (FSHD1)-like symptoms such as
CC kyphosis, progressive muscle dystrophy and skeletal muscle atrophy. It
CC also causes aberrant pre-mRNA splicing of Tnnt3 and Mtmr1, affects the
CC localization and activity of KMT5B, and leads to increased levels of
CC Eid3, resulting in inhibited muscle differentiation. These results
CC suggest that human FSHD1 results from inappropriate overexpression of
CC FRG1 which leads to abnormal alternative splicing of specific pre-mRNAs
CC (PubMed:16341202, PubMed:23720823). {ECO:0000305|PubMed:16341202,
CC ECO:0000305|PubMed:23720823}.
CC -!- SIMILARITY: Belongs to the FRG1 family. {ECO:0000305}.
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DR EMBL; U62105; AAB39540.1; -; mRNA.
DR EMBL; AK079229; BAC37582.1; -; mRNA.
DR EMBL; BC002027; AAH02027.1; -; mRNA.
DR CCDS; CCDS22263.1; -.
DR RefSeq; NP_038550.2; NM_013522.3.
DR RefSeq; XP_017168059.1; XM_017312570.1.
DR PDB; 2YUG; NMR; -; A=41-188.
DR PDBsum; 2YUG; -.
DR AlphaFoldDB; P97376; -.
DR SMR; P97376; -.
DR BioGRID; 199743; 31.
DR IntAct; P97376; 3.
DR STRING; 10090.ENSMUSP00000033999; -.
DR iPTMnet; P97376; -.
DR PhosphoSitePlus; P97376; -.
DR EPD; P97376; -.
DR PaxDb; P97376; -.
DR PeptideAtlas; P97376; -.
DR PRIDE; P97376; -.
DR ProteomicsDB; 267409; -.
DR DNASU; 14300; -.
DR Ensembl; ENSMUST00000033999; ENSMUSP00000033999; ENSMUSG00000031590.
DR GeneID; 14300; -.
DR KEGG; mmu:14300; -.
DR UCSC; uc012gcs.1; mouse.
DR CTD; 2483; -.
DR MGI; MGI:893597; Frg1.
DR VEuPathDB; HostDB:ENSMUSG00000031590; -.
DR eggNOG; KOG3962; Eukaryota.
DR GeneTree; ENSGT00390000004552; -.
DR HOGENOM; CLU_094616_0_0_1; -.
DR InParanoid; P97376; -.
DR OMA; EQWEPIF; -.
DR OrthoDB; 1400930at2759; -.
DR PhylomeDB; P97376; -.
DR TreeFam; TF314108; -.
DR BioGRID-ORCS; 14300; 6 hits in 71 CRISPR screens.
DR ChiTaRS; Frg1; mouse.
DR EvolutionaryTrace; P97376; -.
DR PRO; PR:P97376; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P97376; protein.
DR Bgee; ENSMUSG00000031590; Expressed in floor plate of midbrain and 254 other tissues.
DR ExpressionAtlas; P97376; baseline and differential.
DR Genevisible; P97376; MM.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0055120; C:striated muscle dense body; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR InterPro; IPR008999; Actin-crosslinking.
DR InterPro; IPR010414; FRG1.
DR PANTHER; PTHR12928; PTHR12928; 1.
DR Pfam; PF06229; FRG1; 1.
DR SUPFAM; SSF50405; SSF50405; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Cytoplasm; mRNA processing; mRNA splicing;
KW Myogenesis; Nucleus; Reference proteome; Ribosome biogenesis; RNA-binding;
KW rRNA processing; Spliceosome.
FT CHAIN 1..258
FT /note="Protein FRG1"
FT /id="PRO_0000220768"
FT REGION 16..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 22..32
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 235..251
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT CONFLICT 140
FT /note="P -> Q (in Ref. 1; AAB39540)"
FT /evidence="ECO:0000305"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:2YUG"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:2YUG"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 121..127
FT /evidence="ECO:0007829|PDB:2YUG"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:2YUG"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:2YUG"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:2YUG"
SQ SEQUENCE 258 AA; 29127 MW; 1D0C07CF83897ACE CRC64;
MAEYSYVKST KLVLKGTKAK SKKKKSKDKK RKREEDEETQ LDIVGIWWTV SNFGEISGTI
AIEMDKGAYI HALDNGLFTL GAPHREVDEG PSPPEQFTAV KLSDSRIALK SGYGKYLGIN
SDGLVVGRSD AIGPREQWEP VFQDGKMALL ASNSCFIRCN EAGDIEAKNK TAGEEEMIKI
RSCAERETKK KDDIPEEDKG SVKQCEINYV KKFQSFQDHK LKISKEDSKI LKKARKDGFL
HETLLDRRAK LKADRYCK
