SRPK1_MOUSE
ID SRPK1_MOUSE Reviewed; 648 AA.
AC O70551; O70193; Q99JT3;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=SRSF protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=SFRS protein kinase 1;
DE AltName: Full=Serine/arginine-rich protein-specific kinase 1;
DE Short=SR-protein-specific kinase 1;
GN Name=Srpk1 {ECO:0000312|MGI:MGI:106908};
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:BAA25299.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
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:0000305, ECO:0000312|EMBL:CAA11833.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo {ECO:0000312|EMBL:CAA11833.1};
RX PubMed=10390541; DOI=10.1093/nar/27.14.2972;
RA Papoutsopoulou S., Nikolakaki E., Chalepakis G., Kruft V., Chevaillier P.,
RA Giannakouros T.;
RT "SR protein-specific kinase 1 is highly expressed in testis and
RT phosphorylates protamine 1.";
RL Nucleic Acids Res. 27:2972-2980(1999).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH05707.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH05707.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH05707.1}, and
RC Testis {ECO:0000312|EMBL:AAH50761.1};
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 [4]
RP PROTEIN SEQUENCE OF 573-581, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-309; SER-311; THR-448
RP AND SER-450, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-311; THR-448 AND
RP SER-450, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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. Plays a central role in the regulatory network
CC for splicing, controlling the intranuclear distribution of splicing
CC factors in interphase cells and the reorganization of nuclear speckles
CC during mitosis. Can influence additional steps of mRNA maturation, as
CC well as other cellular activities, such as chromatin reorganization in
CC somatic and sperm cells and cell cycle progression. Phosphorylates
CC SFRS2, ZRSR2, LBR and PRM1. Phosphorylates SRSF1 using a directional
CC (C-terminal to N-terminal) and a dual-track mechanism incorporating
CC both processive phosphorylation (in which the kinase stays attached to
CC the substrate after each round of phosphorylation) and distributive
CC phosphorylation steps (in which the kinase and substrate dissociate
CC after each phosphorylation event). The RS domain of SRSF1 binds first
CC to a docking groove in the large lobe of the kinase domain of SRPK1.
CC This induces certain structural changes in SRPK1 and/or RRM2 domain of
CC SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation.
CC The cycles continue for several phosphorylation steps in a processive
CC manner (steps 1-8) until the last few phosphorylation steps
CC (approximately steps 9-12). During that time, a mechanical stress
CC induces the unfolding of the beta-4 motif in RRM2, which then docks at
CC the docking groove of SRPK1. This also signals RRM2 to begin to
CC dissociate, which facilitates SRSF1 dissociation after phosphorylation
CC is completed. Can mediate hepatitis B virus (HBV) core protein
CC phosphorylation. It plays a negative role in the regulation of HBV
CC replication through a mechanism not involving the phosphorylation of
CC the core protein but by reducing the packaging efficiency of the
CC pregenomic RNA (pgRNA) without affecting the formation of the viral
CC core particles. Can induce splicing of exon 10 in MAPT/TAU (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:10390541,
CC 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:10390541, 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:10390541,
CC ECO:0000269|PubMed:9446799};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:9446799};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Ser-51 and Ser-
CC 548. {ECO:0000250|UniProtKB:Q96SB4}.
CC -!- SUBUNIT: Monomer. Found in a multisubunit complex containing seven
CC proteins, named toposome, which separates entangled circular chromatin
CC DNA during chromosome segregation. Interacts with HHV-1 ICP27 protein.
CC Interacts with DNAJC8 and AHSA1/AHA1 and this mediates formation of a
CC complex with the Hsp70 /Hsp90 machinery. Binds to IGF2BP1, SYNCRIP,
CC HNRNPA2B1 and HNRNPC. Interacts with SAFB/SAFB1 and SAFB2 which
CC inhibits its activity (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O70551; Q07955: SRSF1; Xeno; NbExp=5; IntAct=EBI-593343, EBI-398920;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96SB4}.
CC Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q96SB4}. Nucleus matrix
CC {ECO:0000250|UniProtKB:Q96SB4}. Microsome
CC {ECO:0000250|UniProtKB:Q96SB4}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q96SB4}. Chromosome
CC {ECO:0000250|UniProtKB:Q96SB4}. Note=Shuttles between the nucleus and
CC the cytoplasm (By similarity). Inhibition of the Hsp90 ATPase activity,
CC osmotic stress and interaction with HHV-1 ICP27 protein can induce its
CC translocation to the nucleus (By similarity). KAT5/TIP60 inhibits its
CC nuclear translocation (By similarity). Preferentially localizes to the
CC promoter of gene coding regions (By similarity).
