Reviewed, UniProtKB/Swiss-Prot P35637 (FUS_HUMAN)

Names and origin

Protein names

Recommended name:
    RNA-binding protein FUS
Alternative name(s):
    Oncogene FUS
    Oncogene TLS
    Translocated in liposarcoma protein
    POMp75
    75 kDa DNA-pairing protein

Gene names

Name:	FUS
Synonyms:	TLS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	526 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1. Interacts through its C-terminus with FUSIP1. Ref.10 Ref.11 Ref.13
Subcellular location	Nucleus. Ref.16 Ref.17
Tissue specificity	Ubiquitous.
Post-translational modification	Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine. Ref.12
Involvement in disease	A chromosomal aberration involving FUS is a cause of a form of malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. A chromosomal aberration involving FUS is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. Defects in FUS are the cause of amyotrophic lateral sclerosis type 6 (ALS6) [MIM:608030]. ALS6 is a familial form of amyotrophic lateral sclerosis. ALS is a 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. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10%. Ref.16 Ref.17
Sequence similarities	Belongs to the RRM TET family. Contains 1 RanBP2-type zinc finger. Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Amyotrophic lateral sclerosis Disease mutation Neurodegeneration Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding RNA-binding Zinc
PTM	Methylation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW nuclear mRNA splicing, via spliceosome Inferred from Experiment. Source: Reactome
Cellular component	nucleus Ref.1 Inferred from direct assay. Source: HPA
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Ref.1 Traceable author statement. Source: ProtInc protein binding Ref.11 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF6	P56537	1	EBI-400434,EBI-372243
USF2	Q15853	1	EBI-400434,EBI-1055994

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P35637-1)

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.

