SRSF4_HUMAN
ID SRSF4_HUMAN Reviewed; 494 AA.
AC Q08170; Q5VXP1; Q9BUA4; Q9UEB5;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Serine/arginine-rich splicing factor 4;
DE AltName: Full=Pre-mRNA-splicing factor SRP75;
DE AltName: Full=SRP001LB;
DE AltName: Full=Splicing factor, arginine/serine-rich 4;
GN Name=SRSF4; Synonyms=SFRS4, SRP75;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANTS ASP-253;
RP ALA-338 AND SER-356.
RX PubMed=8321209; DOI=10.1128/mcb.13.7.4023-4028.1993;
RA Zahler A.M., Neugebauer K.M., Stolk J.A., Roth M.B.;
RT "Human SR proteins and isolation of a cDNA encoding SRp75.";
RL Mol. Cell. Biol. 13:4023-4028(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-192.
RA Connolly K.S., Gunning K.M., Davis C.A., Kadner K., Subramanian S.,
RA Miguel T., Lewis K.D., Fridlyand J., Alcivare D., Benke J.A., Bondoc M.,
RA Bowen E., Chiang A., Critz P., Jaklevic M.A., Lindo K., Lindquist K.,
RA Miller C., Patel S., Piscia C., Riley B.E., Rojeski H., Sarmiento R.,
RA Yu C., Montenegro M., Aerts A., Chung A., Abrajano A., Baker M., Gau C.,
RA Jett J., Ko C., Beall K., Woolley J.P., Conboy J., Fang J.F., Narla M.,
RA Stultz J.L., Kimmerly W., Martin C.H.;
RT "Sequencing of human chromosome 1.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 35-45; 84-89; 126-137; 140-154 AND 172-179.
RX PubMed=1577277; DOI=10.1101/gad.6.5.837;
RA Zahler A.M., Lane W.S., Stolk J.A., Roth M.B.;
RT "SR proteins: a conserved family of pre-mRNA splicing factors.";
RL Genes Dev. 6:837-847(1992).
RN [7]
RP IDENTIFICATION IN A MRNA SPLICING COMPLEX WITH SRSF5; SNRNP70; SNRPA1;
RP SRRM1 AND SRRM2.
RX PubMed=9531537; DOI=10.1101/gad.12.7.996;
RA Blencowe B.J., Issner R., Nickerson J.A., Sharp P.A.;
RT "A coactivator of pre-mRNA splicing.";
RL Genes Dev. 12:996-1009(1998).
RN [8]
RP FUNCTION.
RX PubMed=15009664; DOI=10.1046/j.1471-4159.2003.02232.x;
RA Wang J., Gao Q.S., Wang Y., Lafyatis R., Stamm S., Andreadis A.;
RT "Tau exon 10, whose missplicing causes frontotemporal dementia, is
RT regulated by an intricate interplay of cis elements and trans factors.";
RL J. Neurochem. 88:1078-1090(2004).
RN [9]
RP INTERACTION WITH PNN, AND SUBCELLULAR LOCATION.
RX PubMed=14578391; DOI=10.1167/iovs.03-0240;
RA Zimowska G., Shi J., Munguba G., Jackson M.R., Alpatov R., Simmons M.N.,
RA Shi Y., Sugrue S.P.;
RT "Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal
RT epithelial cells.";
RL Invest. Ophthalmol. Vis. Sci. 44:4715-4723(2003).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-431, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-288; SER-290;
RP SER-292; SER-456; SER-458 AND SER-460, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446 AND SER-458, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Plays a role in alternative splice site selection during pre-
CC mRNA splicing. Represses the splicing of MAPT/Tau exon 10.
CC {ECO:0000269|PubMed:15009664}.
CC -!- SUBUNIT: Found in a pre-mRNA splicing complex with SRSF4/SFRS4,
CC SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Interacts with PNN.
CC {ECO:0000269|PubMed:14578391, ECO:0000269|PubMed:9531537}.
CC -!- INTERACTION:
CC Q08170; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-722621, EBI-1055254;
CC Q08170; P62995: TRA2B; NbExp=4; IntAct=EBI-722621, EBI-725485;
CC Q08170; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-722621, EBI-10180829;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:14578391}.
CC -!- PTM: Extensively phosphorylated on serine residues in the RS domain.
CC -!- SIMILARITY: Belongs to the splicing factor SR family. {ECO:0000305}.
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DR EMBL; L14076; AAA36649.1; -; mRNA.
DR EMBL; BT007415; AAP36083.1; -; mRNA.
DR EMBL; AL590729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002781; AAH02781.1; -; mRNA.
DR EMBL; AC004236; AAC04476.1; -; Genomic_DNA.
DR CCDS; CCDS333.1; -.
DR PIR; A48133; A48133.
DR RefSeq; NP_005617.2; NM_005626.4.
DR AlphaFoldDB; Q08170; -.
DR SMR; Q08170; -.
DR BioGRID; 112327; 362.
DR CORUM; Q08170; -.
DR IntAct; Q08170; 42.
DR MINT; Q08170; -.
DR STRING; 9606.ENSP00000362900; -.
DR DrugBank; DB11638; Artenimol.
DR GlyGen; Q08170; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q08170; -.
DR PhosphoSitePlus; Q08170; -.
