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Protein

RNA-binding protein FUS

Gene

FUS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single-stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri422 – 453RanBP2-typePROSITE-ProRule annotationAdd BLAST32

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, RNA-binding
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-72163 mRNA Splicing - Major Pathway
SIGNORiP35637

Names & Taxonomyi

Protein namesi
Recommended name:
RNA-binding protein FUS
Alternative name(s):
75 kDa DNA-pairing protein
Oncogene FUS
Oncogene TLS
POMp75
Translocated in liposarcoma protein
Gene namesi
Name:FUS
Synonyms:TLS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000089280.18
HGNCiHGNC:4010 FUS
MIMi137070 gene
neXtProtiNX_P35637

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3.1 Publication
A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG.1 Publication
Angiomatoid fibrous histiocytoma (AFH)1 Publication
The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein.1 Publication
Disease descriptionA distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.
See also OMIM:612160
Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (ALS6)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
See also OMIM:608030
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068918191G → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs148758737Ensembl.1
Natural variantiVAR_068920225G → V in ALS6. 1 Publication1
Natural variantiVAR_068921230G → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs748374535Ensembl.1
Natural variantiVAR_068922234R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs777819849Ensembl.1
Natural variantiVAR_054837244R → C in ALS6. 1 Publication1
Natural variantiVAR_068924507G → D in ALS6. 1 PublicationCorresponds to variant dbSNP:rs267606831EnsemblClinVar.1
Natural variantiVAR_054838514R → G in ALS6. 1 Publication1
Natural variantiVAR_054839514R → S in ALS6. 1 Publication1
Natural variantiVAR_054840515G → C in ALS6. 1 Publication1
Natural variantiVAR_054842518R → K in ALS6. 1 PublicationCorresponds to variant dbSNP:rs121909669EnsemblClinVar.1
Natural variantiVAR_054843521R → C in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 3 PublicationsCorresponds to variant dbSNP:rs121909668EnsemblClinVar.1
Natural variantiVAR_054844521R → G in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 1 PublicationCorresponds to variant dbSNP:rs121909668EnsemblClinVar.1
Natural variantiVAR_054845521R → H in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 4 PublicationsCorresponds to variant dbSNP:rs121909671EnsemblClinVar.1
Natural variantiVAR_054846522R → G in ALS6. 1 Publication1
Natural variantiVAR_054847524R → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041389EnsemblClinVar.1
Natural variantiVAR_054848524R → T in ALS6. 1 Publication1
Natural variantiVAR_054849525P → L in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041390EnsemblClinVar.1
Natural variantiVAR_077328526Y → YY in ALS6; unknown pathological significance. 1 Publication1
Tremor, hereditary essential 4 (ETM4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant.
See also OMIM:614782
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068923431P → L in ETM4. 1 PublicationCorresponds to variant dbSNP:rs186547381EnsemblClinVar.1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei175Breakpoint for translocation to form chimeric FUS/ATF1 protein1
Sitei266 – 267Breakpoint for translocation to form FUS/TLS-CHOP oncogene2

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Neurodegeneration, Proto-oncogene

Organism-specific databases

DisGeNETi2521
GeneReviewsiFUS
MalaCardsiFUS
MIMi608030 phenotype
612160 phenotype
614782 phenotype
OpenTargetsiENSG00000089280
Orphaneti803 Amyotrophic lateral sclerosis
275872 Frontotemporal dementia with motor neuron disease
862 Hereditary essential tremor
300605 Juvenile amyotrophic lateral sclerosis
79105 Myxofibrosarcoma
99967 Myxoid/round cell liposarcoma
PharmGKBiPA28425

Polymorphism and mutation databases

BioMutaiFUS
DMDMi544357

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000815911 – 526RNA-binding protein FUSAdd BLAST526

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei216Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei216Omega-N-methylarginine; alternateCombined sources1
Modified residuei218Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei218Omega-N-methylarginine; alternateCombined sources1
Modified residuei221PhosphoserineCombined sources1
Modified residuei242Asymmetric dimethylarginine1 Publication1
Modified residuei244Asymmetric dimethylarginine1 Publication1
Modified residuei248Asymmetric dimethylarginine1 Publication1
Modified residuei251Asymmetric dimethylarginine1 Publication1
Modified residuei259Asymmetric dimethylarginine1 Publication1
Modified residuei277PhosphoserineCombined sources1
Modified residuei286PhosphothreonineCombined sources1
Cross-linki334Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei340PhosphoserineCombined sources1
Modified residuei377Asymmetric dimethylarginine1 Publication1
Modified residuei383Asymmetric dimethylarginine1 Publication1
Modified residuei386Asymmetric dimethylarginine1 Publication1
Modified residuei388Asymmetric dimethylarginine1 Publication1
Modified residuei394Asymmetric dimethylarginine1 Publication1
Modified residuei407Asymmetric dimethylarginine; alternate1 Publication1
Modified residuei407Omega-N-methylarginine; alternateBy similarity1
Modified residuei473Asymmetric dimethylarginine1 Publication1
Modified residuei476Asymmetric dimethylarginine1 Publication1
Modified residuei481Asymmetric dimethylarginine1 Publication1
Modified residuei485Asymmetric dimethylarginine1 Publication1
Modified residuei487Asymmetric dimethylarginine1 Publication1
Modified residuei491Asymmetric dimethylarginine1 Publication1
Modified residuei495Asymmetric dimethylarginine1 Publication1
Modified residuei498Asymmetric dimethylarginine1 Publication1
Modified residuei503Asymmetric dimethylarginine; alternate1 Publication1
Modified residuei503Omega-N-methylarginine; alternateCombined sources1

