FUS

Functionⁱ

DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Binds also its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity).By similarity4 Publications

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	422 – 453	RanBP2-typePROSITE-ProRule annotationAdd BLAST		32

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	DNA-binding, RNA-binding
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-HSA-72163 mRNA Splicing - Major Pathway
SIGNORⁱ	P35637

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 16

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000089280.18
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:4010 FUS
MIMⁱ	137070 gene
neXtProtⁱ	NX_P35637

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.

Related information in OMIM

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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_068918	191	G → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs148758737Ensembl.	1
Natural variantⁱVAR_068919	216	R → C in ALS6 and ETM4. 2 PublicationsCorresponds to variant dbSNP:rs267606832EnsemblClinVar.	1
Natural variantⁱVAR_068920	225	G → V in ALS6. 1 Publication	1
Natural variantⁱVAR_068921	230	G → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs748374535Ensembl.	1
Natural variantⁱVAR_068922	234	R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs777819849Ensembl.	1
Natural variantⁱVAR_054837	244	R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs1165095258Ensembl.	1
Natural variantⁱVAR_068924	507	G → D in ALS6. 1 PublicationCorresponds to variant dbSNP:rs267606831EnsemblClinVar.	1
Natural variantⁱVAR_054838	514	R → G in ALS6. 1 Publication	1
Natural variantⁱVAR_054839	514	R → S in ALS6. 1 Publication	1
Natural variantⁱVAR_054840	515	G → C in ALS6. 1 Publication	1
Natural variantⁱVAR_054842	518	R → K in ALS6. 1 PublicationCorresponds to variant dbSNP:rs121909669EnsemblClinVar.	1
Natural variantⁱVAR_054843	521	R → C in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 3 PublicationsCorresponds to variant dbSNP:rs121909668EnsemblClinVar.	1
Natural variantⁱVAR_054844	521	R → G in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 1 PublicationCorresponds to variant dbSNP:rs121909668EnsemblClinVar.	1
Natural variantⁱVAR_054845	521	R → H in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 4 PublicationsCorresponds to variant dbSNP:rs121909671EnsemblClinVar.	1
Natural variantⁱVAR_054846	522	R → G in ALS6. 1 PublicationCorresponds to variant dbSNP:rs1555509693EnsemblClinVar.	1
Natural variantⁱVAR_054847	524	R → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041389EnsemblClinVar.	1
Natural variantⁱVAR_054848	524	R → T in ALS6. 1 Publication	1
Natural variantⁱVAR_054849	525	P → L in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041390EnsemblClinVar.	1
Natural variantⁱVAR_077328	526	Y → YY in ALS6; unknown pathological significance. 1 Publication	1

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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_068919	216	R → C in ALS6 and ETM4. 2 PublicationsCorresponds to variant dbSNP:rs267606832EnsemblClinVar.		1
Natural variantⁱVAR_068923	431	P → L in ETM4. 1 PublicationCorresponds to variant dbSNP:rs186547381EnsemblClinVar.		1

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	175	Breakpoint for translocation to form chimeric FUS/ATF1 protein		1
Siteⁱ	266 – 267	Breakpoint for translocation to form FUS/TLS-CHOP oncogene		2

Keywords - Diseaseⁱ

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

Organism-specific databases

DisGeNET More...DisGeNETⁱ	2521
GeneReviewsⁱ	FUS
MalaCards human disease database More...MalaCardsⁱ	FUS
MIMⁱ	608030 phenotype 612160 phenotype 614782 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000089280
Orphanetⁱ	803 Amyotrophic lateral sclerosis 275872 Frontotemporal dementia with motor neuron disease 300605 Juvenile amyotrophic lateral sclerosis 79105 Myxofibrosarcoma 99967 Myxoid/round cell liposarcoma 862 NON RARE IN EUROPE: Hereditary essential tremor
PharmGKBⁱ	PA28425

Miscellaneous databases

Pharosⁱ	P35637 Tbio

Pharosⁱ

P35637 Tbio

Polymorphism and mutation databases

BioMutaⁱ	FUS
DMDMⁱ	544357

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000081591	1 – 526	RNA-binding protein FUSAdd BLAST		526

