FUS_MOUSE
ID FUS_MOUSE Reviewed; 518 AA.
AC P56959;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=RNA-binding protein FUS;
DE AltName: Full=Protein pigpen;
GN Name=Fus;
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].
RX PubMed=12950080; DOI=10.1002/dvdy.10353;
RA Alappat S.R., Zhang M., Zhao X., Alliegro M.A., Alliegro M.C.,
RA Burdsal C.A.;
RT "Mouse pigpen encodes a nuclear protein whose expression is developmentally
RT regulated during craniofacial morphogenesis.";
RL Dev. Dyn. 228:59-71(2003).
RN [2]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16317045; DOI=10.1242/jcs.02692;
RA Fujii R., Takumi T.;
RT "TLS facilitates transport of mRNA encoding an actin-stabilizing protein to
RT dendritic spines.";
RL J. Cell Sci. 118:5755-5765(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
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 [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-387 AND ARG-400, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [5]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=25968143; DOI=10.1038/ncomms8098;
RA Udagawa T., Fujioka Y., Tanaka M., Honda D., Yokoi S., Riku Y., Ibi D.,
RA Nagai T., Yamada K., Watanabe H., Katsuno M., Inada T., Ohno K., Sokabe M.,
RA Okado H., Ishigaki S., Sobue G.;
RT "FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via
RT GluA1 mRNA stabilization.";
RL Nat. Commun. 6:7098-7098(2015).
CC -!- FUNCTION: DNA/RNA-binding protein that plays a role in various cellular
CC processes such as transcription regulation, RNA splicing, RNA
CC transport, DNA repair and damage response. Binds to nascent pre-mRNAs
CC and acts as a molecular mediator between RNA polymerase II and U1 small
CC nuclear ribonucleoprotein thereby coupling transcription and splicing.
CC Binds also its own pre-mRNA and autoregulates its expression; this
CC autoregulation mechanism is mediated by non-sense-mediated decay. Plays
CC a role in DNA repair mechanisms by promoting D-loop formation and
CC homologous recombination during DNA double-strand break repair (By
CC similarity). In neuronal cells, plays crucial roles in dendritic spine
CC formation and stability, RNA transport, mRNA stability and synaptic
CC homeostasis (PubMed:16317045, PubMed:25968143).
CC {ECO:0000250|UniProtKB:P35637, ECO:0000269|PubMed:16317045,
CC ECO:0000269|PubMed:25968143}.
CC -!- SUBUNIT: Self-oligomerizes (via N-terminal region). Oligomerization is
CC essential for chromatin binding. Component of nuclear riboprotein
CC complexes. Interacts with ILF3, TDRD3 and SF1. Interacts through its C-
CC terminus with SFRS13A. Interacts with OTUB1 and SARNP. Interacts with
CC LRSAM1. Interacts with SAFB1 in a DNA-dependent manner; this
CC interaction tethers FUS to chromatin. Interacts with MATR3. Interacts
CC with SNRNP70 and POLR2A; these interactions couple RNA transcription
CC and splicing. Interacts (through its RNA-binding domain) with RALY
CC (through its RNA-binding domain); both are components of the same RNPs.
CC {ECO:0000250|UniProtKB:P35637}.
CC -!- INTERACTION:
CC P56959; P97801: Smn1; NbExp=4; IntAct=EBI-400452, EBI-309807;
CC P56959; Q6UWE0: LRSAM1; Xeno; NbExp=2; IntAct=EBI-400452, EBI-720984;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P35637}.
CC Note=Displays a punctate pattern inside the nucleus and is excluded
CC from nucleoli. {ECO:0000250|UniProtKB:P35637}.
CC -!- PTM: Phosphorylated in its N-terminal serine residues upon induced DNA
CC damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region.
CC {ECO:0000250|UniProtKB:P35637}.
CC -!- SIMILARITY: Belongs to the RRM TET family. {ECO:0000305}.
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DR EMBL; AF224264; AAF70602.1; -; mRNA.
DR CCDS; CCDS21886.1; -.
DR RefSeq; NP_631888.1; NM_139149.2.
DR AlphaFoldDB; P56959; -.
DR BMRB; P56959; -.
DR SMR; P56959; -.
DR BioGRID; 231475; 115.
DR IntAct; P56959; 61.
DR MINT; P56959; -.
