Q08170 (SRSF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/arginine-rich splicing factor 4

Alternative name(s):
Pre-mRNA-splicing factor SRP75
SRP001LB
Splicing factor, arginine/serine-rich 4

Gene names

Name:	SRSF4
Synonyms:	SFRS4, SRP75

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	494 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in alternative splice site selection during pre-mRNA splicing. Represses the splicing of MAPT/Tau exon 10. Ref.8
Subunit structure	Found in a pre-mRNA splicing complex with SRSF4/SFRS4, SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Interacts with PNN. Ref.7 Ref.9
Subcellular location	Nucleus speckle Ref.9.
Post-translational modification	Extensively phosphorylated on serine residues in the RS domain.
Sequence similarities	Belongs to the splicing factor SR family. Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	RNA-binding
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	mRNA 3'-end processing Traceable author statement. Source: Reactome mRNA export from nucleus Traceable author statement. Source: Reactome mRNA splicing, via spliceosome Traceable author statement. Source: Reactome negative regulation of mRNA splicing, via spliceosome Inferred from direct assay Ref.8. Source: UniProtKB termination of RNA polymerase II transcription Traceable author statement. Source: Reactome
Cellular_component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 494	494	Serine/arginine-rich splicing factor 4		PRO_0000081925
Regions
	Domain	2 – 72	71	RRM 1
	Domain	104 – 177	74	RRM 2
	Compositional bias	72 – 97	26	Gly-rich (hinge region)
	Compositional bias	179 – 494	316	Arg/Ser-rich (RS domain)
Amino acid modifications
	Modified residue	78	1	Phosphoserine Ref.11
	Modified residue	316	1	Phosphoserine Ref.13
	Modified residue	318	1	Phosphoserine Ref.13
	Modified residue	431	1	Phosphoserine Ref.11 Ref.13
Natural variations
	Natural variant	253	1	E → D. Ref.1 Corresponds to variant rs2230679 [ dbSNP | Ensembl ].		VAR_052230
	Natural variant	338	1	G → A. Ref.1 Corresponds to variant rs2230677 [ dbSNP | Ensembl ].		VAR_052231
	Natural variant	356	1	G → S. Ref.1 Corresponds to variant rs2230678 [ dbSNP | Ensembl ].		VAR_052232
	Natural variant	438	1	Q → E. Corresponds to variant rs1049928 [ dbSNP | Ensembl ].		VAR_052233
Experimental info
	Sequence conflict	35	1	N → D AA sequence Ref.6
	Sequence conflict	318 – 322	5	SRGRS → EQGQE in AAA36649. Ref.1
	Sequence conflict	436 – 438	3	TNQ → RNE in AAA36649. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q08170 [UniParc]. Last modified May 15, 2002. Version 2. Checksum: 5BBAB917C218C20A	FASTA	494	56,678
	10 20 30 40 50 60 MPRVYIGRLS YQARERDVER FFKGYGKILE VDLKNGYGFV EFDDLRDADD AVYELNGKDL 70 80 90 100 110 120 CGERVIVEHA RGPRRDGSYG SGRSGYGYRR SGRDKYGPPT RTEYRLIVEN LSSRCSWQDL 130 140 150 160 170 180 KDYMRQAGEV TYADAHKGRK NEGVIEFVSY SDMKRALEKL DGTEVNGRKI RLVEDKPGSR 190 200 210 220 230 240 RRRSYSRSRS HSRSRSRSRH SRKSRSRSGS SKSSHSKSRS RSRSGSRSRS KSRSRSQSRS 250 260 270 280 290 300 RSKKEKSRSP SKEKSRSRSH SAGKSRSKSK DQAEEKIQNN DNVGKPKSRS PSRHKSKSKS 310 320 330 340 350 360 RSRSQERRVE EEKRGSVSRG RSQEKSLRQS RSRSRSKGGS RSRSRSRSKS KDKRKGRKRS 370 380 390 400 410 420 REESRSRSRS RSKSERSRKR GSKRDSKAGS SKKKKKEDTD RSQSRSPSRS VSKEREHAKS 430 440 450 460 470 480 ESSQREGRGE SENAGTNQET RSRSRSNSKS KPNLPSESRS RSKSASKTRS RSKSRSRSAS 490 RSPSRSRSRS HSRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human SR proteins and isolation of a cDNA encoding SRp75." Zahler A.M., Neugebauer K.M., Stolk J.A., Roth M.B. Mol. Cell. Biol. 13:4023-4028(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANTS ASP-253; ALA-338 AND SER-356.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[5]	"Sequencing of human chromosome 1." Connolly K.S., Gunning K.M., Davis C.A., Kadner K., Subramanian S., Miguel T., Lewis K.D., Fridlyand J., Alcivare D., Benke J.A., Bondoc M., Bowen E., Chiang A., Critz P., Jaklevic M.A., Lindo K., Lindquist K., Miller C. , Patel S., Piscia C., Riley B.E., Rojeski H., Sarmiento R., Yu C., Montenegro M., Aerts A., Chung A., Abrajano A., Baker M., Gau C., Jett J., Ko C., Beall K., Woolley J.P., Conboy J., Fang J.F., Narla M., Stultz J.L., Kimmerly W., Martin C.H. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-192.
