EKS-MUM-00183

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00183

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CMGC/SRPK	854.1	8.7E-257	80	646	567

Status

Reviewed

Ensembl Protein

ENSMUSP00000116259

UniProt Accession

O70551; O70193; Q99JT3;

Protein Name

SRSF protein kinase 1

Protein Synonyms/Alias

SFRS protein kinase 1; Serine/arginine-rich protein-specific kinase 1; SR-protein-specific kinase 1;

Gene Name

Srpk1

Gene Synonyms/Alias

Srpk1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000004865	ENSMUSP00000116259	ENSMUST00000130643
ENSMUSG00000004865	ENSMUSP00000110415	ENSMUST00000114767
ENSMUSG00000004865	ENSMUSP00000004987	ENSMUST00000004987

Organism

Mus musculus

Functional Description

Serine/arginine-rich protein-specific kinase whichspecifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Phosphorylates SFRS2, ZRSR2, LBR and PRM1. Phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1- 8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Can induce splicing of exon 10 in MAPT/TAU (By similarity).

Protein Length

648

Protein Sequence
(FASTA)

MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD IPEQEEEILG SDDDEQEDPN 60

DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI QGKKFVAMKV VKSAEHYTET 120

ALDEIRLLKS VRNSDPNDPN GEMVVQLLDD FKISGVNGTH ICMVFEVLGH HLLKWIIKSN 180

YQGLPLPCVK KIIQQVLQGL DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR 240

SGAPPPSGSA VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ 300

KRPNKQEESE SPVDRPLTEN PPNKMTQEKL EESNSIGQDQ TLTERGGEGG APEINCNGVI 360

GVVNYPENSN NETLRHKEDL HNANDCDVHT LKQEPSFLNS SNGDSSPSQD TDSCTPTASE 420

TMVCQSSAEQ SLTRQDITQL EESIRADTPS GDEQEPNGAL DSKGKFSAGN FLINPLEPKN 480

AEKLQVKIAD LGNACWVHKH FTEDIQTRQY RSLEVLIGSG YNTPADIWST ACMAFELATG 540

DYLFEPHSGE DYTRDEDHIA LIIELLGKVP RKLIVAGKYS KEFFTKKGDL KHITKLKPWG 600

LLEVLVEKYE WPQEEAAGFT DFLLPMLELM PEKRATAAEC LRHPWLNS 648

Nucleotide Sequence
(FASTA)

