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 27-MAR-2024, entry version 187. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 117. DR IntAct; P56959; 61. DR MINT; P56959; -. DR STRING; 10090.ENSMUSP00000101858; -. DR GlyGen; P56959; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P56959; -. DR PhosphoSitePlus; P56959; -. DR SwissPalm; P56959; -. DR EPD; P56959; -. DR jPOST; P56959; -. DR PaxDb; 10090-ENSMUSP00000101858; -. DR PeptideAtlas; P56959; -. DR ProteomicsDB; 273014; -. DR Pumba; P56959; -. DR Antibodypedia; 1307; 542 antibodies from 38 providers. DR DNASU; 233908; -. DR Ensembl; ENSMUST00000106251.10; ENSMUSP00000101858.4; ENSMUSG00000030795.19. DR GeneID; 233908; -. DR KEGG; mmu:233908; -. DR UCSC; uc009jxo.1; mouse. DR AGR; MGI:1353633; -. 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; SYSKGPM; -. DR OrthoDB; 162112at2759; -. DR PhylomeDB; P56959; -. DR TreeFam; TF322599; -. DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway. DR Reactome; R-MMU-72203; Processing of Capped Intron-Containing Pre-mRNA. DR BioGRID-ORCS; 233908; 9 hits in 85 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 277 other cell types or tissues. DR ExpressionAtlas; P56959; baseline and differential. 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:0043232; C:intracellular non-membrane-bounded organelle; 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: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:0140693; F:molecular condensate scaffold activity; ISO:MGI. 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:1990000; P:amyloid fibril formation; ISO:MGI. 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:0006355; P:regulation of DNA-templated transcription; 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:0008380; P:RNA splicing; IMP:MGI. DR CDD; cd12535; RRM_FUS_TAF15; 1. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 4.10.1060.10; Zinc finger, RanBP2-type; 1. 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; RNA BINDING PROTEIN; 1. DR PANTHER; PTHR23238:SF5; RNA-BINDING PROTEIN FUS; 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; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS50102; RRM; 1. DR PROSITE; PS01358; ZF_RANBP2_1; 1. DR PROSITE; PS50199; ZF_RANBP2_2; 1. DR Genevisible; P56959; MM. 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 //