Post-translational modificationi

Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine.

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35637
PaxDbiP35637
PeptideAtlasiP35637
PRIDEiP35637
ProteomicsDBi55119
55120 [P35637-2]
TopDownProteomicsiP35637-1 [P35637-1]
P35637-2 [P35637-2]

PTM databases

iPTMnetiP35637
PhosphoSitePlusiP35637
SwissPalmiP35637

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000089280
CleanExiHS_FUS
ExpressionAtlasiP35637 baseline and differential
GenevisibleiP35637 HS

Organism-specific databases

HPAiCAB033036
CAB058691
HPA008784

Interactioni

Subunit structurei

Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1. Interacts through its C-terminus with SFRS13A. Interacts with OTUB1 and SARNP.Interacts with LRSAM1 (PubMed:27615052).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108797, 344 interactors
CORUMiP35637
DIPiDIP-29857N
IntActiP35637, 67 interactors
MINTiP35637
STRINGi9606.ENSP00000254108

Structurei

Secondary structure

1526
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 40Combined sources3
Beta strandi47 – 49Combined sources3
Beta strandi59 – 64Combined sources6
Beta strandi67 – 70Combined sources4
Beta strandi73 – 75Combined sources3
Beta strandi93 – 95Combined sources3
Beta strandi285 – 290Combined sources6
Helixi298 – 305Combined sources8
Turni306 – 308Combined sources3
Turni315 – 318Combined sources4
Beta strandi319 – 326Combined sources8
Turni328 – 330Combined sources3
Beta strandi332 – 343Combined sources12
Helixi344 – 354Combined sources11
Beta strandi358 – 363Combined sources6
Beta strandi365 – 368Combined sources4
Beta strandi379 – 381Combined sources3
Helixi514 – 521Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LA6NMR-A282-370[»]
2LCWNMR-A278-385[»]
4FDDX-ray2.30B498-526[»]
4FQ3X-ray3.00B495-526[»]
5W3NNMR-A/B/C/D/E/F/G/H/I2-214[»]
5XRRX-ray1.50A54-59[»]
5XSGelectron microscopy0.73A37-42[»]
6BZPelectron microscopy1.10A/B77-82[»]
DisProtiDP01102
ProteinModelPortaliP35637
SMRiP35637
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini285 – 371RRMPROSITE-ProRule annotationAdd BLAST87

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 165Gln/Gly/Ser/Tyr-richAdd BLAST165
Compositional biasi166 – 267Gly-richAdd BLAST102
Compositional biasi371 – 526Arg/Gly-richAdd BLAST156

Sequence similaritiesi

Belongs to the RRM TET family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri422 – 453RanBP2-typePROSITE-ProRule annotationAdd BLAST32

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IP58 Eukaryota
ENOG4111GEG LUCA
GeneTreeiENSGT00530000063105
HOGENOMiHOG000038010
HOVERGENiHBG095056
InParanoidiP35637
KOiK13098
PhylomeDBiP35637
TreeFamiTF322599

Family and domain databases

Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR034459 FUS
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
IPR034870 TET_fam
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PANTHERiPTHR23238 PTHR23238, 1 hit
PTHR23238:SF5 PTHR23238:SF5, 1 hit
PfamiView protein in Pfam
PF00076 RRM_1, 1 hit
PF00641 zf-RanBP, 1 hit
SMARTiView protein in SMART
SM00360 RRM, 1 hit
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P35637-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YSQSTDTSGY
60 70 80 90 100
GQSSYSSYGQ SQNTGYGTQS TPQGYGSTGG YGSSQSSQSS YGQQSSYPGY
110 120 130 140 150
GQQPAPSSTS GSYGSSSQSS SYGQPQSGSY SQQPSYGGQQ QSYGQQQSYN
160 170 180 190 200
PPQGYGQQNQ YNSSSGGGGG GGGGGNYGQD QSSMSSGGGS GGGYGNQDQS
210 220 230 240 250
GGGGSGGYGQ QDRGGRGRGG SGGGGGGGGG GYNRSSGGYE PRGRGGGRGG
260 270 280 290 300
RGGMGGSDRG GFNKFGGPRD QGSRHDSEQD NSDNNTIFVQ GLGENVTIES
310 320 330 340 350
VADYFKQIGI IKTNKKTGQP MINLYTDRET GKLKGEATVS FDDPPSAKAA
360 370 380 390 400
IDWFDGKEFS GNPIKVSFAT RRADFNRGGG NGRGGRGRGG PMGRGGYGGG
410 420 430 440 450
GSGGGGRGGF PSGGGGGGGQ QRAGDWKCPN PTCENMNFSW RNECNQCKAP
460 470 480 490 500
KPDGPGGGPG GSHMGGNYGD DRRGGRGGYD RGGYRGRGGD RGGFRGGRGG
510 520
GDRGGFGPGK MDSRGEHRQD RRERPY
Length:526
Mass (Da):53,426
Last modified:June 1, 1994 - v1
Checksum:i88C8E263B7905549
GO
Isoform Short (identifier: P35637-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     64-65: TG → S