Isoform Short (identifier: P35637-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 526	526	RNA-binding protein FUS		PRO_0000081591
Regions
	Domain	285 – 371	87	RRM
	Zinc finger	422 – 453	32	RanBP2-type
	Compositional bias	1 – 165	165	Gln/Gly/Ser/Tyr-rich
	Compositional bias	166 – 267	102	Gly-rich
	Compositional bias	371 – 526	156	Arg/Gly-rich
Sites
	Site	175	1	Breakpoint for translocation to form chimeric FUS/ATF1 protein
	Site	266 – 267	2	Breakpoint for translocation to form FUS/TLS-CHOP oncogene
Amino acid modifications
	Modified residue	216	1	Omega-N-methylated arginine Ref.12
	Modified residue	218	1	Omega-N-methylated arginine Ref.12
Natural variations
	Alternative sequence	64 – 65	2	TG → S in isoform Short.		VSP_005798
	Natural variant	244	1	R → C in ALS6. Ref.16		VAR_054837
	Natural variant	312	1	K → Q in a breast cancer sample; somatic mutation. Ref.15		VAR_035481
	Natural variant	514	1	R → G in ALS6. Ref.16 Ref.17		VAR_054838
	Natural variant	514	1	R → S in ALS6. Ref.16 Ref.17		VAR_054839
	Natural variant	515	1	G → C in ALS6. Ref.16		VAR_054840
	Natural variant	517	1	H → Q Does not affect protein nuclear localization. Ref.16		VAR_054841
	Natural variant	518	1	R → K in ALS6. Ref.16		VAR_054842
	Natural variant	521	1	R → C in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. Ref.16 Ref.17		VAR_054843
	Natural variant	521	1	R → G in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. Ref.16 Ref.17		VAR_054844
	Natural variant	521	1	R → H in ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. Ref.16 Ref.17		VAR_054845
	Natural variant	522	1	R → G in ALS6. Ref.16		VAR_054846
	Natural variant	524	1	R → S in ALS6. Ref.16		VAR_054847
	Natural variant	524	1	R → T in ALS6. Ref.16		VAR_054848
	Natural variant	525	1	P → L in ALS6. Ref.16		VAR_054849
Experimental info
	Sequence conflict	338	1	T → N AA sequence Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 88C8E263B7905549	FASTA	526	53,426
	10 20 30 40 50 60 MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YSQSTDTSGY GQSSYSSYGQ 70 80 90 100 110 120 SQNTGYGTQS TPQGYGSTGG YGSSQSSQSS YGQQSSYPGY GQQPAPSSTS GSYGSSSQSS 130 140 150 160 170 180 SYGQPQSGSY SQQPSYGGQQ QSYGQQQSYN PPQGYGQQNQ YNSSSGGGGG GGGGGNYGQD 190 200 210 220 230 240 QSSMSSGGGS GGGYGNQDQS GGGGSGGYGQ QDRGGRGRGG SGGGGGGGGG GYNRSSGGYE 250 260 270 280 290 300 PRGRGGGRGG RGGMGGSDRG GFNKFGGPRD QGSRHDSEQD NSDNNTIFVQ GLGENVTIES 310 320 330 340 350 360 VADYFKQIGI IKTNKKTGQP MINLYTDRET GKLKGEATVS FDDPPSAKAA IDWFDGKEFS 370 380 390 400 410 420 GNPIKVSFAT RRADFNRGGG NGRGGRGRGG PMGRGGYGGG GSGGGGRGGF PSGGGGGGGQ 430 440 450 460 470 480 QRAGDWKCPN PTCENMNFSW RNECNQCKAP KPDGPGGGPG GSHMGGNYGD DRRGGRGGYD 490 500 510 520 RGGYRGRGGD RGGFRGGRGG GDRGGFGPGK MDSRGEHRQD RRERPY
	Isoform Short. Checksum: 949558C718B4C19B	FASTA	525	53,355
	10 20 30 40 50 60 MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YSQSTDTSGY GQSSYSSYGQ 70 80 90 100 110 120 SQNSYGTQST PQGYGSTGGY GSSQSSQSSY GQQSSYPGYG QQPAPSSTSG SYGSSSQSSS 130 140 150 160 170 180 YGQPQSGSYS QQPSYGGQQQ SYGQQQSYNP PQGYGQQNQY NSSSGGGGGG GGGGNYGQDQ 190 200 210 220 230 240 SSMSSGGGSG GGYGNQDQSG GGGSGGYGQQ DRGGRGRGGS GGGGGGGGGG YNRSSGGYEP 250 260 270 280 290 300 RGRGGGRGGR GGMGGSDRGG FNKFGGPRDQ GSRHDSEQDN SDNNTIFVQG LGENVTIESV 310 320 330 340 350 360 ADYFKQIGII KTNKKTGQPM INLYTDRETG KLKGEATVSF DDPPSAKAAI DWFDGKEFSG 370 380 390 400 410 420 NPIKVSFATR RADFNRGGGN GRGGRGRGGP MGRGGYGGGG SGGGGRGGFP SGGGGGGGQQ 430 440 450 460 470 480 RAGDWKCPNP TCENMNFSWR NECNQCKAPK PDGPGGGPGG SHMGGNYGDD RRGGRGGYDR 490 500 510 520 GGYRGRGGDR GGFRGGRGGG DRGGFGPGKM DSRGEHRQDR RERPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma." Crozat A., Aman P., Mandahl N., Ron D. Nature 363:640-644(1993) [PubMed: 8510758] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]	"Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma." Rabbitts T.H., Forster A., Larson R., Nathan P. Nat. Genet. 4:175-180(1993) [PubMed: 7503811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[3]	"Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes." Morohoshi F., Ootsuka Y., Arai K., Ichikawa H., Mitani S., Munakata N., Ohki M. Gene 221:191-198(1998) [PubMed: 9795213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS LONG AND SHORT).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Lung and Lymph.
[5]	"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 B.L., Panagopoulos I., Allen E.F. Cancer Genet. Cytogenet. 121:109-116(2000) [PubMed: 11063792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-310, CHROMOSOMAL TRANSLOCATION WITH ATF1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
[6]	"Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation." Baechtold H., Kuroda M., Sok J., Ron D., Lopez B.S., Akhmedov A.T. J. Biol. Chem. 274:34337-34342(1999) [PubMed: 10567410] [Abstract] Cited for: PROTEIN SEQUENCE OF 235-244; 307-312; 335-345 AND 349-357, CHARACTERIZATION.
