Reviewed, UniProtKB/Swiss-Prot O75494 (FUSIP_HUMAN)

Names and origin

Protein names

Recommended name:
    FUS-interacting serine-arginine-rich protein 1
Alternative name(s):
    TLS-associated protein with Ser-Arg repeats
      Short name=TLS-associated protein with SR repeats
      Short name=TASR
    TLS-associated serine-arginine protein
      Short name=TLS-associated SR protein
    40 kDa SR-repressor protein
      Short name=SRrp40
    Splicing factor SRp38

Gene names

Name:	FUSIP1
Synonyms:	FUSIP2, TASR

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	262 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Splicing factor that in its dephosphorylated form acts as a general repressor of pre-mRNA splicing. Seems to interfere with the U1 snRNP 5'-splice recognition of SNRNP70. Required for splicing repression in M-phase cells and after heat shock. May be involved in regulation of alternative splicing in neurons, with isoform 1 acting as a positive and isoform 3 as a negative regulator. Ref.3 Ref.4 Ref.9
Subunit structure	The phosphorylated but not the dephosphorylated form interacts with TRA2B/SFRS10. The dephosphorylated form interacts with SNRNP70. Isoform 1 and isoform 3 interact with FUS C-terminus. Ref.9 Ref.1
Subcellular location	Nucleus speckle. Cytoplasm. Ref.3
Tissue specificity	Widely expressed. Ref.3 Ref.5
Post-translational modification	Phosphorylated. Fully dephosphorylated in mitosis and partially dephosphorylated on heat shock. Isoform 3 is phosphorylated on Ser-168 By similarity.
Sequence similarities	Belongs to the splicing factor SR family. Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	assembly of spliceosomal tri-snRNP Ref.3 Non-traceable author statement. Source: UniProtKB cytoplasmic transport Ref.3 Inferred from direct assay. Source: UniProtKB mRNA export from nucleus Ref.3 Non-traceable author statement. Source: UniProtKB mRNA splice site selection Ref.1 Inferred from direct assay. Source: UniProtKB negative regulation of nuclear mRNA splicing, via spliceosome Ref.3 Inferred from direct assay. Source: UniProtKB regulation of transcription Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Ref.3 Non-traceable author statement. Source: UniProtKB nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	RNA binding Ref.1 Non-traceable author statement. Source: UniProtKB RNA splicing factor activity, transesterification mechanism Ref.1 Inferred from direct assay. Source: UniProtKB RS domain binding Ref.3 Non-traceable author statement. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro unfolded protein binding Ref.3 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAQ	P27348	1	EBI-353655,EBI-359854

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75494-1)

Also known as: TASR-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 2 (identifier: O75494-2)

The sequence of this isoform differs from the canonical sequence as follows:
     147-147: Missing.

Isoform 3 (identifier: O75494-3)

Also known as: TASR-2; SRp38-2;

The sequence of this isoform differs from the canonical sequence as follows:
     165-183: FKHRNRSFSRSKSNSRSRS → PNCSWNTQYSSAYYTSRKI
     184-262: Missing.

Note: Phosphorylated on Ser-168 (By similarity).

Isoform 4 (identifier: O75494-4)

The sequence of this isoform differs from the canonical sequence as follows:
     164-173: RFKHRNRSFS → SQVSKKKNER
     174-262: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 262	262	FUS-interacting serine-arginine-rich protein 1		PRO_0000081593
Regions
	Domain	10 – 88	79	RRM
	Compositional bias	106 – 260	155	Arg/Ser-rich (RS domain)
Amino acid modifications
	Modified residue	110	1	Phosphotyrosine Ref.11
	Modified residue	129	1	Phosphoserine Ref.11 Ref.12 Ref.14
	Modified residue	131	1	Phosphoserine Ref.11 Ref.12 Ref.14 Ref.13
	Modified residue	133	1	Phosphoserine Ref.11 Ref.12 Ref.14 Ref.13 Ref.10
	Modified residue	156	1	Phosphoserine Ref.11
	Modified residue	158	1	Phosphoserine Ref.11
	Modified residue	160	1	Phosphoserine Ref.11
	Modified residue	235	1	Phosphoserine Ref.11
	Modified residue	251	1	Phosphoserine Ref.11
	Modified residue	253	1	Phosphoserine Ref.11
	Modified residue	255	1	Phosphothreonine Ref.11
	Modified residue	256	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	147	1	Missing in isoform 2.		VSP_010421
	Alternative sequence	164 – 173	10	RFKHRNRSFS → SQVSKKKNER in isoform 4.		VSP_010422
	Alternative sequence	165 – 183	19	FKHRN…SRSRS → PNCSWNTQYSSAYYTSRKI in isoform 3.		VSP_010424
	Alternative sequence	174 – 262	89	Missing in isoform 4.		VSP_010423
	Alternative sequence	184 – 262	79	Missing in isoform 3.		VSP_010425