[6]	"SR proteins: a conserved family of pre-mRNA splicing factors." Zahler A.M., Lane W.S., Stolk J.A., Roth M.B. Genes Dev. 6:837-847(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 35-45; 84-89; 126-137; 140-154 AND 172-179.
[7]	"A coactivator of pre-mRNA splicing." Blencowe B.J., Issner R., Nickerson J.A., Sharp P.A. Genes Dev. 12:996-1009(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A MRNA SPLICING COMPLEX WITH SRSF5; SNRNP70; SNRPA1; SRRM1 AND SRRM2.
[8]	"Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors." Wang J., Gao Q.S., Wang Y., Lafyatis R., Stamm S., Andreadis A. J. Neurochem. 88:1078-1090(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal epithelial cells." Zimowska G., Shi J., Munguba G., Jackson M.R., Alpatov R., Simmons M.N., Shi Y., Sugrue S.P. Invest. Ophthalmol. Vis. Sci. 44:4715-4723(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PNN, SUBCELLULAR LOCATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-431, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316; SER-318 AND SER-431, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L14076 mRNA. Translation: AAA36649.1. BT007415 mRNA. Translation: AAP36083.1. AL590729, AL357500 Genomic DNA. Translation: CAI14326.1. AL357500, AL590729 Genomic DNA. Translation: CAH71635.1. BC002781 mRNA. Translation: AAH02781.1. AC004236 Genomic DNA. Translation: AAC04476.1.
IPI	IPI00000015.
PIR	A48133.
RefSeq	NP_005617.2. NM_005626.4.
UniGene	Hs.469970.
3D structure databases
ProteinModelPortal	Q08170.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q08170. 10 interactions.
MINT	MINT-1410521.
PTM databases
PhosphoSite	Q08170.
Polymorphism databases
DMDM	20981726.
Proteomic databases
PaxDb	Q08170.
PeptideAtlas	Q08170.
PRIDE	Q08170.
Protocols and materials databases
DNASU	6429.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373795; ENSP00000362900; ENSG00000116350.
GeneID	6429.
KEGG	hsa:6429.
UCSC	uc001bro.3. human.
Organism-specific databases
CTD	6429.
GeneCards	GC01M029474.
H-InvDB	HIX0160019.
HGNC	HGNC:10786. SRSF4.
HPA	HPA050975.
MIM	601940. gene.
neXtProt	NX_Q08170.
PharmGKB	PA35702.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0724.
HOVERGEN	HBG002295.
InParanoid	Q08170.
KO	K12893.
OMA	REHAKSE.
OrthoDB	EOG41C6X9.
PhylomeDB	Q08170.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_1788. Transcription. REACT_71. Gene Expression. REACT_78. Post-Elongation Processing of the Transcript.
Gene expression databases
ArrayExpress	Q08170.
Bgee	Q08170.
CleanEx	HS_SFRS4.
Genevestigator	Q08170.
GermOnline	ENSG00000116350. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.330. 2 hits.
InterPro	IPR012677. Nucleotide-bd_a/b_plait. IPR000504. RRM_dom. [Graphical view]
Pfam	PF00076. RRM_1. 2 hits. [Graphical view]
SMART	SM00360. RRM. 2 hits. [Graphical view]
PROSITE	PS50102. RRM. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SRSF4. human.
GenomeRNAi	6429.
NextBio	24969.
SOURCE	Search...

Entry information

Entry name

SRSF4_HUMAN

Accession

Primary (citable) accession number: Q08170
Secondary accession number(s): Q5VXP1, Q9BUA4, Q9UEB5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	May 15, 2002
Last modified:	May 29, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.