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	26	Phosphoserine1 Publication	1
Modified residueⁱ	30	Phosphoserine1 Publication	1
Modified residueⁱ	42	Phosphoserine; by ATM1 Publication	1
Modified residueⁱ	216	Asymmetric dimethylarginine; alternateCombined sources	1
Modified residueⁱ	216	Omega-N-methylarginine; alternateCombined sources	1
Modified residueⁱ	218	Asymmetric dimethylarginine; alternateCombined sources	1
Modified residueⁱ	218	Omega-N-methylarginine; alternateCombined sources	1
Modified residueⁱ	221	PhosphoserineCombined sources	1
Modified residueⁱ	242	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	244	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	248	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	251	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	259	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	277	PhosphoserineCombined sources	1
Modified residueⁱ	286	PhosphothreonineCombined sources	1
Cross-linkⁱ	334	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	340	PhosphoserineCombined sources	1
Modified residueⁱ	377	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	383	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	386	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	388	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	394	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	407	Asymmetric dimethylarginine; alternate1 Publication	1
Modified residueⁱ	407	Omega-N-methylarginine; alternateBy similarity	1
Modified residueⁱ	473	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	476	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	481	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	485	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	487	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	491	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	495	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	498	Asymmetric dimethylarginine1 Publication	1
Modified residueⁱ	503	Asymmetric dimethylarginine; alternate1 Publication	1
Modified residueⁱ	503	Omega-N-methylarginine; alternateCombined sources	1

Post-translational modificationⁱ

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

Keywords - PTMⁱ

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	P35637
jPOSTⁱ	P35637
MassIVEⁱ	P35637
PaxDbⁱ	P35637
PeptideAtlas More...PeptideAtlasⁱ	P35637
PRIDEⁱ	P35637
ProteomicsDBⁱ	55119 [P35637-1] 55120 [P35637-2]
TopDownProteomicsⁱ	P35637-1 [P35637-1] P35637-2 [P35637-2]

PTM databases

iPTMnetⁱ	P35637
PhosphoSitePlusⁱ	P35637
SwissPalmⁱ	P35637

Expressionⁱ

Tissue specificityⁱ

Ubiquitous.

Gene expression databases

Bgeeⁱ	ENSG00000089280 Expressed in 238 organ(s), highest expression level in right testis
ExpressionAtlasⁱ	P35637 baseline and differential
Genevisibleⁱ	P35637 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB033036 CAB058691 HPA008784

HPAⁱ

CAB033036
CAB058691
HPA008784

Interactionⁱ

Subunit structureⁱ

Self-oligomerizes (via N-terminal region) (PubMed:25453086). Oligomerization is essential for chromatin binding (PubMed:25453086).

Component of nuclear riboprotein complexes.

Interacts with ILF3, TDRD3 and SF1 (PubMed:9660765).

Interacts through its C-terminus with SFRS13A (PubMed:9774382).

Interacts with OTUB1 and SARNP.

Interacts with LRSAM1 (PubMed:27615052).

Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin (PubMed:27731383).

Interacts with MATR3 (PubMed:27731383).

Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing (PubMed:26124092).

Interacts (through its RNA-binding domain) with RALY (through its RNA-binding domain); both are components of the same RNPs (PubMed:30354839).

9 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-400434,EBI-400434
	P45481	4	EBI-400434,EBI-296306	From Mus musculus.
	Q9NRR4	2	EBI-400434,EBI-528367
	Q09472	4	EBI-400434,EBI-447295
	Q01844	5	EBI-400434,EBI-739737
	Q92993	2	EBI-400434,EBI-399080
	Q15149	4	EBI-400434,EBI-297903
	Q99873	5	EBI-400434,EBI-78738
	Q99873-3	3	EBI-400434,EBI-17165527
	P38159	5	EBI-400434,EBI-743526
	Q15424	7	EBI-400434,EBI-348298
	Q92804	7	EBI-400434,EBI-2255091
	Q92973-2	2	EBI-400434,EBI-11022821
	Q9H3D4	2	EBI-400434,EBI-2337775

