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   14-OCT-2015, entry version 121.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; 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.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   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.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   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
RT   project: 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
RT   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
RT   a dynamic nuclear and sarcomeric protein.";
RL   Differentiation 81:107-118(2011).
RN   [7]
RP   FUNCTION, OVEREXPRESSION, AND INTERACTION WITH SUV420H1.
RX   PubMed=23720823; DOI=10.1093/jmcb/mjt018;
RA   Neguembor M.V., Xynos A., Onorati M.C., Caccia R., Bortolanza S.,
RA   Godio C., 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
CC       a role in regulation of pre-mRNA splicing or in the assembly of
CC       rRNA into ribosomal subunits. May be involved in mRNA transport.
CC       May be involved in epigenetic regulation of muscle differentiation
CC       through regulation of activity of the histone-lysine N-
CC       methyltransferase SUV420H1. {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 SUV420H1 (via C-terminus).
CC       {ECO:0000250, ECO:0000269|PubMed:23720823}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, Cajal body {ECO:0000250}. Nucleus,
CC       nucleolus {ECO:0000250}. Cytoplasm. Cytoplasm, myofibril,
CC       sarcomere, Z line. Note=Localization changes during myogenesis
CC       from mainly cytoplasmic in undifferentiated myoblasts, to strongly
CC       nucleolar in early myotubes and back to cytoplasmic 5 days post-
CC       differentiation. Localized at the Z-line in the sarcomere of
CC       matured myotubes 8 days post-differentiation.
CC   -!- MISCELLANEOUS: Overexpression of Frg1 leads to development of
CC       facioscapulohumeral muscular dystrophy (FSHD1)-like symptoms such
CC       as kyphosis, progressive muscle dystrophy and skeletal muscle
CC       atrophy. It also causes aberrant pre-mRNA splicing of Tnnt3 and
CC       Mtmr1, affects the localization and activity of Suv420h1, and
CC       leads to increased levels of Eid3, resulting in inhibited muscle
CC       differentiation. These results suggest that human FSHD1 results
CC       from inappropriate overexpression of FRG1 which leads to abnormal
CC       alternative splicing of specific pre-mRNAs (PubMed:16341202,
CC       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   UniGene; Mm.217312; -.
DR   PDB; 2YUG; NMR; -; A=41-188.
DR   PDBsum; 2YUG; -.
DR   ProteinModelPortal; P97376; -.
DR   SMR; P97376; 41-188.
DR   BioGrid; 199743; 2.
DR   IntAct; P97376; 2.
DR   STRING; 10090.ENSMUSP00000033999; -.
DR   PhosphoSite; P97376; -.
DR   MaxQB; P97376; -.
DR   PaxDb; P97376; -.
DR   PRIDE; P97376; -.
DR   GeneID; 14300; -.
DR   KEGG; mmu:14300; -.
DR   UCSC; uc012gcs.1; mouse.
DR   CTD; 2483; -.
DR   MGI; MGI:893597; Frg1.
DR   eggNOG; NOG289849; -.
DR   HOGENOM; HOG000007130; -.
DR   HOVERGEN; HBG018564; -.
DR   InParanoid; P97376; -.
DR   KO; K13122; -.
DR   OMA; NSCFISY; -.
DR   OrthoDB; EOG7NKKMG; -.
DR   PhylomeDB; P97376; -.
DR   TreeFam; TF314108; -.
DR   EvolutionaryTrace; P97376; -.
DR   NextBio; 285717; -.
DR   PRO; PR:P97376; -.
DR   Proteomes; UP000000589; Unplaced.
DR   Bgee; P97376; -.
DR   CleanEx; MM_FRG1; -.
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; IEA:UniProtKB-SubCell.
DR   GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR   GO; GO:0044822; F:poly(A) RNA binding; ISO:MGI.
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_cross-linking.
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; Complete proteome; Cytoplasm;
KW   mRNA processing; mRNA splicing; Myogenesis; Nucleus;
KW   Reference proteome; Ribosome biogenesis; RNA-binding; rRNA processing;
KW   Spliceosome.
FT   CHAIN         1    258       Protein FRG1.
FT                                /FTId=PRO_0000220768.
FT   MOTIF        22     32       Nuclear localization signal.
FT                                {ECO:0000255}.
FT   MOTIF       235    251       Bipartite nuclear localization signal.
FT                                {ECO:0000255}.
FT   COMPBIAS      8     32       Lys-rich.
FT   CONFLICT    140    140       P -> Q (in Ref. 1; AAB39540).
FT                                {ECO:0000305}.
FT   STRAND       47     49       {ECO:0000244|PDB:2YUG}.
FT   HELIX        53     55       {ECO:0000244|PDB:2YUG}.
FT   STRAND       58     63       {ECO:0000244|PDB:2YUG}.
FT   STRAND       65     67       {ECO:0000244|PDB:2YUG}.
FT   STRAND       69     72       {ECO:0000244|PDB:2YUG}.
FT   STRAND       78     80       {ECO:0000244|PDB:2YUG}.
FT   STRAND       85     88       {ECO:0000244|PDB:2YUG}.
FT   TURN         93     95       {ECO:0000244|PDB:2YUG}.
FT   STRAND       97    101       {ECO:0000244|PDB:2YUG}.
FT   STRAND      103    105       {ECO:0000244|PDB:2YUG}.
FT   STRAND      107    111       {ECO:0000244|PDB:2YUG}.
FT   STRAND      116    119       {ECO:0000244|PDB:2YUG}.
FT   STRAND      121    127       {ECO:0000244|PDB:2YUG}.
FT   TURN        134    136       {ECO:0000244|PDB:2YUG}.
FT   STRAND      137    141       {ECO:0000244|PDB:2YUG}.
FT   STRAND      148    151       {ECO:0000244|PDB:2YUG}.
FT   STRAND      156    159       {ECO:0000244|PDB:2YUG}.
FT   STRAND      161    163       {ECO:0000244|PDB:2YUG}.
FT   STRAND      165    167       {ECO:0000244|PDB:2YUG}.
FT   TURN        174    176       {ECO:0000244|PDB:2YUG}.
FT   STRAND      179    182       {ECO:0000244|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
//