SRPK2_MOUSE
ID SRPK2_MOUSE Reviewed; 681 AA.
AC O54781; Q8VCD9;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=SRSF protein kinase 2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:9446799};
DE AltName: Full=SFRS protein kinase 2;
DE AltName: Full=Serine/arginine-rich protein-specific kinase 2;
DE Short=SR-protein-specific kinase 2;
DE Contains:
DE RecName: Full=SRSF protein kinase 2 N-terminal;
DE Contains:
DE RecName: Full=SRSF protein kinase 2 C-terminal;
GN Name=Srpk2 {ECO:0000312|MGI:MGI:1201408};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA24055.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain {ECO:0000269|PubMed:9446799};
RX PubMed=9446799; DOI=10.1006/bbrc.1997.7913;
RA Kuroyanagi N., Onogi H., Wakabayashi T., Hagiwara M.;
RT "Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles.";
RL Biochem. Biophys. Res. Commun. 242:357-364(1998).
RN [2] {ECO:0000312|EMBL:AAH20178.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye {ECO:0000312|EMBL:AAH20178.1};
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 INTERACTION WITH ACIN1.
RX PubMed=18559500; DOI=10.1158/0008-5472.can-08-0021;
RA Jang S.W., Yang S.J., Ehlen A., Dong S., Khoury H., Chen J., Persson J.L.,
RA Ye K.;
RT "Serine/arginine protein-specific kinase 2 promotes leukemia cell
RT proliferation by phosphorylating acinus and regulating cyclin A1.";
RL Cancer Res. 68:4559-4570(2008).
RN [4]
RP FUNCTION.
RX PubMed=19592491; DOI=10.1074/jbc.m109.026237;
RA Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.;
RT "Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle
RT and cell death in neurons.";
RL J. Biol. Chem. 284:24512-24525(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; THR-331; THR-332;
RP SER-378; SER-468; THR-471; SER-477; SER-479; SER-483 AND SER-487, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine/arginine-rich protein-specific kinase which
CC specifically phosphorylates its substrates at serine residues located
CC in regions rich in arginine/serine dipeptides, known as RS domains and
CC is involved in the phosphorylation of SR splicing factors and the
CC regulation of splicing (PubMed:9446799). Promotes neuronal apoptosis by
CC up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). This is
CC done by the phosphorylation of SRSF2, leading to the suppression of
CC p53/TP53 phosphorylation thereby relieving the repressive effect of
CC p53/TP53 on cyclin-D1 (CCND1) expression (By similarity).
CC Phosphorylates ACIN1, and redistributes it from the nuclear speckles to
CC the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation
CC (By similarity). Plays an essential role in spliceosomal B complex
CC formation via the phosphorylation of DDX23/PRP28 (By similarity).
CC Probably by phosphorylating DDX23, leads to the suppression of
CC incorrect R-loops formed during transcription; R-loops are composed of
CC a DNA:RNA hybrid and the associated non-template single-stranded DNA
CC (By similarity). {ECO:0000250|UniProtKB:P78362,
CC ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:9446799}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:9446799};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:9446799};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9446799};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Ser-50 and Ser-
CC 581. {ECO:0000250|UniProtKB:Q96SB4}.
CC -!- SUBUNIT: Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins
CC (U4/U6-U5 tri-snRNPs) (By similarity). Interacts with PKB/AKT1 in a
CC phosphorylation-dependent manner (By similarity). The phosphorylated
CC form (by PKB/AKT1) interacts with YWHAB and YWHAE (By similarity).
CC Interaction with YWHAB suppresses its cleavage by caspases and inhibits
CC the release of its N-terminal pro-apoptotic fragment (By similarity).
CC Interacts with SFN (By similarity). Interacts with ACIN1
CC (PubMed:18559500). Interacts with POLR2A/RNA polymerase II; the
CC interaction occurs during the co-transcriptional formation of
CC inappropriate R-loops (By similarity). {ECO:0000250|UniProtKB:P78362,
CC ECO:0000269|PubMed:18559500}.
CC -!- INTERACTION:
CC O54781; Q07955: SRSF1; Xeno; NbExp=3; IntAct=EBI-593325, EBI-398920;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9446799}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:9446799}. Nucleus speckle
CC {ECO:0000250|UniProtKB:P78362}. Chromosome
CC {ECO:0000250|UniProtKB:P78362}. Note=Shuttles between the nucleus and
CC the cytoplasm (By similarity). KAT5/TIP60 inhibits its nuclear
CC translocation (By similarity). Phosphorylation at Thr-492 by PKB/AKT1
CC promotes nuclear translocation (By similarity). Preferentially
CC localizes across the entire gene coding region (By similarity). During
CC transcription, accumulates at chromatin loci where unscheduled R-loops
CC form and colocalizes with paused 'Ser-5'-phosphorlyated POLR2A/RNA
CC polymerase II and helicase DDX23 (By similarity).
CC {ECO:0000250|UniProtKB:P78362}.
CC -!- TISSUE SPECIFICITY: Expressed in testes, lung and brain.
CC {ECO:0000269|PubMed:9446799}.