Show more details

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	108797, 458 interactors
CORUMⁱ	P35637
Database of interacting proteins More...DIPⁱ	DIP-29857N
IntActⁱ	P35637, 193 interactors
Molecular INTeraction database More...MINTⁱ	P35637
STRINGⁱ	9606.ENSP00000254108

Miscellaneous databases

RNActⁱ	P35637 protein

RNActⁱ

P35637 protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	38 – 40	Combined sources	3
Beta strandⁱ	47 – 49	Combined sources	3
Beta strandⁱ	59 – 64	Combined sources	6
Beta strandⁱ	67 – 70	Combined sources	4
Beta strandⁱ	73 – 75	Combined sources	3
Beta strandⁱ	93 – 95	Combined sources	3
Beta strandⁱ	285 – 290	Combined sources	6
Helixⁱ	298 – 305	Combined sources	8
Turnⁱ	306 – 308	Combined sources	3
Turnⁱ	315 – 318	Combined sources	4
Beta strandⁱ	319 – 326	Combined sources	8
Turnⁱ	328 – 330	Combined sources	3
Beta strandⁱ	332 – 343	Combined sources	12
Helixⁱ	344 – 354	Combined sources	11
Beta strandⁱ	358 – 363	Combined sources	6
Beta strandⁱ	365 – 368	Combined sources	4
Helixⁱ	372 – 375	Combined sources	4
Beta strandⁱ	379 – 381	Combined sources	3
Turnⁱ	431 – 433	Combined sources	3
Turnⁱ	445 – 447	Combined sources	3
Beta strandⁱ	450 – 452	Combined sources	3
Helixⁱ	514 – 521	Combined sources	8

Show more details

3D structure databases

SMRⁱ	P35637
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	285 – 371	RRMPROSITE-ProRule annotationAdd BLAST		87

Compositional bias

Feature key	Position(s)	DescriptionActions	Length
Compositional biasⁱ	1 – 165	Gln/Gly/Ser/Tyr-richAdd BLAST	165
Compositional biasⁱ	166 – 267	Gly-richAdd BLAST	102
Compositional biasⁱ	371 – 526	Arg/Gly-richAdd BLAST	156

Sequence similaritiesⁱ

Belongs to the RRM TET family.Curated

Zinc finger

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	422 – 453	RanBP2-typePROSITE-ProRule annotationAdd BLAST		32

Keywords - Domainⁱ

Repeat, Zinc-finger

Phylogenomic databases

eggNOGⁱ	ENOG410IP58 Eukaryota ENOG4111GEG LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000157290
HOGENOMⁱ	HOG000038010
InParanoidⁱ	P35637
KEGG Orthology (KO) More...KOⁱ	K13098
Database of Orthologous Groups More...OrthoDBⁱ	334242at2759
PhylomeDBⁱ	P35637
TreeFamⁱ	TF322599

Family and domain databases

Database of protein disorder More...DisProtⁱ	DP01102
Gene3Dⁱ	3.30.70.330, 1 hit
InterProⁱ	View 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
PANTHERⁱ	PTHR23238 PTHR23238, 1 hit PTHR23238:SF5 PTHR23238:SF5, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00076 RRM_1, 1 hit PF00641 zf-RanBP, 1 hit
SMARTⁱ	View protein in SMART SM00360 RRM, 1 hit SM00547 ZnF_RBZ, 1 hit
SUPFAMⁱ	SSF54928 SSF54928, 1 hit SSF90209 SSF90209, 1 hit
PROSITEⁱ	View 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. Align Add to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show all Align All