DR STRING; 10090.ENSMUSP00000101858; -.
DR iPTMnet; P56959; -.
DR PhosphoSitePlus; P56959; -.
DR SwissPalm; P56959; -.
DR EPD; P56959; -.
DR jPOST; P56959; -.
DR PaxDb; P56959; -.
DR PeptideAtlas; P56959; -.
DR PRIDE; P56959; -.
DR ProteomicsDB; 273014; -.
DR Antibodypedia; 1307; 479 antibodies from 38 providers.
DR DNASU; 233908; -.
DR Ensembl; ENSMUST00000106251; ENSMUSP00000101858; ENSMUSG00000030795.
DR GeneID; 233908; -.
DR KEGG; mmu:233908; -.
DR UCSC; uc009jxo.1; mouse.
DR CTD; 2521; -.
DR MGI; MGI:1353633; Fus.
DR VEuPathDB; HostDB:ENSMUSG00000030795; -.
DR eggNOG; KOG1995; Eukaryota.
DR GeneTree; ENSGT00940000157290; -.
DR HOGENOM; CLU_025609_2_0_1; -.
DR InParanoid; P56959; -.
DR OMA; DSYNKGP; -.
DR OrthoDB; 1539664at2759; -.
DR PhylomeDB; P56959; -.
DR TreeFam; TF322599; -.
DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway.
DR BioGRID-ORCS; 233908; 9 hits in 80 CRISPR screens.
DR ChiTaRS; Fus; mouse.
DR PRO; PR:P56959; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P56959; protein.
DR Bgee; ENSMUSG00000030795; Expressed in somite and 274 other tissues.
DR ExpressionAtlas; P56959; baseline and differential.
DR Genevisible; P56959; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0044327; C:dendritic spine head; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005844; C:polysome; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:MGI.
DR GO; GO:0031489; F:myosin V binding; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISO:MGI.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0048255; P:mRNA stabilization; ISO:MGI.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR GO; GO:0043484; P:regulation of RNA splicing; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0008380; P:RNA splicing; IMP:MGI.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR034459; FUS.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR034870; TET_fam.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR PANTHER; PTHR23238; PTHR23238; 1.
DR PANTHER; PTHR23238:SF5; PTHR23238:SF5; 1.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF00641; zf-RanBP; 1.
DR SMART; SM00360; RRM; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Isopeptide bond; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Ubl conjugation;
KW Zinc; Zinc-finger.
FT CHAIN 1..518
FT /note="RNA-binding protein FUS"
FT /id="PRO_0000081592"
FT DOMAIN 278..364
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 415..446
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT REGION 1..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 437..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..484
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..518
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 217
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 217
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 219
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 219
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 235
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 237
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 241
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 244
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 252
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 370
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 376
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 379
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 381
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 387
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 400
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 400
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 466
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 468
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 473
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 477
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 479
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 483
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 487
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 490
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 495
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT MOD_RES 495
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35637"
FT CROSSLNK 327
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P35637"
SQ SEQUENCE 518 AA; 52673 MW; E06F231BFEED78D6 CRC64;
MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YGQSADTSGY GQSSYGSSYG
QTQNTGYGTQ SAPQGYGSTG GYGSSQSSQS SYGQQSSYPG YGQQPAPSST SGSYGGSSQS
SSYGQPQSGG YGQQSGYGGQ QQSYGQQQSS YNPPQGYGQQ NQYNSSSGGG GGGGGGNYGQ
DQSSMSGGGG GGGYGNQDQS GGGGGGYGGG QQDRGGRGRG GGGGYNRSSG GYEPRGRGGG
RGGRGGMGGS DRGGFNKFGG PRDQGSRHDS EQDNSDNNTI FVQGLGENVT IESVADYFKQ
IGIIKTNKKT GQPMINLYTD RETGKLKGEA TVSFDDPPSA KAAIDWFDGK EFSGNPIKVS
FATRRADFNR GGGNGRGGRG RGGPMGRGGY GGGGSGGGGR GGFPSGGGGG GGQQRAGDWK
CPNPTCENMN FSWRNECNQC KAPKPDGPGG GPGGSHMGGN YGDDRRGRGG YDRGGYRGRG
GDRGGFRGGR GGGDRGGFGP GKMDSRGEHR QDRRERPY
