EKS-HOS-00184

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00184

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CMGC/SRPK	867.7	1.3E-260	64	637	574

Status

Reviewed

Ensembl Protein

ENSP00000391069

UniProt Accession

Q96SB4; Q12890; Q5R364; Q5R365; Q8IY12;

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
ENSG00000096063	ENSP00000362928	ENST00000373822
ENSG00000096063	ENSP00000425172	ENST00000508473
ENSG00000096063	ENSP00000354674	ENST00000361690
ENSG00000096063	ENSP00000424170	ENST00000510290
ENSG00000096063	ENSP00000362931	ENST00000373825
ENSG00000096063	ENSP00000422886	ENST00000507292
ENSG00000096063	ENSP00000391069	ENST00000423325
ENSG00000096063	ENSP00000424323	ENST00000507909
ENSG00000096063	ENSP00000424068	ENST00000512445

Organism

Homo sapiens

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. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 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. Isoform 2 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. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.

Protein Length

639

Protein Sequence
(FASTA)

MGIFVSFLRS ETQHRGSAPH SESDLPEQEE EILGSDDDEQ EDPNDYCKGG YHLVKIGDLF 60

NGRYHVIRKL GWGHFSTVWL SWDIQGKKFV AMKVVKSAEH YTETALDEIR LLKSVRNSDP 120

NDPNREMVVQ LLDDFKISGV NGTHICMVFE VLGHHLLKWI IKSNYQGLPL PCVKKIIQQV 180

LQGLDYLHTK CRIIHTDIKP ENILLSVNEQ YIRRLAAEAT EWQRSGAPPP SGSAVSTAPQ 240

PKPADKMSKN KKKKLKKKQK RQAELLEKRM QEIEEMEKES GPGQKRPNKQ EESESPVERP 300

LKENPPNKMT QEKLEESSTI GQDQTLMERD TEGGAAEINC NGVIEVINYT QNSNNETLRH 360

KEDLHNANDC DVQNLNQESS FLSSQNGDSS TSQETDSCTP ITSEVSDTMV CQSSSTVGQS 420

FSEQHISQLQ ESIRAEIPCE DEQEQEHNGP LDNKGKSTAG NFLVNPLEPK NAEKLKVKIA 480

DLGNACWVHK HFTEDIQTRQ YRSLEVLIGS GYNTPADIWS TACMAFELAT GDYLFEPHSG 540

EEYTRDEDHI ALIIELLGKV PRKLIVAGKY SKEFFTKKGD LKHITKLKPW GLFEVLVEKY 600

EWSQEEAAGF TDFLLPMLEL IPEKRATAAE CLRHPWLNS 639

Nucleotide Sequence
(FASTA)