ATGGAGCGGA AAGTGCTCGC GCTCCAGGCC CGAAAGAAAA GGACCAAGGC CAAGAAGGAC 60

AAAGCCCAAA GGAAGCCTGA AACTCAGCAC CGAGGCTCTG CACCCCACTC CGAGAGCGAC 120

ATCCCAGAGC AGGAGGAGGA GATTCTAGGG TCTGACGATG ACGAGCAGGA AGACCCCAAT 180

GACTACTGTA AAGGAGGTTA TCATCTTGTG AAAATTGGAG ATCTATTTAA CGGGAGATAC 240

CATGTGATTC GAAAATTGGG CTGGGGACAC TTTTCCACAG TGTGGTTATC ATGGGATATT 300

CAGGGAAAGA AGTTTGTAGC AATGAAAGTA GTTAAAAGTG CTGAGCATTA CACAGAAACA 360

GCACTAGATG AAATCCGGCT GCTGAAATCG GTTCGCAACT CAGACCCGAA TGATCCAAAT 420

GGAGAAATGG TTGTTCAACT ACTAGATGAC TTTAAAATAT CAGGCGTTAA TGGAACACAT 480

ATCTGCATGG TGTTTGAGGT TTTGGGGCAT CATCTACTCA AGTGGATCAT CAAGTCCAAC 540

TATCAGGGGC TTCCGCTGCC TTGTGTCAAA AAAATTATTC AGCAAGTGCT ACAGGGCCTG 600

GATTACTTAC ACACCAAGTG CCGGATCATC CACACGGACA TCAAACCAGA GAACATCTTG 660

TTGTCTGTGA ATGAGCAGTA CATTCGAAGG CTGGCTGCAG AGGCCACAGA GTGGCAGCGC 720

TCAGGAGCTC CCCCACCATC GGGGTCTGCA GTCAGCACTG CTCCACAGCC TAAGCCAGCT 780

GACAAAATGT CAAAGAATAA GAAGAAGAAA TTGAAGAAGA AGCAGAAGCG CCAGGCAGAA 840

TTACTAGAGA AGCGAATGCA GGAAATTGAG GAAATGGAGA AAGAGTCGGG CCCTGGGCAA 900

AAAAGACCTA ACAAGCAAGA AGAATCAGAG AGTCCTGTTG ACAGACCCCT GACAGAGAAC 960

CCACCTAATA AAATGACCCA AGAGAAACTT GAAGAGTCAA ATTCCATTGG CCAGGACCAG 1020

ACACTCACGG AGCGTGGTGG AGAGGGTGGT GCGCCAGAGA TTAATTGCAA TGGAGTGATT 1080

GGAGTCGTTA ATTACCCTGA GAACAGTAAT AATGAGACAC TGAGGCATAA AGAGGATCTG 1140

CATAATGCTA ATGACTGTGA TGTCCACACT TTGAAGCAGG AACCTAGTTT CCTAAACTCT 1200

TCAAATGGAG ACAGCAGTCC ATCTCAAGAC ACAGACTCTT GCACACCCAC GGCCTCTGAG 1260

ACCATGGTGT GCCAATCCTC TGCAGAGCAG TCACTCACCC GACAGGACAT CACCCAGCTG 1320

GAGGAGAGCA TTCGGGCAGA TACACCTTCT GGGGATGAGC AGGAGCCCAA TGGAGCCCTG 1380

GACAGCAAAG GAAAATTCTC TGCTGGAAAT TTTCTTATTA ATCCCCTTGA GCCAAAAAAT 1440

GCAGAGAAGC TCCAAGTGAA GATCGCAGAC CTCGGGAACG CCTGCTGGGT GCACAAGCAT 1500

TTCACTGAAG ATATCCAGAC ACGGCAGTAT CGGTCTTTGG AAGTCCTGAT AGGATCTGGC 1560

TACAACACCC CTGCTGACAT CTGGAGCACA GCATGCATGG CCTTTGAACT AGCCACAGGG 1620

GACTATTTGT TTGAGCCTCA TTCAGGGGAG GATTACACAC GAGATGAAGA CCACATCGCC 1680

CTGATCATAG AACTTCTGGG GAAGGTGCCT CGCAAGCTCA TTGTGGCAGG AAAATACTCC 1740

AAGGAATTTT TCACCAAAAA AGGTGACCTG AAGCACATCA CCAAGTTGAA GCCTTGGGGT 1800

CTTCTGGAGG TTCTGGTGGA GAAATATGAG TGGCCTCAGG AGGAGGCTGC CGGCTTCACA 1860

GATTTCCTGC TGCCCATGTT GGAGCTTATG CCTGAGAAGA GAGCCACTGC TGCTGAGTGT 1920

CTCCGGCATC CTTGGCTAAA CTCCTAA 1947

Domain Profile

S: 1     yhvirkLGWGhfstvWLawdlqekrfvalkvvksaehytetaldeikllksvresdpsdp  60

         yhvirkLGWGhfstvWL+wd+q+k+fva+kvvksaehytetaldei+llksvr+sdp+dp

Q: 80    YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDP  139

         9***********************************************************

S: 61    krekvvqllddfkisGvnGvhvclvfevLGenLlkliiksnyrGlpleqvkkiirqvLeg  120

         + e+vvqllddfkisGvnG+h+c+vfevLG++Llk+iiksny+Glpl++vkkii+qvL+g

Q: 140   NGEMVVQLLDDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQG  199

         ************************************************************

S: 121   LdylhekCkiihtdikPenvLlavddeyirrlaaeatewqkagakppsgsavstapqkka  180

         Ldylh+kC+iihtdikPen+Ll+v+++yirrlaaeatewq++ga+ppsgsavstapq+k+

Q: 200   LDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQRSGAPPPSGSAVSTAPQPKP  259