CC -!- PTM: Phosphorylation at Thr-485 by PKB/AKT1 enhances its stimulatory
CC activity in triggering cyclin-D1 (CCND1) expression and promoting
CC apoptosis in neurons, which can be blocked by YWHAB. It also enhances
CC its protein kinase activity toward ACIN1 and SRSF2, promotes its
CC nuclear translocation and prevents its proteolytic cleavage (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved at Asp-137 and Asp-401 by caspase-3 during
CC apoptotic cell death. Cleavage at Asp-137 which is the major site of
CC cleavage, produces a small N-terminal fragment that translocates into
CC nucleus and promotes VP16-induced apoptosis (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB006036; BAA24055.1; -; mRNA.
DR EMBL; BC020178; AAH20178.1; -; mRNA.
DR PIR; JC5929; JC5929.
DR RefSeq; NP_033300.2; NM_009274.2.
DR RefSeq; XP_017176258.1; XM_017320769.1.
DR AlphaFoldDB; O54781; -.
DR SMR; O54781; -.
DR BioGRID; 203503; 24.
DR IntAct; O54781; 6.
DR MINT; O54781; -.
DR STRING; 10090.ENSMUSP00000085734; -.
DR iPTMnet; O54781; -.
DR PhosphoSitePlus; O54781; -.
DR EPD; O54781; -.
DR MaxQB; O54781; -.
DR PaxDb; O54781; -.
DR PeptideAtlas; O54781; -.
DR PRIDE; O54781; -.
DR ProteomicsDB; 257402; -.
DR DNASU; 20817; -.
DR GeneID; 20817; -.
DR KEGG; mmu:20817; -.
DR UCSC; uc008wqe.1; mouse.
DR CTD; 6733; -.
DR MGI; MGI:1201408; Srpk2.
DR eggNOG; KOG1290; Eukaryota.
DR InParanoid; O54781; -.
DR OrthoDB; 290680at2759; -.
DR PhylomeDB; O54781; -.
DR TreeFam; TF105334; -.
DR BioGRID-ORCS; 20817; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Srpk2; mouse.
DR PRO; PR:O54781; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O54781; protein.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IDA:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISS:BHF-UCL.
DR GO; GO:0035063; P:nuclear speck organization; IDA:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:BHF-UCL.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISS:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0062176; P:R-loop disassembly; ISS:UniProtKB.
DR GO; GO:0050684; P:regulation of mRNA processing; IBA:GO_Central.
DR GO; GO:0008380; P:RNA splicing; IDA:UniProtKB.
DR GO; GO:0000245; P:spliceosomal complex assembly; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chromosome; Cytoplasm; Differentiation; Kinase;
KW mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..681
FT /note="SRSF protein kinase 2"
FT /id="PRO_0000086678"
FT CHAIN 1..137
FT /note="SRSF protein kinase 2 N-terminal"
FT /id="PRO_0000414753"
FT CHAIN 138..681
FT /note="SRSF protein kinase 2 C-terminal"
FT /id="PRO_0000414754"
FT DOMAIN 79..681
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 302..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..43
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..58
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..368
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..417
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..496
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 212
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 85..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 137..138
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT SITE 401..402
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 331
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 332
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 471
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 485
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:P78362"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78362"
FT MOD_RES 581
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250"
FT CONFLICT 313
FT /note="Q -> QQ (in Ref. 2; AAH20178)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="L -> P (in Ref. 1; BAA24055)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 681 AA; 76757 MW; 1857EA955B2F9C0E CRC64;
MSVNSEKSSS SERPEPQQKA PLVPPPPPPP PPPPLPDPAP PEPEEEILGS DDEEQEDPAD
YCKGGYHPVK IGDLFNGRYH VIRKLGWGHF STVWLCWDMQ GKRFVAMKVV KSAQHYTETA
LDEIKLLKCV RESDPSDPNK DMVVQLIDDF KISGMNGIHV CMVFEVLGHH LLKWIIKSNY
QGLPVRCVKS IIRQVLQGLD YLHSKCKIIH TDIKPENILM CVDDAYVRRM AAEATEWQKA
GAPPPSGSAV STAPQQKPIG KISKNKKKKL KKKQKRQAEL LEKRLQEIEE LEREAERKIL
EENITSAEAS GEQDGEYQPE VTLKAADLED TTEEETAKDN GEVEDQEEKE DAEKENAEKD
EDDVEQELAN LDPTWVESPK ANGHIENGPF SLEQQLEDEE DDEDDCANPE EYNLDEPNAE
SDYTYSSSYE QFNGELPNGQ HKTSEFPTPL FSGPLEPVAC GSVISEGSPL TEQEESSPSH
DRSRTVSASS TGDLPKTKTR AADLLVNPLD PRNADKIRVK IADLGNACWV HKHFTEDIQT
RQYRSIEVLI GAGYSTPADI WSTACMAFEL ATGDYLFEPH SGEDYSRDED HIAHIIELLG
SIPRHFALSG KYSREFFNRR GELRHITKLK PWSLFDVLVE KYGWPHEDAA QFTDFLIPML
EMVPEKRASA GECLRHPWLN S