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

This isoform has been chosen as the canonicalⁱ 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]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YSQSTDTSGY 
        60         70         80         90        100
GQSSYSSYGQ SQNSYGTQST PQGYGSTGGY GSSQSSQSSY GQQSSYPGYG 
       110        120        130        140        150
QQPAPSSTSG SYGSSSQSSS YGQPQSGSYS QQPSYGGQQQ SYGQQQSYNP 
       160        170        180        190        200
PQGYGQQNQY NSSSGGGGGG GGGGNYGQDQ SSMSSGGGSG GGYGNQDQSG 
       210        220        230        240        250
GGGSGGYGQQ DRGGRGRGGS GGGGGGGGGG YNRSSGGYEP RGRGGGRGGR 
       260        270        280        290        300
GGMGGSDRGG FNKFGGPRDQ GSRHDSEQDN SDNNTIFVQG LGENVTIESV 
       310        320        330        340        350
ADYFKQIGII KTNKKTGQPM INLYTDRETG KLKGEATVSF DDPPSAKAAI 
       360        370        380        390        400
DWFDGKEFSG NPIKVSFATR RADFNRGGGN GRGGRGRGGP MGRGGYGGGG 
       410        420        430        440        450
SGGGGRGGFP SGGGGGGGQQ RAGDWKCPNP TCENMNFSWR NECNQCKAPK 
       460        470        480        490        500
PDGPGGGPGG SHMGGNYGDD RRGGRGGYDR GGYRGRGGDR GGFRGGRGGG 
       510        520 
DRGGFGPGKM DSRGEHRQDR RERPY

Show »

Length:525

Mass (Da):53,355

Checksum:ⁱ949558C718B4C19B

GO

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

H3BPE7	H3BPE7_HUMAN	RNA-binding protein FUS RNA-binding protein FUS	FUS	527	Annotation score:
H3BNZ4	H3BNZ4_HUMAN	RNA-binding protein FUS RNA-binding protein FUS	FUS	263	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	338	T → N AA sequence (PubMed:10567410).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_068918	191	G → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs148758737Ensembl.	1
Natural variantⁱVAR_068919	216	R → C in ALS6 and ETM4. 2 PublicationsCorresponds to variant dbSNP:rs267606832EnsemblClinVar.	1
Natural variantⁱVAR_068920	225	G → V in ALS6. 1 Publication	1
Natural variantⁱVAR_068921	230	G → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs748374535Ensembl.	1
Natural variantⁱVAR_068922	234	R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs777819849Ensembl.	1
Natural variantⁱVAR_054837	244	R → C in ALS6. 1 PublicationCorresponds to variant dbSNP:rs1165095258Ensembl.	1
Natural variantⁱVAR_065229	254	M → V Found in a patient with frontotemporal lobar degeneration. 1 PublicationCorresponds to variant dbSNP:rs752076094EnsemblClinVar.	1
Natural variantⁱVAR_035481	312	K → Q in a breast cancer sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_068923	431	P → L in ETM4. 1 PublicationCorresponds to variant dbSNP:rs186547381EnsemblClinVar.	1
Natural variantⁱVAR_068924	507	G → D in ALS6. 1 PublicationCorresponds to variant dbSNP:rs267606831EnsemblClinVar.	1
Natural variantⁱVAR_054838	514	R → G in ALS6. 1 Publication	1
Natural variantⁱVAR_054839	514	R → S in ALS6. 1 Publication	1
Natural variantⁱVAR_054840	515	G → C in ALS6. 1 Publication	1
Natural variantⁱVAR_054841	517	H → Q Does not affect protein nuclear localization. 1 PublicationCorresponds to variant dbSNP:rs121909667EnsemblClinVar.	1
Natural variantⁱVAR_054842	518	R → K in ALS6. 1 PublicationCorresponds to variant dbSNP:rs121909669EnsemblClinVar.	1
Natural variantⁱVAR_054843	521	R → C in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 3 PublicationsCorresponds to variant dbSNP:rs121909668EnsemblClinVar.	1
Natural variantⁱVAR_054844	521	R → G in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 1 PublicationCorresponds to variant dbSNP:rs121909668EnsemblClinVar.	1
Natural variantⁱVAR_054845	521	R → H in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. 4 PublicationsCorresponds to variant dbSNP:rs121909671EnsemblClinVar.	1
Natural variantⁱVAR_054846	522	R → G in ALS6. 1 PublicationCorresponds to variant dbSNP:rs1555509693EnsemblClinVar.	1
Natural variantⁱVAR_054847	524	R → S in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041389EnsemblClinVar.	1
Natural variantⁱVAR_054848	524	R → T in ALS6. 1 Publication	1
Natural variantⁱVAR_054849	525	P → L in ALS6. 1 PublicationCorresponds to variant dbSNP:rs886041390EnsemblClinVar.	1
Natural variantⁱVAR_077328	526	Y → YY in ALS6; unknown pathological significance. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_005798	64 – 65	TG → S in isoform Short. 1 Publication		2