DR SwissPalm; Q08170; -.
DR BioMuta; SRSF4; -.
DR DMDM; 20981726; -.
DR EPD; Q08170; -.
DR jPOST; Q08170; -.
DR MassIVE; Q08170; -.
DR MaxQB; Q08170; -.
DR PaxDb; Q08170; -.
DR PeptideAtlas; Q08170; -.
DR PRIDE; Q08170; -.
DR ProteomicsDB; 58574; -.
DR Antibodypedia; 31007; 176 antibodies from 25 providers.
DR DNASU; 6429; -.
DR Ensembl; ENST00000373795.7; ENSP00000362900.4; ENSG00000116350.18.
DR GeneID; 6429; -.
DR KEGG; hsa:6429; -.
DR MANE-Select; ENST00000373795.7; ENSP00000362900.4; NM_005626.5; NP_005617.2.
DR UCSC; uc001bro.4; human.
DR CTD; 6429; -.
DR DisGeNET; 6429; -.
DR GeneCards; SRSF4; -.
DR HGNC; HGNC:10786; SRSF4.
DR HPA; ENSG00000116350; Low tissue specificity.
DR MIM; 601940; gene.
DR neXtProt; NX_Q08170; -.
DR OpenTargets; ENSG00000116350; -.
DR PharmGKB; PA35702; -.
DR VEuPathDB; HostDB:ENSG00000116350; -.
DR eggNOG; KOG0106; Eukaryota.
DR GeneTree; ENSGT00940000156213; -.
DR InParanoid; Q08170; -.
DR OMA; EAYSDHE; -.
DR OrthoDB; 1315388at2759; -.
DR PhylomeDB; Q08170; -.
DR TreeFam; TF351335; -.
DR PathwayCommons; Q08170; -.
DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR SignaLink; Q08170; -.
DR BioGRID-ORCS; 6429; 28 hits in 1077 CRISPR screens.
DR ChiTaRS; SRSF4; human.
DR GeneWiki; SFRS4; -.
DR GenomeRNAi; 6429; -.
DR Pharos; Q08170; Tbio.
DR PRO; PR:Q08170; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q08170; protein.
DR Bgee; ENSG00000116350; Expressed in sural nerve and 203 other tissues.
DR ExpressionAtlas; Q08170; baseline and differential.
DR Genevisible; Q08170; HS.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:1990825; F:sequence-specific mRNA binding; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0008380; P:RNA splicing; TAS:ProtInc.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; TAS:ProtInc.
DR CDD; cd12337; RRM1_SRSF4_like; 1.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR035585; RRM1_SRSF4-like.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 2.
DR SMART; SM00360; RRM; 2.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 2.
PE 1: Evidence at protein level;
KW Direct protein sequencing; mRNA processing; mRNA splicing; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Repressor; RNA-binding.
FT CHAIN 1..494
FT /note="Serine/arginine-rich splicing factor 4"
FT /id="PRO_0000081925"
FT DOMAIN 2..72
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 104..177
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 72..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..242
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..282
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..331
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..356
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..494
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 253
FT /note="E -> D (in dbSNP:rs2230679)"
FT /evidence="ECO:0000269|PubMed:8321209"
FT /id="VAR_052230"
FT VARIANT 338
FT /note="G -> A (in dbSNP:rs2230677)"
FT /evidence="ECO:0000269|PubMed:8321209"
FT /id="VAR_052231"
FT VARIANT 356
FT /note="G -> S (in dbSNP:rs2230678)"
FT /evidence="ECO:0000269|PubMed:8321209"
FT /id="VAR_052232"
FT VARIANT 438
FT /note="Q -> E (in dbSNP:rs1049928)"
FT /id="VAR_052233"
FT CONFLICT 35
FT /note="N -> D (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 318..322
FT /note="SRGRS -> EQGQE (in Ref. 1; AAA36649)"
FT /evidence="ECO:0000305"
FT CONFLICT 436..438
FT /note="TNQ -> RNE (in Ref. 1; AAA36649)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 494 AA; 56678 MW; 5BBAB917C218C20A CRC64;
MPRVYIGRLS YQARERDVER FFKGYGKILE VDLKNGYGFV EFDDLRDADD AVYELNGKDL
CGERVIVEHA RGPRRDGSYG SGRSGYGYRR SGRDKYGPPT RTEYRLIVEN LSSRCSWQDL
KDYMRQAGEV TYADAHKGRK NEGVIEFVSY SDMKRALEKL DGTEVNGRKI RLVEDKPGSR
RRRSYSRSRS HSRSRSRSRH SRKSRSRSGS SKSSHSKSRS RSRSGSRSRS KSRSRSQSRS
RSKKEKSRSP SKEKSRSRSH SAGKSRSKSK DQAEEKIQNN DNVGKPKSRS PSRHKSKSKS
RSRSQERRVE EEKRGSVSRG RSQEKSLRQS RSRSRSKGGS RSRSRSRSKS KDKRKGRKRS
REESRSRSRS RSKSERSRKR GSKRDSKAGS SKKKKKEDTD RSQSRSPSRS VSKEREHAKS
ESSQREGRGE SENAGTNQET RSRSRSNSKS KPNLPSESRS RSKSASKTRS RSKSRSRSAS
RSPSRSRSRS HSRS