CC {ECO:0000250|UniProtKB:Q96SB4}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the testis but is also
CC present at lower levels in heart, spleen, liver, brain, kidney, lung
CC and skeletal muscle. Present in all germinal cells in the seminiferous
CC tubules but not in mature spermatozoa. {ECO:0000269|PubMed:10390541,
CC ECO:0000269|PubMed:9446799}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AB012290; BAA25299.1; -; mRNA.
DR EMBL; AJ224115; CAA11833.1; -; mRNA.
DR EMBL; BC005707; AAH05707.1; -; mRNA.
DR EMBL; BC050761; AAH50761.1; -; mRNA.
DR CCDS; CCDS37531.1; -.
DR PIR; JC5930; JC5930.
DR RefSeq; NP_058075.2; NM_016795.4.
DR AlphaFoldDB; O70551; -.
DR SMR; O70551; -.
DR BioGRID; 203502; 1.
DR IntAct; O70551; 2.
DR STRING; 10090.ENSMUSP00000116259; -.
DR BindingDB; O70551; -.
DR ChEMBL; CHEMBL4105750; -.
DR iPTMnet; O70551; -.
DR PhosphoSitePlus; O70551; -.
DR EPD; O70551; -.
DR jPOST; O70551; -.
DR PaxDb; O70551; -.
DR PeptideAtlas; O70551; -.
DR PRIDE; O70551; -.
DR ProteomicsDB; 263346; -.
DR Antibodypedia; 6714; 482 antibodies from 32 providers.
DR DNASU; 20815; -.
DR Ensembl; ENSMUST00000130643; ENSMUSP00000116259; ENSMUSG00000004865.
DR GeneID; 20815; -.
DR KEGG; mmu:20815; -.
DR UCSC; uc008bri.1; mouse.
DR CTD; 6732; -.
DR MGI; MGI:106908; Srpk1.
DR VEuPathDB; HostDB:ENSMUSG00000004865; -.
DR eggNOG; KOG1290; Eukaryota.
DR GeneTree; ENSGT00940000155264; -.
DR HOGENOM; CLU_000288_81_9_1; -.
DR InParanoid; O70551; -.
DR OMA; HEGQRPP; -.
DR OrthoDB; 290680at2759; -.
DR PhylomeDB; O70551; -.
DR TreeFam; TF105334; -.
DR BioGRID-ORCS; 20815; 11 hits in 76 CRISPR screens.
DR ChiTaRS; Srpk1; mouse.
DR PRO; PR:O70551; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O70551; protein.
DR Bgee; ENSMUSG00000004865; Expressed in embryonic post-anal tail and 265 other tissues.
DR ExpressionAtlas; O70551; baseline and differential.
DR Genevisible; O70551; MM.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISO:MGI.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050684; P:regulation of mRNA processing; IDA:UniProtKB.
DR GO; GO:0000245; P:spliceosomal complex assembly; IBA:GO_Central.
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; Chromosome partition; Cytoplasm; Differentiation;
KW Direct protein sequencing; Endoplasmic reticulum; Kinase; Microsome;
KW mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..648
FT /note="SRSF protein kinase 1"
FT /id="PRO_0000086675"
FT DOMAIN 80..646
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..445
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 213
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 86..94
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UPE1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT MOD_RES 448
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 548
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT CONFLICT 113
FT /note="S -> I (in Ref. 2; CAA11833)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="G -> V (in Ref. 2; CAA11833)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="Q -> T (in Ref. 2; CAA11833)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="A -> P (in Ref. 1; BAA25299)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 648 AA; 73088 MW; CB779C163A11ECEB CRC64;
MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD IPEQEEEILG SDDDEQEDPN
DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI QGKKFVAMKV VKSAEHYTET
ALDEIRLLKS VRNSDPNDPN GEMVVQLLDD FKISGVNGTH ICMVFEVLGH HLLKWIIKSN
YQGLPLPCVK KIIQQVLQGL DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR
SGAPPPSGSA VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ
KRPNKQEESE SPVDRPLTEN PPNKMTQEKL EESNSIGQDQ TLTERGGEGG APEINCNGVI
GVVNYPENSN NETLRHKEDL HNANDCDVHT LKQEPSFLNS SNGDSSPSQD TDSCTPTASE
TMVCQSSAEQ SLTRQDITQL EESIRADTPS GDEQEPNGAL DSKGKFSAGN FLINPLEPKN
AEKLQVKIAD LGNACWVHKH FTEDIQTRQY RSLEVLIGSG YNTPADIWST ACMAFELATG
DYLFEPHSGE DYTRDEDHIA LIIELLGKVP RKLIVAGKYS KEFFTKKGDL KHITKLKPWG
LLEVLVEKYE WPQEEAAGFT DFLLPMLELM PEKRATAAEC LRHPWLNS