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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS10707.1 [P35637-1] CCDS58454.1 [P35637-2]
PIRⁱ	S33798 S33799
NCBI Reference Sequences More...RefSeqⁱ	NP_001164105.1, NM_001170634.1 [P35637-2] NP_004951.1, NM_004960.3 [P35637-1]

Genome annotation databases

Ensemblⁱ	ENST00000254108; ENSP00000254108; ENSG00000089280 [P35637-1] ENST00000380244; ENSP00000369594; ENSG00000089280 [P35637-2]
GeneIDⁱ	2521
KEGGⁱ	hsa:2521
UCSC genome browser More...UCSCⁱ	uc002ebh.4 human [P35637-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P35637	FUS protein		HUMAN		526	UniRef100_P35637
UPI000D5FE126		HUMAN		528

Protein	Similar proteins		Species	Score	Length	Source
P35637	RNA-binding protein FUS		MOUSE		518	UniRef90_P35637
RNA-binding protein FUS		BOVIN		513
FUS protein		HUMAN		526
FUS RNA binding protein		CALJA		607
RRM domain-containing protein (Fragment)		NEOVI		91
+243

Protein	Similar proteins		Species	Score	Length	Source
P35637	RNA-binding protein FUS		MOUSE		518	UniRef50_P35637
RNA-binding protein FUS		BOVIN		513
FUS protein		HUMAN		526
FUS RNA binding protein		CALJA		607
RRM domain-containing protein (Fragment)		NEOVI		91
+262

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
CCDSⁱ	CCDS10707.1 [P35637-1] CCDS58454.1 [P35637-2]
PIRⁱ	S33798 S33799
RefSeqⁱ	NP_001164105.1, NM_001170634.1 [P35637-2] NP_004951.1, NM_004960.3 [P35637-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2LA6	NMR	-	A	282-370	[»]
	2LCW	NMR	-	A	278-385	[»]
	4FDD	X-ray	2.30	B	498-526	[»]
	4FQ3	X-ray	3.00	B	495-526	[»]
	5W3N	NMR	-	A/B/C/D/E/F/G/H/I	2-214	[»]
	5XRR	X-ray	1.50	A	54-59	[»]
	5XSG	electron microscopy	0.73	A	37-42	[»]
	5YVG	X-ray	4.05	X/Y	1-526	[»]
	5YVH	X-ray	3.15	B	371-526	[»]
	5YVI	X-ray	2.90	B	456-526	[»]
	6BWZ	X-ray	1.10	A	37-42	[»]
	6BXV	X-ray	1.10	A	54-61	[»]
	6BZP	electron microscopy	1.10	A/B	77-82	[»]
	6G99	NMR	-	B	419-454	[»]
	6GBM	NMR	-	B	280-377	[»]
	6KJ1	electron microscopy	0.65	A	37-42	[»]
	6KJ2	electron microscopy	0.67	A	37-42	[»]
	6KJ3	electron microscopy	0.60	A	37-42	[»]
	6KJ4	electron microscopy	0.65	A	37-42	[»]
SMRⁱ	P35637
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	108797, 458 interactors
CORUMⁱ	P35637
DIPⁱ	DIP-29857N
IntActⁱ	P35637, 193 interactors
MINTⁱ	P35637
STRINGⁱ	9606.ENSP00000254108

