SRPK1_PONAB
ID SRPK1_PONAB Reviewed; 655 AA.
AC Q5RD27;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 106.
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:0000250|UniProtKB:Q96SB4};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1] {ECO:0000312|EMBL:CAH90330.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex {ECO:0000312|EMBL:CAH90330.1};
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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.
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:0000250|UniProtKB:Q96SB4};
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:0000250|UniProtKB:Q96SB4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96SB4};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Ser-51 and Ser-
CC 555. {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 -!- 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. Inhibition of the Hsp90 ATPase activity, osmotic stress
CC and interaction with HHV-1 ICP27 protein can induce its translocation
CC to the nucleus. KAT5/TIP60 inhibits its nuclear translocation.
CC Preferentially localizes to the promoter of gene coding regions.
CC {ECO:0000250|UniProtKB:Q96SB4}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH90330.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; CR858091; CAH90330.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001125155.1; NM_001131683.1.
DR AlphaFoldDB; Q5RD27; -.
DR SMR; Q5RD27; -.
DR STRING; 9601.ENSPPYP00000018496; -.
DR GeneID; 100172042; -.
DR KEGG; pon:100172042; -.
DR CTD; 6732; -.
DR eggNOG; KOG1290; Eukaryota.
DR InParanoid; Q5RD27; -.
DR OrthoDB; 290680at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050684; P:regulation of mRNA processing; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW ATP-binding; Chromosome; Chromosome partition; Cytoplasm; Differentiation;
KW Endoplasmic reticulum; Kinase; Microsome; mRNA processing; mRNA splicing;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..655
FT /note="SRSF protein kinase 1"
FT /id="PRO_0000086676"
FT DOMAIN 80..653
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..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..417
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..326
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..341
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; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
FT MOD_RES 555
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q96SB4"
SQ SEQUENCE 655 AA; 74407 MW; 9F74B87430FF0F80 CRC64;
MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD LPEQEEEILG SDDDEQEDPN
DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI QGKKFVAMKV VKSAEHYTET
ALDEIRLLKS VRNSDPNDPN REMVVQLLDD FKISGVNGTH ICMVFEVLGH HLLKWIIKSN
YQGLPLPCVK KIIQQVLQGL DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR
SGAPPPSGSA VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ
KRPNKQEESE SPVERPLKEN PPNKMTQEKL EESSTIGQDQ TLMERDTEGG AAEINCNGVV
EVINYTQNSN NETLRHKEDL HNANDCDVQN LNQESSFLSS QNGDSSTSQE TDSCTPITSE
VSDTMVCQSS STVDQSFSEQ HISQLQESIR VEIPCEDEQE QEHNGPLDNK GKSTAGNFLV
NPLEPKNAEK LKVKIADLGN ACWVHKHFTE DIQTRQYRSL EVLIGSGYNT PADIWSTACM
AFELATGDYL FEPHSGEEYT RDEDHIALII ELLGKVPRKL IVAGKYSKEF FTKKGDLKHI
TKLKPWGLFE VLVEKYEWSQ EEAAGFTDFL LPMLELIPEK RATAAECLRH PWLNS
