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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
 
 
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