PTM databases

iPTMnetⁱ	P35637
PhosphoSitePlusⁱ	P35637
SwissPalmⁱ	P35637

Polymorphism and mutation databases

BioMutaⁱ	FUS
DMDMⁱ	544357

Proteomic databases

EPDⁱ	P35637
jPOSTⁱ	P35637
MassIVEⁱ	P35637
PaxDbⁱ	P35637
PeptideAtlasⁱ	P35637
PRIDEⁱ	P35637
ProteomicsDBⁱ	55119 [P35637-1] 55120 [P35637-2]
TopDownProteomicsⁱ	P35637-1 [P35637-1] P35637-2 [P35637-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	2521

DNASUⁱ

2521

Genome annotation databases

Ensemblⁱ	ENST00000254108; ENSP00000254108; ENSG00000089280 [P35637-1] ENST00000380244; ENSP00000369594; ENSG00000089280 [P35637-2]
GeneIDⁱ	2521
KEGGⁱ	hsa:2521
UCSCⁱ	uc002ebh.4 human [P35637-1]

Organism-specific databases

CTDⁱ	2521
DisGeNETⁱ	2521
EuPathDBⁱ	HostDB:ENSG00000089280.18
GeneCardsⁱ	FUS
GeneReviewsⁱ	FUS
HGNCⁱ	HGNC:4010 FUS
HPAⁱ	CAB033036 CAB058691 HPA008784
MalaCardsⁱ	FUS
MIMⁱ	137070 gene 608030 phenotype 612160 phenotype 614782 phenotype
neXtProtⁱ	NX_P35637
OpenTargetsⁱ	ENSG00000089280
Orphanetⁱ	803 Amyotrophic lateral sclerosis 275872 Frontotemporal dementia with motor neuron disease 300605 Juvenile amyotrophic lateral sclerosis 79105 Myxofibrosarcoma 99967 Myxoid/round cell liposarcoma 862 NON RARE IN EUROPE: Hereditary essential tremor
PharmGKBⁱ	PA28425
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IP58 Eukaryota ENOG4111GEG LUCA
GeneTreeⁱ	ENSGT00940000157290
HOGENOMⁱ	HOG000038010
InParanoidⁱ	P35637
KOⁱ	K13098
OrthoDBⁱ	334242at2759
PhylomeDBⁱ	P35637
TreeFamⁱ	TF322599

Enzyme and pathway databases

Reactomeⁱ	R-HSA-72163 mRNA Splicing - Major Pathway
SIGNORⁱ	P35637

Miscellaneous databases

ChiTaRSⁱ	FUS human
GeneWikiⁱ	FUS
GenomeRNAiⁱ	2521
Pharosⁱ	P35637 Tbio
Protein Ontology More...PROⁱ	PR:P35637
RNActⁱ	P35637 protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000089280 Expressed in 238 organ(s), highest expression level in right testis
ExpressionAtlasⁱ	P35637 baseline and differential
Genevisibleⁱ	P35637 HS

Family and domain databases

DisProtⁱ	DP01102
Gene3Dⁱ	3.30.70.330, 1 hit
InterProⁱ	View 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
PANTHERⁱ	PTHR23238 PTHR23238, 1 hit PTHR23238:SF5 PTHR23238:SF5, 1 hit
Pfamⁱ	View protein in Pfam PF00076 RRM_1, 1 hit PF00641 zf-RanBP, 1 hit
SMARTⁱ	View protein in SMART SM00360 RRM, 1 hit SM00547 ZnF_RBZ, 1 hit
SUPFAMⁱ	SSF54928 SSF54928, 1 hit SSF90209 SSF90209, 1 hit
PROSITEⁱ	View protein in PROSITE PS50102 RRM, 1 hit PS01358 ZF_RANBP2_1, 1 hit PS50199 ZF_RANBP2_2, 1 hit
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	FUS_HUMAN
Accessionⁱ	P35637Primary (citable) accession number: P35637 Secondary accession number(s): Q9H4A8
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
	Last sequence update:	June 1, 1994
	Last modified:	December 11, 2019
	This is version 220 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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, Direct protein sequencing, Reference proteome

Documents

PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM

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UniProtKB - P35637 (FUS_HUMAN)

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RNA-binding protein FUS

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

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Keywords - Diseasei

Organism-specific databases

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Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

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Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Keywords - Domaini

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Experimental Info

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Alternative sequence

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Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

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Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

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Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