SREK1_HUMAN
ID SREK1_HUMAN Reviewed; 508 AA.
AC Q8WXA9; A4FTW3; Q2M1J0; Q86X37;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Splicing regulatory glutamine/lysine-rich protein 1;
DE AltName: Full=Serine/arginine-rich-splicing regulatory protein 86;
DE Short=SRrp86;
DE AltName: Full=Splicing factor, arginine/serine-rich 12;
DE AltName: Full=Splicing regulatory protein 508;
DE Short=SRrp508;
GN Name=SREK1; Synonyms=SFRS12, SRRP86;
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] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=12043562;
RA Zhang D.L., Sun X.J., Ling L.J., Chen R.S., Ma D.L.;
RT "Molecular cloning, characterization, chromosomal assignment, genomic
RT organization and verification of SFRS12(SRrp508), a novel member of human
RT SR protein superfamily and a human homolog of rat SRrp86.";
RL Yi Chuan Xue Bao 29:377-383(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Mammary gland, and Testis;
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 [3]
RP PARTIAL PROTEIN SEQUENCE, INTERACTION WITH THE SPLICEOSOME, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12176931; DOI=10.1101/gr.473902;
RA Rappsilber J., Ryder U., Lamond A.I., Mann M.;
RT "Large-scale proteomic analysis of the human spliceosome.";
RL Genome Res. 12:1231-1245(2002).
RN [4]
RP INTERACTION WITH SREK1IP1.
RX PubMed=15456940; DOI=10.1385/jmn:24:2:269;
RA Heese K., Fujita M., Akatsu H., Yamamoto T., Kosaka K., Nagai Y.,
RA Sawada T.;
RT "The splicing regulatory protein p18SRP is down-regulated in Alzheimer's
RT disease brain.";
RL J. Mol. Neurosci. 24:269-276(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171; SER-184 AND THR-363, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-504, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Participates in the regulation of alternative splicing by
CC modulating the activity of other splice facors. Inhibits the splicing
CC activity of SFRS1, SFRS2 and SFRS6. Augments the splicing activity of
CC SFRS3 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Binds SFRS1, SFRS2, SFRS3 and SFRS6. Interacts with
CC the spliceosome (By similarity). Interacts with SREK1IP1. {ECO:0000250,
CC ECO:0000269|PubMed:12176931, ECO:0000269|PubMed:15456940}.
CC -!- INTERACTION:
CC Q8WXA9; A0A0C4DG62: ARL6IP4; NbExp=3; IntAct=EBI-1044237, EBI-12248874;
CC Q8WXA9; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-1044237, EBI-473189;
CC Q8WXA9; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-1044237, EBI-5280197;
CC Q8WXA9; Q14498: RBM39; NbExp=3; IntAct=EBI-1044237, EBI-395290;
CC Q8WXA9; Q96SB4: SRPK1; NbExp=2; IntAct=EBI-1044237, EBI-539478;
CC Q8WXA9; P78362: SRPK2; NbExp=2; IntAct=EBI-1044237, EBI-593303;
CC Q8WXA9; Q05519: SRSF11; NbExp=3; IntAct=EBI-1044237, EBI-1051785;
CC Q8WXA9; Q05519-2: SRSF11; NbExp=6; IntAct=EBI-1044237, EBI-11975029;
CC Q8WXA9; P40222: TXLNA; NbExp=3; IntAct=EBI-1044237, EBI-359793;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WXA9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WXA9-2; Sequence=VSP_008399;
CC -!- SIMILARITY: Belongs to the splicing factor SR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47322.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AF459094; AAL67778.1; -; mRNA.
DR EMBL; BC047322; AAH47322.1; ALT_SEQ; mRNA.
DR EMBL; BC067770; AAH67770.1; -; mRNA.
DR EMBL; BC112343; AAI12344.1; -; mRNA.
DR CCDS; CCDS3991.1; -. [Q8WXA9-1]
DR CCDS; CCDS43323.1; -. [Q8WXA9-2]
DR RefSeq; NP_001070667.1; NM_001077199.2. [Q8WXA9-2]
DR RefSeq; NP_001257421.1; NM_001270492.1.
DR RefSeq; NP_001310456.1; NM_001323527.1. [Q8WXA9-1]
DR RefSeq; NP_631907.1; NM_139168.3. [Q8WXA9-1]
DR RefSeq; XP_011541473.1; XM_011543171.2. [Q8WXA9-1]
DR AlphaFoldDB; Q8WXA9; -.
DR SMR; Q8WXA9; -.
DR BioGRID; 126754; 194.
DR IntAct; Q8WXA9; 34.
DR MINT; Q8WXA9; -.
DR STRING; 9606.ENSP00000334538; -.
DR GlyGen; Q8WXA9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WXA9; -.
DR PhosphoSitePlus; Q8WXA9; -.
DR SwissPalm; Q8WXA9; -.
