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Symbol FUS contributors: mct/pgu - updated : 20-04-2017
HGNC name fused in sarcoma
HGNC id 4010
TYPE functioning gene
STRUCTURE 11.65 kb     15 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure the promoter and N-terminal part of FUS/TLS is translocated to the C-terminal domain of various DNA-binding transcription factors conferring a strong transcriptional activation domain to the fusion proteins
MAPPING cloned Y linked N status confirmed
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
15 - 5119 - 526 - 2009 19251627
- - 5116 - 525 - 2009 19251627
- - 5107 - 522 - 2009 19251627
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestine  highly
Lymphoid/Immunelymph node   highly
Reproductivefemale systemovary  highly
 female systemuterus  highly
Urinarykidney   highly
cell lineage
cell lines
  • N terminal SER, TYR, GLU, GLY rich domain, with transcriptional activating properties
  • a RNA binding domain
  • C2-C2 finger motif in the central region
  • a non-classical proline/tyrosine–nuclear localization signal (PY-NLS) in the C-terminus, necessary for nuclear import (AAs 514-526), and capable of binding DNA, RNA and splicing factors , that bind the import-karyopherin, karyopherinbeta2 (TNPO1) in a RAN-sensitive manner
    intraspecies homolog to EWS1, highly
  • RRM TET family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
  • normally located predominantly in the nucleus but the mutant forms accumulated in the cytoplasm of neurons )
  • also present in the cytosol where they are involved in diverse aspects of RNA metabolism, regulating the spatiotemporal fate of mRNA, i.e. subcellular localization, translation or degradation (Lagier-tourenne 2010)
  • mutations in the C-terminus of FUS show neuronal cytoplasmic FUS-positive inclusions, whereas in healthy controls, FUS is predominantly nuclear (but cytosolic FUS may accumulate during ageing)
  • FUS is normally located in the nucleus but in ALS, it translocates to the cytoplasm and misfolds, forming inclusions
  • basic FUNCTION
  • regulator of BCR/ABL-mediated leukemogenesis
  • implicated in mRNA export and mRNA transport to neuronal dendrites
  • may play a role in maintenance of genomic integrity
  • nucleoprotein that functions in DNA and RNA metabolism and implicated in tumorigenesis
  • sequestration of FUS to polyQ aggregates may play a role in diverse pathological changes in the brains of patients with polyQ disease
  • fusion protein caused by chromosomal translocations in human cancers
  • with TARDBP may play roles in micro-RNA (miRNA) processing
  • TARDBP and FUS implicated in neurodegeneration through errors in multiple steps of RNA processing
  • with TARDBP operate together in a common biochemical pathway
  • TARDBP and FUS are both RNA/DNA-binding proteins with striking structural and functional similarities
  • regulates expression of specific target genes, likely via recognition of specific single-stranded DNA sequences located within their promoter regions
  • is an unusual transcriptional regulator with the potential to activate or repress target genes via specific ssDNA sequences
  • may negatively regulate cell-cycle progression both through repressing transcription of RAS family genes and through alternative splicing that produces isoforms that delay cell-cycle progression
  • role in regulating processes as diverse as transcription, cell-cycle progress, DNA repair and genomic stability, and neurodegeneration
    a component
    RNA RNA binding protein (FUSIP/TASR1, SFRS2/SR351)
    small molecule other,
  • associated with neuronal intranuclear inclusions of Huntington disease brain
  • protein
  • interacting with serine arginine proteins involved in RNA splicing
  • interacts with several nuclear hormone receptors and with gene-specific transcription factors such as Spi-1/PU.1 or NF-KB
  • plays a significant role in expression of a number of RNAP II transcribed genes
  • FUS/TLS was found associated with TARDBP, association that is strongly enhanced by ALS-linked mutations
  • interaction between the FUS N-terminal and the cytolinker plectin (PLEC is important for normal FUS localization and function)
  • strong binding to the INTS3 gene
  • MAPT mRNA is a physiological splicing target of FUS
  • FUS bind the import-karyopherin, karyopherinbeta2 (TNPO1) in a RAN-sensitive manner, and TNPO1 plays likely a major role in nuclear localization of FUS
  • ATXN2 associates preferentially with pathological forms of FUS
  • interactions between FUS and proteins involved in neurodegenerative diseases and/or ubiquitin proteasome pathway, such as VCP, SFPQ, UBA1, and 26S proteosome non-ATPase regulatory subunit 12 (PSMD12)
  • FUS interacts with a mitochondrial chaperonin, HSPD1, and FUS translocation to mitochondria is, at least in part, mediated by HSPD1
  • FUS co-localises with the mitochondrial tethering protein Syntaphilin (SNPH), and mutations in FUS affect this relationship
  • cell & other
    corresponding disease(s) FUS , AMLT1 , ALS6 , ETM4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    rearranged in myxoid liposarcoma with translocation t(12;16) and in myeloid leukemia with translocation t(16;21)(q13;p11)
    tumoral fusion      
    fused with ATF1 in t (12;16)(q13;p11) in angiomatoid fibrous histiocytomas and with DDIT3 in myxoid liposarcoma
    tumoral fusion      
    fused with ERG in t(16;21)(p11;q22)in Ewing sarcoma
    tumoral fusion      
    with CREB3L2 in t(7;16) (q33;p11 in fibromyxoid sarcoma, low-grade
    constitutional germinal mutation      
    in ALS6, amyotrophic lateral sclerosis (R521G missense mutation in FUS/TLS led to aberrant trafficking with subsequent cytoplasmic retention of the mutant protein)
    tumoral     --over  
    in liposarcoma
    Susceptibility to essential tremor
    Variant & Polymorphism other
  • nonsense mutation (c.868C>T) associated to essential tremor
  • Candidate gene
    Therapy target
    major components of nuclear polyQ aggregate-interacting proteins in a Huntington disease cell model and was also associated with neuronal intranuclear inclusions of R6/2 mice