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FLASH GENE
Symbol FUS contributors: mct/pgu - updated : 20-04-2011
HGNC name fused in sarcoma
HGNC id 4010
Corresponding disease
ALS6 amyotrophic lateral sclerosis 6
AMLT1 acute myeloid leukemia
FUS myxoid and round cell subtype liposarcoma
Location 16p11.2      Physical location : 31.191.430 - 31.206.190
Synonym name
  • fusion (involved in t(12;16) in malignant liposarcoma)
  • fusion, derived from t(12;16) malignant liposarcoma
  • translocated in liposarcoma
  • heterogeneous nuclear ribonucleoprotein P2
  • FUS-CHOP fusion protein
  • 75 kDa DNA-pairing protein
  • fusion gene in myxoid liposarcoma
  • Synonym symbol(s) TLS, FUS-CHOP, FUS1, hnRNP-P2, POMp75, TLS/CHOP
    DNA
    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
    Physical map
    LOC115509 16p11.2 hypothetical protein BC014000 MGC3121 16p11.2 hypothetical protein MGC3121 FBS1 16p11.2 fibrosin 1 LOC388245 16 LOC388245 SRCAP 16p11.2 LOC388245 PHKG2 16p11.2-p12.1 phosphorylase kinase, gamma 2 (testis) LOC388246 16 LOC388246 RNF40 16p11.2-p11.1 ring finger protein 40 KIAA0326 16p11 ring finger protein 40 LOC390690 16 similar to Protein C20orf27 BCL7C 16p11 B-cell CLL/lymphoma 7C CTF1 16p11.2-p11.1 cardiotrophin 1 LOC283932 16p11.2 hypothetical protein LOC283932 MGC13024 16p11.2 hypothetical protein MGC13024 KIAA0339 16p11 hypothetical protein MGC13024 HSD3B7 16p11.2-12 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 STX1B2 16p12-p11 syntaxin 1B2 STX4A 16p13.13-p12.3 syntaxin 4A (placental) FLJ13479 16p11.2 hypothetical protein FLJ13479 KIAA0296 16p13.13-p13.2 hypothetical protein FLJ13479 IMAGE3455200 BCKDK 16p11.2 branched chain alpha-ketoacid dehydrogenase kinase MYST1 16p11.2 MYST histone acetyltransferase 1 PRSS8 16p11.2 protease, serine, 8 (prostasin) FLJ90661 16p11.2 hypothetical protein FLJ90661 LOC390691 16 similar to Filamin B (FLN-B) (Beta-filamin) (Actin-binding like protein) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) (ABP-280 homolog) (ABP-278) (Filamin 3) (Filamin homolog 1) (Fh1) FUS 16p11.2 fusion, derived from t(12;16) malignant liposarcoma ASC 16p12-p11.2 fusion, derived from t(12;16) malignant liposarcoma PYC1 16p11.2 pyrin-domain containing protein 1 ITGAM 16p11.2 integrin, alpha M (complement component receptor 3, alpha; also known as CD11b (p170), macrophage antigen alpha polypeptide) ITGAX 16p11.2 integrin, alpha X (antigen CD11C (p150), alpha polypeptide) COX6A2 16p12-p11 cytochrome c oxidase subunit VIa polypeptide 2 MGC46336 16p11.2 hypothetical protein MGC46336 FLJ13063 16p11.2 hypothetical protein FLJ13063 TGFB1I1 16p11 transforming growth factor beta 1 induced transcript 1 SLC5A2 16p11.2 solute carrier family 5 (sodium/glucose cotransporter), member 2 FLJ13868 16p11.2 hypothetical protein FLJ13868 ERAF 16p11.1 erythroid associated factor LOC388247 16 similar to cold shock domain protein A; Cold-shock domain protein A LOC342426 16p11.2 similar to zinc finger protein 267; zinc finger (C2H2) MGC3020 16p11.2 hypothetical protein MGC3020
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 5119 - 526 - 2009 19251627
    - - 5116 - 525 - -
    - - 5107 - 522 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    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
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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 PY nuclear localization signal (NLS) in the C-terminus of FUS is necessary for nuclear import (AAs 514-526)), and capable of binding DNA, RNA and splicing factors
  • HOMOLOGY
    intraspecies homolog to EWS1, highly
    Homologene
    FAMILY
  • RRM TET family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • 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)
  • 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
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FUS , AMLT1 , ALS6
    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
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    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