ATGGGCATTT TTGTATCATT TCTTAGATCT GAAACTCAGC ACCGAGGCTC TGCTCCCCAC 60

TCTGAGAGTG ATCTACCAGA GCAGGAAGAG GAGATTCTGG GATCTGATGA TGATGAGCAA 120

GAAGATCCTA ATGATTATTG TAAAGGAGGT TATCATCTTG TGAAAATTGG AGATCTATTC 180

AATGGGAGAT ACCATGTGAT CCGAAAGTTA GGCTGGGGAC ACTTTTCAAC AGTATGGTTA 240

TCATGGGATA TTCAGGGGAA GAAATTTGTG GCAATGAAAG TAGTTAAAAG TGCTGAACAT 300

TACACTGAAA CAGCACTAGA TGAAATCCGG TTGCTGAAGT CAGTTCGCAA TTCAGACCCT 360

AATGATCCAA ATAGAGAAAT GGTTGTTCAA CTACTAGATG ACTTTAAAAT ATCAGGAGTT 420

AATGGAACAC ATATCTGCAT GGTATTTGAA GTTTTGGGGC ATCATCTGCT CAAGTGGATC 480

ATCAAATCCA ATTATCAGGG GCTTCCACTG CCTTGTGTCA AAAAAATTAT TCAGCAAGTG 540

TTACAGGGTC TTGATTATTT ACATACCAAG TGCCGTATCA TCCACACTGA CATTAAACCA 600

GAGAACATCT TATTGTCAGT GAATGAGCAG TACATTCGGA GGCTGGCTGC AGAAGCAACA 660

GAATGGCAGC GATCTGGAGC TCCTCCGCCT TCCGGATCTG CAGTCAGTAC TGCTCCCCAG 720

CCTAAACCAG CTGACAAAAT GTCAAAGAAT AAGAAGAAGA AATTGAAGAA GAAGCAGAAG 780

CGCCAGGCAG AATTACTAGA GAAGCGAATG CAGGAAATTG AGGAAATGGA GAAAGAGTCG 840

GGCCCTGGGC AAAAAAGACC AAACAAGCAA GAAGAATCAG AGAGTCCTGT TGAAAGACCC 900

TTGAAAGAGA ACCCACCTAA TAAAATGACC CAAGAAAAAC TTGAAGAGTC AAGTACCATT 960

GGCCAGGATC AAACGCTTAT GGAACGTGAT ACAGAGGGTG GTGCAGCAGA AATTAATTGC 1020

AATGGAGTGA TTGAAGTCAT TAATTATACT CAGAACAGTA ATAATGAAAC ATTGAGACAT 1080

AAAGAGGATC TACATAATGC TAATGACTGT GATGTCCAAA ATTTGAATCA GGAATCTAGT 1140

TTCCTAAGCT CCCAAAATGG AGACAGCAGC ACATCTCAAG AAACAGACTC TTGTACACCT 1200

ATAACATCTG AGGTGTCAGA CACCATGGTG TGCCAGTCTT CCTCAACTGT AGGTCAGTCA 1260

TTCAGTGAAC AACACATTAG CCAACTTCAA GAAAGCATTC GGGCAGAGAT ACCCTGTGAA 1320

GATGAACAAG AGCAAGAACA TAACGGACCA CTGGACAACA AAGGAAAATC CACGGCTGGA 1380

AATTTTCTTG TTAATCCCCT TGAGCCAAAA AATGCAGAAA AGCTCAAGGT GAAGATTGCT 1440

GACCTTGGAA ATGCTTGTTG GGTGCACAAA CATTTCACTG AAGATATTCA AACAAGGCAA 1500

TATCGTTCCT TGGAAGTTCT AATCGGATCT GGCTATAATA CCCCTGCTGA CATTTGGAGC 1560

ACGGCATGCA TGGCCTTTGA ACTGGCCACA GGTGACTATT TGTTTGAACC TCATTCAGGG 1620

GAAGAGTACA CTCGAGATGA AGATCACATT GCATTGATCA TAGAACTTCT GGGGAAGGTG 1680

CCTCGCAAGC TCATTGTGGC AGGAAAATAT TCCAAGGAAT TTTTCACCAA AAAAGGTGAC 1740

CTGAAACATA TCACGAAGCT GAAACCTTGG GGCCTTTTTG AGGTTCTAGT GGAGAAGTAT 1800

GAGTGGTCGC AGGAAGAGGC AGCTGGCTTC ACAGATTTCT TACTGCCCAT GTTGGAGCTG 1860

ATCCCTGAGA AGAGAGCCAC TGCCGCCGAG TGTCTCCGGC ACCCTTGGCT TAACTCCTAA 1920

Domain Profile

S: 1     yhvirkLGWGhfstvWLawdlqekrfvalkvvksaehytetaldeikllksvresdpsdp  60

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

Q: 64    YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDP  123

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

S: 61    krekvvqllddfkisGvnGvhvclvfevLGenLlkliiksnyrGlpleqvkkiirqvLeg  120

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

Q: 124   NREMVVQLLDDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQG  183

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

S: 121   LdylhekCkiihtdikPenvLlavddeyirrlaaeatewqkagakppsgsavstapqkka  180

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

Q: 184   LDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQRSGAPPPSGSAVSTAPQPKP  243