DR BioMuta; SREK1; -.
DR DMDM; 37537968; -.
DR EPD; Q8WXA9; -.
DR jPOST; Q8WXA9; -.
DR MassIVE; Q8WXA9; -.
DR MaxQB; Q8WXA9; -.
DR PaxDb; Q8WXA9; -.
DR PeptideAtlas; Q8WXA9; -.
DR PRIDE; Q8WXA9; -.
DR ProteomicsDB; 74999; -. [Q8WXA9-1]
DR ProteomicsDB; 75000; -. [Q8WXA9-2]
DR Antibodypedia; 23829; 95 antibodies from 21 providers.
DR DNASU; 140890; -.
DR Ensembl; ENST00000334121.11; ENSP00000334538.6; ENSG00000153914.16. [Q8WXA9-2]
DR Ensembl; ENST00000380918.7; ENSP00000370305.3; ENSG00000153914.16. [Q8WXA9-1]
DR GeneID; 140890; -.
DR KEGG; hsa:140890; -.
DR MANE-Select; ENST00000334121.11; ENSP00000334538.6; NM_001077199.3; NP_001070667.1. [Q8WXA9-2]
DR UCSC; uc003jun.5; human. [Q8WXA9-1]
DR CTD; 140890; -.
DR DisGeNET; 140890; -.
DR GeneCards; SREK1; -.
DR HGNC; HGNC:17882; SREK1.
DR HPA; ENSG00000153914; Low tissue specificity.
DR MIM; 609268; gene.
DR neXtProt; NX_Q8WXA9; -.
DR OpenTargets; ENSG00000153914; -.
DR PharmGKB; PA38255; -.
DR VEuPathDB; HostDB:ENSG00000153914; -.
DR eggNOG; KOG4676; Eukaryota.
DR GeneTree; ENSGT00730000110872; -.
DR HOGENOM; CLU_030029_2_0_1; -.
DR InParanoid; Q8WXA9; -.
DR OMA; QTSVIHA; -.
DR OrthoDB; 1460556at2759; -.
DR PhylomeDB; Q8WXA9; -.
DR TreeFam; TF106266; -.
DR PathwayCommons; Q8WXA9; -.
DR SignaLink; Q8WXA9; -.
DR BioGRID-ORCS; 140890; 145 hits in 1086 CRISPR screens.
DR ChiTaRS; SREK1; human.
DR GeneWiki; SFRS12; -.
DR GenomeRNAi; 140890; -.
DR Pharos; Q8WXA9; Tbio.
DR PRO; PR:Q8WXA9; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8WXA9; protein.
DR Bgee; ENSG00000153914; Expressed in sural nerve and 206 other tissues.
DR ExpressionAtlas; Q8WXA9; baseline and differential.
DR Genevisible; Q8WXA9; HS.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd12260; RRM2_SREK1; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR034192; SREK1_RRM2.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Isopeptide bond;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; Spliceosome; Ubl conjugation.
FT CHAIN 1..508
FT /note="Splicing regulatory glutamine/lysine-rich protein 1"
FT /id="PRO_0000081940"
FT DOMAIN 66..142
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 173..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..258
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..365
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..408
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..486
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..508
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 363
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 504
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1
FT /note="M -> MNSGGGFGLGLGFGLTPTSVIQVTNLSSAVTSEQMRTLFSFLGEIEE
FT LRLYPPDNAPLAFSSKVCYVKFRDPSSVGVAQHLTNTVFIDRALIVVPCAEGKIPEESK
FT ALSLLAPAPTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008399"
SQ SEQUENCE 508 AA; 59380 MW; 878DC088B642EC3F CRC64;
MTSLMPGAGL LPIPTPNPLT TLGVSLSSLG AIPAAALDPN IATLGEIPQP PLMGNVDPSK
IDEIRRTVYV GNLNSQTTTA DQLLEFFKQV GEVKFVRMAG DETQPTRFAF VEFADQNSVP
RALAFNGVMF GDRPLKINHS NNAIVKPPEM TPQAAAKELE EVMKRVREAQ SFISAAIEPE
SGKSNERKGG RSRSHTRSKS RSSSKSHSRR KRSQSKHRSR SHNRSRSRQK DRRRSKSPHK
KRSKSRERRK SRSRSHSRDK RKDTREKIKE KERVKEKDRE KEREREKERE KEKERGKNKD
RDKEREKDRE KDKEKDRERE REKEHEKDRD KEKEKEQDKE KEREKDRSKE IDEKRKKDKK
SRTPPRSYNA SRRSRSSSRE RRRRRSRSSS RSPRTSKTIK RKSSRSPSPR SRNKKDKKRE
KERDHISERR ERERSTSMRK SSNDRDGKEK LEKNSTSLKE KEHNKEPDSS VSKEVDDKDA
PRTEENKIQH NGNCQLNEEN LSTKTEAV