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Protein

SRSF protein kinase 1

Gene

Srpk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/arginine-rich protein-specific kinase which specifically 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).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+2 Publications

Activity regulationi

Activated by phosphorylation on Ser-51 and Ser-548.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei109ATPPROSITE-ProRule annotationBy similarity1
Active sitei213Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 94ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processChromosome partition, Differentiation, mRNA processing, mRNA splicing
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
SRSF protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
SFRS protein kinase 1
Serine/arginine-rich protein-specific kinase 1
Short name:
SR-protein-specific kinase 1
Gene namesi
Name:Srpk1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:106908 Srpk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Microsome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866751 – 648SRSF protein kinase 1Add BLAST648

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51PhosphoserineCombined sources1
Modified residuei309PhosphoserineCombined sources1
Modified residuei311PhosphoserineCombined sources1
Modified residuei333PhosphoserineBy similarity1
Modified residuei448PhosphothreonineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei548Phosphoserine; by CK2By similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO70551
PaxDbiO70551
PeptideAtlasiO70551
PRIDEiO70551

PTM databases

iPTMnetiO70551
PhosphoSitePlusiO70551

Expressioni

Tissue specificityi

Predominantly expressed in the testis but is also present at lower levels in heart, spleen, liver, brain, kidney, lung and skeletal muscle. Present in all germinal cells in the seminiferous tubules but not in mature spermatozoa.2 Publications

Gene expression databases

BgeeiENSMUSG00000004865 Expressed in 309 organ(s), highest expression level in ear
CleanExiMM_SRPK1
ExpressionAtlasiO70551 baseline and differential
GenevisibleiO70551 MM

Interactioni

Subunit structurei

Monomer. Found in a multisubunit complex containing seven proteins, named toposome, which separates entangled circular chromatin DNA during chromosome segregation. Interacts with HHV-1 ICP27 protein. Interacts with DNAJC8 and AHSA1/AHA1 and this mediates formation of a complex with the Hsp70 /Hsp90 machinery. Binds to IGF2BP1, SYNCRIP, HNRNPA2B1 and HNRNPC. Interacts with SAFB/SAFB1 and SAFB2 which inhibits its activity (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SRSF1Q079555EBI-593343,EBI-398920From Homo sapiens.

Protein-protein interaction databases

IntActiO70551, 3 interactors
MINTiO70551
STRINGi10090.ENSMUSP00000116259

Structurei

3D structure databases

ProteinModelPortaliO70551
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 646Protein kinasePROSITE-ProRule annotationAdd BLAST567

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOGENOMiHOG000171558
HOVERGENiHBG108512
InParanoidiO70551
KOiK15409
OMAiEKYEWSK
OrthoDBiEOG091G05H9
PhylomeDBiO70551
TreeFamiTF105334

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O70551-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD IPEQEEEILG
60 70 80 90 100
SDDDEQEDPN DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI
110 120 130 140 150
QGKKFVAMKV VKSAEHYTET ALDEIRLLKS VRNSDPNDPN GEMVVQLLDD
160 170 180 190 200
FKISGVNGTH ICMVFEVLGH HLLKWIIKSN YQGLPLPCVK KIIQQVLQGL
210 220 230 240 250
DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR SGAPPPSGSA
260 270 280 290 300
VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ
310 320 330 340 350
KRPNKQEESE SPVDRPLTEN PPNKMTQEKL EESNSIGQDQ TLTERGGEGG
360 370 380 390 400
APEINCNGVI GVVNYPENSN NETLRHKEDL HNANDCDVHT LKQEPSFLNS
410 420 430 440 450
SNGDSSPSQD TDSCTPTASE TMVCQSSAEQ SLTRQDITQL EESIRADTPS
460 470 480 490 500
GDEQEPNGAL DSKGKFSAGN FLINPLEPKN AEKLQVKIAD LGNACWVHKH
510 520 530 540 550
FTEDIQTRQY RSLEVLIGSG YNTPADIWST ACMAFELATG DYLFEPHSGE
560 570 580 590 600
DYTRDEDHIA LIIELLGKVP RKLIVAGKYS KEFFTKKGDL KHITKLKPWG
610 620 630 640
LLEVLVEKYE WPQEEAAGFT DFLLPMLELM PEKRATAAEC LRHPWLNS
Length:648
Mass (Da):73,088
Last modified:June 21, 2005 - v2
Checksum:iCB779C163A11ECEB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WGJ7F8WGJ7_MOUSE
SRSF protein kinase 1
Srpk1
215Annotation score:
B2KF32B2KF32_MOUSE
SRSF protein kinase 1
Srpk1
35Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti113S → I in CAA11833 (PubMed:10390541).Curated1
Sequence conflicti155G → V in CAA11833 (PubMed:10390541).Curated1
Sequence conflicti256Q → T in CAA11833 (PubMed:10390541).Curated1
Sequence conflicti279A → P in BAA25299 (PubMed:9446799).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB012290 mRNA Translation: BAA25299.1
AJ224115 mRNA Translation: CAA11833.1
BC005707 mRNA Translation: AAH05707.1
BC050761 mRNA Translation: AAH50761.1
CCDSiCCDS37531.1
PIRiJC5930
RefSeqiNP_058075.2, NM_016795.4
UniGeneiMm.15252
Mm.479188

Genome annotation databases

EnsembliENSMUST00000130643; ENSMUSP00000116259; ENSMUSG00000004865
GeneIDi20815
KEGGimmu:20815
UCSCiuc008bri.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB012290 mRNA Translation: BAA25299.1
AJ224115 mRNA Translation: CAA11833.1
BC005707 mRNA Translation: AAH05707.1
BC050761 mRNA Translation: AAH50761.1
CCDSiCCDS37531.1
PIRiJC5930
RefSeqiNP_058075.2, NM_016795.4
UniGeneiMm.15252
Mm.479188

3D structure databases

ProteinModelPortaliO70551
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO70551, 3 interactors
MINTiO70551
STRINGi10090.ENSMUSP00000116259

PTM databases

iPTMnetiO70551
PhosphoSitePlusiO70551

Proteomic databases

EPDiO70551
PaxDbiO70551
PeptideAtlasiO70551
PRIDEiO70551

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000130643; ENSMUSP00000116259; ENSMUSG00000004865
GeneIDi20815
KEGGimmu:20815
UCSCiuc008bri.1 mouse

Organism-specific databases

CTDi6732
MGIiMGI:106908 Srpk1

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOGENOMiHOG000171558
HOVERGENiHBG108512
InParanoidiO70551
KOiK15409
OMAiEKYEWSK
OrthoDBiEOG091G05H9
PhylomeDBiO70551
TreeFamiTF105334

Miscellaneous databases

PROiPR:O70551
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004865 Expressed in 309 organ(s), highest expression level in ear
CleanExiMM_SRPK1
ExpressionAtlasiO70551 baseline and differential
GenevisibleiO70551 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRPK1_MOUSE
AccessioniPrimary (citable) accession number: O70551
Secondary accession number(s): O70193, Q99JT3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: June 21, 2005
Last modified: September 12, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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