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

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

         ++k+sknkkkklkkkqkrqaellekr+qe+ee+e

Q: 244   ADKMSKNKKKKLKKKQKRQAELLEKRMQEIEEMEkesgpgqkrpnkqeesespverplke  303

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

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

                   ++e++++ +dq+l+e++++g+++ei+++ ++ev+n++++s++e+

Q: 304   nppnkmtqekLEESSTIGQDQTLMERDTEGGAAEINCNGVIEVINYTQNSNNETlrhked  363

         *********9999************************************9999999****

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

                       ess++ss++ +s+++++++++t+++se++++++c+s+++

Q: 364   lhnandcdvqnlnqESSFLSSQNGDSSTSQETDSCTPITSEVSDTMVCQSSSTvgqsfse  423

         *************9*************************************999******

S: 298   ........................................vnplepknadkikvkiadLG  317

                                                 vnplepkna+k+kvkiadLG

Q: 424   qhisqlqesiraeipcedeqeqehngpldnkgkstagnflVNPLEPKNAEKLKVKIADLG  483

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

S: 318   naCwvhkhftediqtrqyrslevliGagygtpadiWstaClafeLatGdyLfephsgedy  377

         naCwvhkhftediqtrqyrslevliG+gy+tpadiWstaC+afeLatGdyLfephsge+y

Q: 484   NACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSGEEY  543

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

S: 378   srdedhiakiiellGkiPrklilkGkysreffnkkgeLrhitkLkpwsLlevLvekyews  437

         +rdedhia iiellGk+Prkli++Gkys+eff+kkg+L+hitkLkpw+L+evLvekyews

Q: 544   TRDEDHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWS  603

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

S: 438   keeaaefsdfLlPmleldpekrasaaeclkhpwL  471

         +eeaa f+dfLlPmlel+pekra+aaecl+hpwL

Q: 604   QEEAAGFTDFLLPMLELIPEKRATAAECLRHPWL  637

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

Domain Sequence
(FASTA)

YHVIRKLGWG HFSTVWLSWD IQGKKFVAMK VVKSAEHYTE TALDEIRLLK SVRNSDPNDP 60

NREMVVQLLD DFKISGVNGT HICMVFEVLG HHLLKWIIKS NYQGLPLPCV KKIIQQVLQG 120

LDYLHTKCRI IHTDIKPENI LLSVNEQYIR RLAAEATEWQ RSGAPPPSGS AVSTAPQPKP 180

ADKMSKNKKK KLKKKQKRQA ELLEKRMQEI EEMEKESGPG QKRPNKQEES ESPVERPLKE 240

NPPNKMTQEK LEESSTIGQD QTLMERDTEG GAAEINCNGV IEVINYTQNS NNETLRHKED 300

LHNANDCDVQ NLNQESSFLS SQNGDSSTSQ ETDSCTPITS EVSDTMVCQS SSTVGQSFSE 360

QHISQLQESI RAEIPCEDEQ EQEHNGPLDN KGKSTAGNFL VNPLEPKNAE KLKVKIADLG 420

NACWVHKHFT EDIQTRQYRS LEVLIGSGYN TPADIWSTAC MAFELATGDY LFEPHSGEEY 480

TRDEDHIALI IELLGKVPRK LIVAGKYSKE FFTKKGDLKH ITKLKPWGLF EVLVEKYEWS 540

QEEAAGFTDF LLPMLELIPE KRATAAECLR HPWL 574

Keyword

3D-structure; Acetylation; Alternative splicing; ATP-binding; Chromosome partition; Complete proteome; Cytoplasm; Differentiation; Direct protein sequencing; Endoplasmic reticulum; Host-virus interaction; Kinase; Microsome; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; 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"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>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:0007059	; P:chromosome segregation
GO:0045087	; P:innate immune response
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:0048024	; P:regulation of mRNA splicing, via spliceosome
GO:0008380	; P:RNA splicing
GO:0035092	; P:sperm chromatin condensation
GO:0019048	; P:virus-host interaction

KEGG

hsa:6732

;

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