FUS (fusion involved in t (12;16) in malignant liposarcoma)
2004-07-01 PA Pérez-Mancera , Isidro Sánchez-Garía AffiliationLaboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain
Identity
HGNC
LOCATION
16p11.2
LOCUSID
ALIAS
ALS6,ETM4,FUS1,HNRNPP2,POMP75,TLS,altFUS
FUSION GENES
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
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.
Entity name
t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/ATF-1.
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
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
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8921363 | 1996 | Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. | Aman P et al |
| 1283316 | 1992 | Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). | Aman P et al |
| 7585257 | 1995 | Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry. | Calvio C et al |
| 8510758 | 1993 | Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. | Crozat A et al |
| 10655065 | 2000 | Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. | Hicks GG et al |
| 10523652 | 1999 | Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS). | Ichikawa H et al |
| 7805034 | 1995 | Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis. | Knight JC et al |
| 9242552 | 1997 | Consistent 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 |
| 10654943 | 2000 | Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. | Kuroda M et al |
| 9795213 | 1998 | Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes. | Morohoshi F et al |
| 17344859 | 2007 | Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. | Mullighan CG et al |
| 11896599 | 2002 | Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice. | Pérez-Mancera PA et al |
| 15139001 | 2004 | The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma. | Panagopoulos I et al |
| 9687511 | 1998 | TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis. | Perrotti D et al |
| 7970732 | 1994 | TLS/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 |
| 7503811 | 1993 | Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. | Rabbitts TH et al |
| 8058726 | 1994 | Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities. | Sánchez-García I et al |
| 12915480 | 2003 | Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. | Storlazzi CT et al |
| 11063792 | 2000 | Genetic 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 |
| 9264461 | 1997 | TLS (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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37984605 | 2024 | Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1. | 0 |
| 38168093 | 2024 | Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions. | 0 |
| 38170217 | 2024 | Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs. | 0 |
| 38311174 | 2024 | RNA and the RNA-binding protein FUS act in concert to prevent TDP-43 spatial segregation. | 0 |
| 38458997 | 2024 | Post-translational modification sites are present in hydrophilic cavities of alpha-synuclein, tau, FUS, and TDP-43 fibrils: A molecular dynamics study. | 0 |
| 38461154 | 2024 | FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease. | 3 |
| 38499486 | 2024 | FUS reads histone H3K36me3 to regulate alternative polyadenylation. | 0 |
| 38542501 | 2024 | Cell-Type-Dependent Recruitment Dynamics of FUS Protein at Laser-Induced DNA Damage Sites. | 0 |
| 38593618 | 2024 | A dynamic regulatory switch for phase separation of FUS protein: Zinc ions and zinc finger domain. | 0 |
| 38632300 | 2024 | An aberrant fused in sarcoma liquid droplet of amyotrophic lateral sclerosis pathological variant, R495X, accelerates liquid-solid phase transition. | 0 |
| 38671504 | 2024 | Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development. | 0 |
| 38862967 | 2024 | Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS. | 0 |
| 37984605 | 2024 | Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1. | 0 |
| 38168093 | 2024 | Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions. | 0 |
| 38170217 | 2024 | Disruption 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/fus