Show »
Length:525
Mass (Da):53,355
Checksum:i949558C718B4C19B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti338T → N AA sequence (PubMed:10567410).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068918191G → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs148758737Ensembl.1
Natural variantiVAR_068919216R → C in ALS6 and ETM4. 2 PublicationsCorresponds to variant dbSNP:rs267606832EnsemblClinVar.1
Natural variantiVAR_068920225G → V in ALS6. 1 Publication1
Natural variantiVAR_068921230G → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs748374535Ensembl.1
Natural variantiVAR_068922234R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs777819849Ensembl.1
Natural variantiVAR_054837244R → C in ALS6. 1 Publication1
Natural variantiVAR_065229254M → V Found in a patient with frontotemporal lobar degeneration. 1 PublicationCorresponds to variant dbSNP:rs752076094EnsemblClinVar.1
Natural variantiVAR_035481312K → Q in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_068923431P → L in ETM4. 1 PublicationCorresponds to variant dbSNP:rs186547381EnsemblClinVar.1
Natural variantiVAR_068924507G → D in ALS6. 1 PublicationCorresponds to variant dbSNP:rs267606831EnsemblClinVar.1
Natural variantiVAR_054838514R → G in ALS6. 1 Publication1
Natural variantiVAR_054839514R → S in ALS6. 1 Publication1
Natural variantiVAR_054840515G → C in ALS6. 1 Publication1
Natural variantiVAR_054841517H → Q Does not affect protein nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs121909667EnsemblClinVar.1
Natural variantiVAR_054842518R → K in ALS6. 1 PublicationCorresponds to variant dbSNP:rs121909669EnsemblClinVar.1
Natural variantiVAR_054843521R → C in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 3 PublicationsCorresponds to variant dbSNP:rs121909668EnsemblClinVar.1
Natural variantiVAR_054844521R → G in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 1 PublicationCorresponds to variant dbSNP:rs121909668EnsemblClinVar.1
Natural variantiVAR_054845521R → H in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 4 PublicationsCorresponds to variant dbSNP:rs121909671EnsemblClinVar.1
Natural variantiVAR_054846522R → G in ALS6. 1 Publication1
Natural variantiVAR_054847524R → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041389EnsemblClinVar.1
Natural variantiVAR_054848524R → T in ALS6. 1 Publication1
Natural variantiVAR_054849525P → L in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041390EnsemblClinVar.1
Natural variantiVAR_077328526Y → YY in ALS6; unknown pathological significance. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00579864 – 65TG → S in isoform Short. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S62140 mRNA Translation: AAB27102.1
S62138 mRNA Translation: AAB27103.1 Sequence problems.
X71427 mRNA Translation: CAA50558.1 Sequence problems.
X71428 mRNA Translation: CAA50559.1 Sequence problems.
AF071213 Genomic DNA Translation: AAC35285.1
AF071213 Genomic DNA Translation: AAC35284.1
AC009088 Genomic DNA No translation available.
BC000402 mRNA Translation: AAH00402.1
BC002459 mRNA Translation: AAH02459.1
AJ295163 mRNA Translation: CAC15058.1 Different termination.
CCDSiCCDS10707.1 [P35637-1]
CCDS58454.1 [P35637-2]
PIRiS33798
S33799
RefSeqiNP_001164105.1, NM_001170634.1 [P35637-2]
NP_004951.1, NM_004960.3 [P35637-1]
UniGeneiHs.46894

Genome annotation databases

EnsembliENST00000254108; ENSP00000254108; ENSG00000089280 [P35637-1]
ENST00000380244; ENSP00000369594; ENSG00000089280 [P35637-2]
GeneIDi2521
KEGGihsa:2521
UCSCiuc002ebh.4 human [P35637-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFUS_HUMAN
AccessioniPrimary (citable) accession number: P35637
Secondary accession number(s): Q9H4A8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 20, 2018
This is version 205 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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