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TASR-1) [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 205F95D36CBBFAB4	FASTA	262	31,301
	10 20 30 40 50 60 MSRYLRPPNT SLFVRNVADD TRSEDLRREF GRYGPIVDVY VPLDFYTRRP RGFAYVQFED 70 80 90 100 110 120 VRDAEDALHN LDRKWICGRQ IEIQFAQGDR KTPNQMKAKE GRNVYSSSRY DDYDRYRRSR 130 140 150 160 170 180 SRSYERRRSR SRSFDYNYRR SYSPRNSRPT GRPRRSRSHS DNDRFKHRNR SFSRSKSNSR 190 200 210 220 230 240 SRSKSQPKKE MKAKSRSRSA SHTKTRGTSK TDSKTHYKSG SRYEKESRKK EPPRSKSQSR 250 260 SQSRSRSKSR SRSWTSPKSS GH
	Isoform 2. Checksum: A07499B11D4C7570	FASTA	261	31,213
	10 20 30 40 50 60 MSRYLRPPNT SLFVRNVADD TRSEDLRREF GRYGPIVDVY VPLDFYTRRP RGFAYVQFED 70 80 90 100 110 120 VRDAEDALHN LDRKWICGRQ IEIQFAQGDR KTPNQMKAKE GRNVYSSSRY DDYDRYRRSR 130 140 150 160 170 180 SRSYERRRSR SRSFDYNYRR SYSPRNRPTG RPRRSRSHSD NDRFKHRNRS FSRSKSNSRS 190 200 210 220 230 240 RSKSQPKKEM KAKSRSRSAS HTKTRGTSKT DSKTHYKSGS RYEKESRKKE PPRSKSQSRS 250 260 QSRSRSKSRS RSWTSPKSSG H
	Isoform 3 (TASR-2) (SRp38-2). Checksum: 4AA87CAA9B51A131	FASTA	183	22,222
	10 20 30 40 50 60 MSRYLRPPNT SLFVRNVADD TRSEDLRREF GRYGPIVDVY VPLDFYTRRP RGFAYVQFED 70 80 90 100 110 120 VRDAEDALHN LDRKWICGRQ IEIQFAQGDR KTPNQMKAKE GRNVYSSSRY DDYDRYRRSR 130 140 150 160 170 180 SRSYERRRSR SRSFDYNYRR SYSPRNSRPT GRPRRSRSHS DNDRPNCSWN TQYSSAYYTS RKI
	Isoform 4. Checksum: 4AB40FBF24846495	FASTA	173	21,000
	10 20 30 40 50 60 MSRYLRPPNT SLFVRNVADD TRSEDLRREF GRYGPIVDVY VPLDFYTRRP RGFAYVQFED 70 80 90 100 110 120 VRDAEDALHN LDRKWICGRQ IEIQFAQGDR KTPNQMKAKE GRNVYSSSRY DDYDRYRRSR 130 140 150 160 170 SRSYERRRSR SRSFDYNYRR SYSPRNSRPT GRPRRSRSHS DNDSQVSKKK NER

