FUS (fusion involved in t (12;16) in malignant liposarcoma)

2004-07-01   PA Pérez-Mancera  , Isidro Sánchez-Garía  

Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain

Identity

HGNC
FUS
LOCATION
16p11.2
LOCUSID
2521
ALIAS
ALS6,ETM4,FUS1,HNRNPP2,POMP75,TLS,altFUS
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

The gene has 15 exons, and the total genomic sequence spanning the FUS gene is approx. 12 Kb.

Transcription

Transcript lenght: 1,9 Kb. There are two isoforms produced by an alternative splicing that involved the exon 4a (145 bp) or the exon 4b (142 bp).

Proteins

Atlas Image

Description

526 amino acids (isoform with the exon 4a) or 525 aa (isoform with the exon 4b), 68 Kda. The protein contains different domains:
  • a N-terminal SYQG-rich region;
  • a RGG-rich region;
  • a RNA binding domain;
  • a RGG-rich region;
  • a Cys2/Cys2-zinc finger motif and;
  • a C-terminal RGG-rich region.

    • Expression

    FUS is expressed in a housekeeping pattern.

    Localisation

    Nuclear, although FUS shuttles from the nucleus to the cytoplasm in a large complex that contains mRNA and hnRNPs.

    Function

    FUS is a RNA-binding protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. FUS seems to have a function as a heterogeneous ribonuclear protein (hnRNP)-like chaperone of RNA. In addition, it has been suggested that FUS might have a role in the BCR/ABL-mediated leukemogenesis.

    Homology

    FUS forms a sub-family of RNA binding proteins with EWS and RBP56/hTAFII68. FUS has homologous in mouse (fus), rat (pigpen) and Drosophila (Cabeza/SARFH).

    Mutations

    Germinal

    In the mouse, germline mutation in the fus gene produces male sterility, sensitivity to radiation, defective B-lymphocyte development and activation, chromosomal instability and perinatal death.

    Implicated in

    Note
    The FUS gene is implicated in several chromosomal translocations associated to both solid tumors and leukemias. The result of these chromosomal translocations are gene fusions. FUS contributes to these fusions with its N-terminal part, just before the RNA-binding domain. This domain confers to the fusion protein a transcriptional activation domain. These fusion genes generated as a result of chromosomal rearragements are used to monitor diagnosis and treatment.
    Atlas Image
    Entity name
    t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/ATF-1.
    Disease
    Angiomatoid fibrous histiocytoma (AFH).
    Hybrid gene
    FUS was interrupted at codon 175 (exon 5) and fused to codon 110 (exon 5) of ATF-1, resulting in an in-frame junction with a glycine to valine (GGT to GTT) transition.
    Entity name
    t(7;16)(q33;p11) chromosomal translocation. It produces the fusion protein FUS/CREB3L2 (also known as BBF2H7).
    Disease
    Low grade fibromyxoid sarcoma (LGFMS).
    Hybrid gene
    The breakpoints in the fusion transcripts are produced between the exons 6 or 7 of FUS and the exon 5 of CREB3L2.
    Entity name
    t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3 (also known as CHOP).
    Disease
    Myxoid liposarcoma (MLS).
    Hybrid gene
    9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3.
    Oncogenesis
    The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter.
    Entity name
    t(16;21)(p11;q22) chromosomal translocation. It produces the fusion protein FUS/ERG.
    Disease
    Acute myeloid leukemia (AML).
    Hybrid gene
    The junction of both genes is produced between the exons 6 or 7 of FUS and the exon 9 of ERG,or between the exon 8 of FUS and the exon 7 of ERG.

    Breakpoints

    Atlas Image

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    89213631996Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS.Aman P et al
    12833161992Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).Aman P et al
    75852571995Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry.Calvio C et al
    85107581993Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.Crozat A et al
    106550652000Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death.Hicks GG et al
    105236521999Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS).Ichikawa H et al
    78050341995Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.Knight JC et al
    92425521997Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.Kong XT et al
    106549432000Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.Kuroda M et al
    97952131998Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes.Morohoshi F et al
    173448592007Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.Mullighan CG et al
    118965992002Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.Pérez-Mancera PA et al
    151390012004The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.Panagopoulos I et al
    96875111998TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis.Perrotti D et al
    79707321994TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain.Prasad DD et al
    75038111993Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.Rabbitts TH et al
    80587261994Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities.Sánchez-García I et al
    129154802003Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma.Storlazzi CT et al
    110637922000Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.Waters BL et al
    92644611997TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling.Zinszner H et al

    Other Information

    Locus ID:

    NCBI: 2521
    MIM: 137070
    HGNC: 4010
    Ensembl: ENSG00000089280

    Variants:

    dbSNP: 2521
    ClinVar: 2521
    TCGA: ENSG00000089280
    COSMIC: FUS

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000089280ENST00000254108P35637
    ENSG00000089280ENST00000254108Q6IBQ5
    ENSG00000089280ENST00000380244P35637
    ENSG00000089280ENST00000566605H3BNZ4
    ENSG00000089280ENST00000568685H3BPE7

    Expression (GTEx)

    0
    50
    100
    150
    200
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Transcriptional misregulation in cancerKEGGko05202
    Transcriptional misregulation in cancerKEGGhsa05202
    Gene ExpressionREACTOMER-HSA-74160
    Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
    mRNA SplicingREACTOMER-HSA-72172
    mRNA Splicing - Major PathwayREACTOMER-HSA-72163

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    379846052024Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1.0
    381680932024Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.0
    381702172024Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs.0
    383111742024RNA and the RNA-binding protein FUS act in concert to prevent TDP-43 spatial segregation.0
    384589972024Post-translational modification sites are present in hydrophilic cavities of alpha-synuclein, tau, FUS, and TDP-43 fibrils: A molecular dynamics study.0
    384611542024FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.3
    384994862024FUS reads histone H3K36me3 to regulate alternative polyadenylation.0
    385425012024Cell-Type-Dependent Recruitment Dynamics of FUS Protein at Laser-Induced DNA Damage Sites.0
    385936182024A dynamic regulatory switch for phase separation of FUS protein: Zinc ions and zinc finger domain.0
    386323002024An aberrant fused in sarcoma liquid droplet of amyotrophic lateral sclerosis pathological variant, R495X, accelerates liquid-solid phase transition.0
    386715042024Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development.0
    388629672024Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.0
    379846052024Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1.0
    381680932024Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.0
    381702172024Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs.0

    Citation

    PA Pérez-Mancera ; Isidro Sánchez-Garía

    FUS (fusion involved in t (12;16) in malignant liposarcoma)

    Atlas Genet Cytogenet Oncol Haematol. 2004-07-01

    Online version: http://atlasgeneticsoncology.org/gene/44