[7]	"Human POMp75 is identified as the pro-oncoprotein TLF/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell prolifieration." Bertrand P., Akhmedov A.T., Delacote F., Durrbach A., Lopez B.S. Oncogene 18:4515-4521(1999) [PubMed: 10442642] [Abstract] Cited for: PROTEIN SEQUENCE OF 265-276; 317-331 AND 335-357, IDENTIFICATION.
[8]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 349-357, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[9]	"An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation." Ichikawa H., Shimizu K., Hayashi Y., Ohki M. Cancer Res. 54:2865-2868(1994) [PubMed: 8187069] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION.
[10]	"The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription." Zhang D., Paley A.J., Childs G. J. Biol. Chem. 273:18086-18091(1998) [PubMed: 9660765] [Abstract] Cited for: INTERACTION WITH SF1.
[11]	"Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing." Yang L., Embree L.J., Tsai S., Hickstein D.D. J. Biol. Chem. 273:27761-27764(1998) [PubMed: 9774382] [Abstract] Cited for: INTERACTION WITH FUSIP1.
[12]	"Identifying and quantifying in vivo methylation sites by heavy methyl SILAC." Ong S.E., Mittler G., Mann M. Nat. Methods 1:119-126(2004) [PubMed: 15782174] [Abstract] Cited for: METHYLATION [LARGE SCALE ANALYSIS] AT ARG-216 AND ARG-218, MASS SPECTROMETRY.
[13]	"TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules." Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J. Hum. Mol. Genet. 17:3055-3074(2008) [PubMed: 18632687] [Abstract] Cited for: INTERACTION WITH TDRD3.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-312.
[16]	"Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis." Kwiatkowski T.J. Jr., Bosco D.A., Leclerc A.L., Tamrazian E., Vanderburg C.R., Russ C., Davis A., Gilchrist J., Kasarskis E.J., Munsat T., Valdmanis P., Rouleau G.A., Hosler B.A., Cortelli P., de Jong P.J., Yoshinaga Y., Haines J.L., Pericak-Vance M.A. , Yan J., Ticozzi N., Siddique T., McKenna-Yasek D., Sapp P.C., Horvitz H.R., Landers J.E., Brown R.H. Jr. Science 323:1205-1208(2009) [PubMed: 19251627] [Abstract] Cited for: VARIANTS ALS6 CYS-244; SER-514; CYS-515; LYS-518; CYS-521; GLY-521; HIS-521; GLY-522; SER-524; THR-524 AND LEU-525, VARIANT GLN-517, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT ALS6 GLY-521, CHARACTERIZATION OF VARIANT GLN-517.
[17]	"Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6." Vance C., Rogelj B., Hortobagyi T., De Vos K.J., Nishimura A.L., Sreedharan J., Hu X., Smith B., Ruddy D., Wright P., Ganesalingam J., Williams K.L., Tripathi V., Al-Saraj S., Al-Chalabi A., Leigh P.N., Blair I.P., Nicholson G. , de Belleroche J., Gallo J.M., Miller C.C., Shaw C.E. Science 323:1208-1211(2009) [PubMed: 19251628] [Abstract] Cited for: VARIANTS ALS6 GLY-514; CYS-521 AND HIS-521, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS ALS6 CYS-521 AND HIS-521.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. BC000402 mRNA. Translation: AAH00402.1. BC002459 mRNA. Translation: AAH02459.1. AJ295163 mRNA. Translation: CAC15058.1. Different termination.
IPI	IPI00221354. IPI00260715.
PIR	S33798. S33799.
RefSeq	NP_004951.1.
UniGene	Hs.513522
3D structure databases
HSSP	HSSP built from PDB template 1L3K based on UniProtKB P09651.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35637. 12 interactions.
PTM databases
PhosphoSite	P35637.
Proteomic databases
PRIDE	P35637.
Genome annotation databases
Ensembl	ENSG00000089280. Homo sapiens. [Contig view]
GeneID	2521.
KEGG	hsa:2521.
Organism-specific databases
GeneCards	GC16P031098.
H-InvDB	HIX0012983.
HGNC	HGNC:4010. FUS.
HPA	HPA008784.
MIM	137070. gene. 608030. phenotype. 612160. phenotype.
Orphanet	519. Leukemia, myeloid, acute. 99967. Myxoid liposarcoma.
PharmGKB	PA28425.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P35637.
OMA	P35637. QSYSGYS.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_6167. Influenza Infection. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P35637.
Bgee	P35637.
CleanEx	HS_FUS.
GermOnline	ENSG00000089280. Homo sapiens.
Family and domain databases
InterPro	IPR000504. RRM_RNP1. IPR001876. Znf_RanBP2. [Graphical view]
Pfam	PF00076. RRM_1. 1 hit. PF00641. zf-RanBP. 1 hit. [Graphical view]
SMART	SM00360. RRM. 1 hit. SM00547. ZnF_RBZ. 1 hit. [Graphical view]
PROSITE	PS50102. RRM. 1 hit. PS01358. ZF_RANBP2_1. 1 hit. PS50199. ZF_RANBP2_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	9927.
SOURCE	Search...

Entry information

Entry name

FUS_HUMAN

Accession

Primary (citable) accession number: P35637
Secondary accession number(s): Q9H4A8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)