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH FUS. Tissue: Leukemia.
[2]	"TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins." Yang L., Embree L.J., Hickstein D.D. Mol. Cell. Biol. 20:3345-3354(2000) [PubMed: 10779324] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing." Cowper A.E., Caceres J.F., Mayeda A., Screaton G.R. J. Biol. Chem. 276:48908-48914(2001) [PubMed: 11684676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"The SR protein SRp38 represses splicing in M Phase cells." Shin C., Manley J.L. Cell 111:407-417(2002) [PubMed: 12419250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), FUNCTION, PHOSPHORYLATION.
[5]	"Characterization and expression of the human gene encoding two translocation liposarcoma protein-associated serine-arginine (TASR) proteins." Clinton J.M., Chansky H.A., Odell D.D., Zielinska-Kwiatkowska A., Hickstein D.D., Yang L. Gene 284:141-147(2002) [PubMed: 11891055] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING (ISOFORMS 2 AND 3), TISSUE SPECIFICITY.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORMS 1 AND 3). Tissue: Muscle, Placenta and Uterus.
[9]	"Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock." Shin C., Feng Y., Manley J.L. Nature 427:553-558(2004) [PubMed: 14765198] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH SNRNP70 AND TRA2B.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-110; SER-129; SER-131; SER-133; SER-156; SER-158; SER-160; SER-235; SER-251; SER-253; THR-255 AND SER-256, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129; SER-131 AND SER-133, MASS SPECTROMETRY.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131 AND SER-133, MASS SPECTROMETRY.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129; SER-131 AND SER-133, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF047448 mRNA. Translation: AAC70918.1. AF067730 mRNA. Translation: AAC26727.1. AF449427 mRNA. Translation: AAL57514.1. AY150180 mRNA. Translation: AAN65380.1. AY150181 mRNA. Translation: AAN65381.1. AF419331 mRNA. Translation: AAL16665.1. AF419332 Genomic DNA. Translation: AAL16666.1. AY048592 Genomic DNA. Translation: AAL06098.1. AY048592 Genomic DNA. Translation: AAL06099.1. AK001286 mRNA. Translation: BAA91601.1. AL590609 Genomic DNA. Translation: CAI14803.1. AL590609 Genomic DNA. Translation: CAI14805.1. AL590609 Genomic DNA. Translation: CAI14808.1. BC001107 mRNA. Translation: AAH01107.1. BC005039 mRNA. Translation: AAH05039.1. BC010074 mRNA. Translation: AAH10074.1.
IPI	IPI00009071. IPI00074587. IPI00386662. IPI00412643.
RefSeq	NP_006616.1. NP_473357.1. XP_001714010.1.
UniGene	Hs.3530 Hs.652334
3D structure databases
HSSP	HSSP built from PDB template 1CVJ based on UniProtKB P11940.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75494. 3 interactions.
PTM databases
PhosphoSite	O75494.
Proteomic databases
PRIDE	O75494.
Genome annotation databases
Ensembl	ENSG00000188529. Homo sapiens. [Contig view] ENSG00000215699. Homo sapiens. [Contig view]
GeneID	10772. 642558.
KEGG	hsa:10772. hsa:642558.
UCSC	uc009vqx.1. human. uc009vra.1. human.
Organism-specific databases
GeneCards	GC01M024163. GC01M024164. GC01M7J0036.
H-InvDB	HIX0000259. HIX0017648.
HGNC	HGNC:16713. FUSIP1.
MIM	605221. gene.
PharmGKB	PA28427.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O75494.
OMA	O75494. HEEDETR.
Gene expression databases
ArrayExpress	O75494.
Bgee	O75494.
GermOnline	ENSG00000188529. Homo sapiens.
Family and domain databases
InterPro	IPR012677. a_b_plait_nuc_bd. IPR000504. RRM_RNP1. [Graphical view]
Gene3D	G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.
Pfam	PF00076. RRM_1. 1 hit. [Graphical view]
SMART	SM00360. RRM. 1 hit. [Graphical view]
PROSITE	PS50102. RRM. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	40903.
SOURCE	Search...

Entry information

Entry name

FUSIP_HUMAN

Accession

Primary (citable) accession number: O75494
Secondary accession number(s): A6NFM6 , A6NI42, A6NIU7, O60572, Q5JRH9, Q5JRI2, Q5JRI4, Q96G09, Q96P17

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	November 1, 1998
Last modified:	July 7, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)