         ************************************************************

S: 181   ieklsknkkkklkkkqkrqaellekrlqeleele..........................  214

         ++k+sknkkkklkkkqkrqaellekr+qe+ee+e

Q: 260   ADKMSKNKKKKLKKKQKRQAELLEKRMQEIEEMEkesgpgqkrpnkqeesespvdrplte  319

         ************************************************************

S: 215   ..........aaeanseaedqelkedaekgeleeieadveeevanedeaseeee......  258

                   ++e+ns+ +dq+l+e+ ++g++ ei+++ ++ v+n+ e+s++e+

Q: 320   nppnkmtqekLEESNSIGQDQTLTERGGEGGAPEINCNGVIGVVNYPENSNNETlrhked  379

         *********999****************************************99******

S: 259   ..............essltsssdaesksgelseastellsesleqlacgsvls.......  297

                       e s+++ss+ +s+ +++++++t+++se   +++c+s+++

Q: 380   lhnandcdvhtlkqEPSFLNSSNGDSSPSQDTDSCTPTASE---TMVCQSSAEqsltrqd  436

         *************************************9998...67888887778889**

S: 298   ....................................vnplepknadkikvkiadLGnaCw  321

                                             +nplepkna+k++vkiadLGnaCw

Q: 437   itqleesiradtpsgdeqepngaldskgkfsagnflINPLEPKNAEKLQVKIADLGNACW  496

         ************************************************************

S: 322   vhkhftediqtrqyrslevliGagygtpadiWstaClafeLatGdyLfephsgedysrde  381

         vhkhftediqtrqyrslevliG+gy+tpadiWstaC+afeLatGdyLfephsgedy+rde

Q: 497   VHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSGEDYTRDE  556

         ************************************************************

S: 382   dhiakiiellGkiPrklilkGkysreffnkkgeLrhitkLkpwsLlevLvekyewskeea  441

         dhia iiellGk+Prkli++Gkys+eff+kkg+L+hitkLkpw+LlevLvekyew++eea

Q: 557   DHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLLEVLVEKYEWPQEEA  616

         ************************************************************

S: 442   aefsdfLlPmleldpekrasaaeclkhpwL  471

         a f+dfLlPmlel+pekra+aaecl+hpwL

Q: 617   AGFTDFLLPMLELMPEKRATAAECLRHPWL  646

         *****************************8

Domain Sequence
(FASTA)

YHVIRKLGWG HFSTVWLSWD IQGKKFVAMK VVKSAEHYTE TALDEIRLLK SVRNSDPNDP 60

NGEMVVQLLD DFKISGVNGT HICMVFEVLG HHLLKWIIKS NYQGLPLPCV KKIIQQVLQG 120

LDYLHTKCRI IHTDIKPENI LLSVNEQYIR RLAAEATEWQ RSGAPPPSGS AVSTAPQPKP 180

ADKMSKNKKK KLKKKQKRQA ELLEKRMQEI EEMEKESGPG QKRPNKQEES ESPVDRPLTE 240

NPPNKMTQEK LEESNSIGQD QTLTERGGEG GAPEINCNGV IGVVNYPENS NNETLRHKED 300

LHNANDCDVH TLKQEPSFLN SSNGDSSPSQ DTDSCTPTAS ETMVCQSSAE QSLTRQDITQ 360

LEESIRADTP SGDEQEPNGA LDSKGKFSAG NFLINPLEPK NAEKLQVKIA DLGNACWVHK 420

HFTEDIQTRQ YRSLEVLIGS GYNTPADIWS TACMAFELAT GDYLFEPHSG EDYTRDEDHI 480

ALIIELLGKV PRKLIVAGKY SKEFFTKKGD LKHITKLKPW GLLEVLVEKY EWPQEEAAGF 540

TDFLLPMLEL MPEKRATAAE CLRHPWL 567

Keyword

Acetylation; ATP-binding; Chromosome partition; Complete proteome; Cytoplasm; Differentiation; Direct protein sequencing; Endoplasmic reticulum; Kinase; Microsome; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Choloepus hoffmanni"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005783	; C:endoplasmic reticulum
GO:0016363	; C:nuclear matrix
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0030154	; P:cell differentiation
GO:0007059	; P:chromosome segregation
GO:0007243	; P:intracellular protein kinase cascade
GO:0006397	; P:mRNA processing
GO:0045071	; P:negative regulation of viral genome replication
GO:0045070	; P:positive regulation of viral genome replication
GO:0050684	; P:regulation of mRNA processing
GO:0008380	; P:RNA splicing

KEGG

mmu:20815

;

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00069

; Pkinase; 2.

SMARTs

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013