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O70551 (SRPK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Srpk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length648 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2

Cofactor

Magnesium. Ref.1 Ref.2

Enzyme regulation

Activated by phosphorylation on Ser-51 and Ser-548 By similarity. UniProtKB Q96SB4

Subunit structure

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 DNAJB1/HSP40 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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Nucleus matrix By similarity. Microsome By similarity. Note: Shuttles between the nucleus and the cytoplasm. Inhibition of the Hsp90 ATPase activity, osmotic stress and interaction with HHV-1 ICP27 protein can induce its translocation to the nucleus. KAT5/TIP60 inhibits its nuclear translocation By similarity. Ref.1

Tissue specificity

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. Ref.1 Ref.2

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processChromosome partition
Differentiation
mRNA processing
mRNA splicing
   Cellular componentCytoplasm
Endoplasmic reticulum
Microsome
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

chromosome segregation

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

mRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of viral genome replication

Inferred from electronic annotation. Source: Ensembl

positive regulation of viral genome replication

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of mRNA processing

Inferred from direct assay Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10196197. Source: IntAct

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SRSF1Q079555EBI-593343,EBI-398920From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 648648SRSF protein kinase 1
PRO_0000086675

Regions

Domain80 – 646567Protein kinase
Nucleotide binding86 – 949ATP By similarity UniProtKB Q9UPE1

Sites

Active site2131Proton acceptor By similarity UniProtKB Q9UPE1
Binding site1091ATP By similarity UniProtKB Q9UPE1

Amino acid modifications

Modified residue511Phosphoserine Ref.6 UniProtKB Q96SB4
Modified residue3091Phosphoserine Ref.6
Modified residue3111Phosphoserine Ref.6
Modified residue4481Phosphothreonine Ref.6
Modified residue4501Phosphoserine Ref.6
Modified residue5481Phosphoserine; by CK2 By similarity UniProtKB Q96SB4

Experimental info

Sequence conflict1131S → I in CAA11833. Ref.2
Sequence conflict1551G → V in CAA11833. Ref.2
Sequence conflict2561Q → T in CAA11833. Ref.2
Sequence conflict2791A → P in BAA25299. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O70551 [UniParc].

Last modified June 21, 2005. Version 2.
Checksum: CB779C163A11ECEB

FASTA64873,088
        10         20         30         40         50         60 
MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD IPEQEEEILG SDDDEQEDPN 

        70         80         90        100        110        120 
DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI QGKKFVAMKV VKSAEHYTET 

       130        140        150        160        170        180 
ALDEIRLLKS VRNSDPNDPN GEMVVQLLDD FKISGVNGTH ICMVFEVLGH HLLKWIIKSN 

       190        200        210        220        230        240 
YQGLPLPCVK KIIQQVLQGL DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR 

       250        260        270        280        290        300 
SGAPPPSGSA VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ 

       310        320        330        340        350        360 
KRPNKQEESE SPVDRPLTEN PPNKMTQEKL EESNSIGQDQ TLTERGGEGG APEINCNGVI 

       370        380        390        400        410        420 
GVVNYPENSN NETLRHKEDL HNANDCDVHT LKQEPSFLNS SNGDSSPSQD TDSCTPTASE 

       430        440        450        460        470        480 
TMVCQSSAEQ SLTRQDITQL EESIRADTPS GDEQEPNGAL DSKGKFSAGN FLINPLEPKN 

       490        500        510        520        530        540 
AEKLQVKIAD LGNACWVHKH FTEDIQTRQY RSLEVLIGSG YNTPADIWST ACMAFELATG 

       550        560        570        580        590        600 
DYLFEPHSGE DYTRDEDHIA LIIELLGKVP RKLIVAGKYS KEFFTKKGDL KHITKLKPWG 

       610        620        630        640 
LLEVLVEKYE WPQEEAAGFT DFLLPMLELM PEKRATAAEC LRHPWLNS 

« Hide

References

« Hide 'large scale' references
[1]"Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles."
Kuroyanagi N., Onogi H., Wakabayashi T., Hagiwara M.
Biochem. Biophys. Res. Commun. 242:357-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1."
Papoutsopoulou S., Nikolakaki E., Chalepakis G., Kruft V., Chevaillier P., Giannakouros T.
Nucleic Acids Res. 27:2972-2980(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Embryo.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary gland and Testis.
[4]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 573-581, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[5]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-309; SER-311; THR-448 AND SER-450, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012290 mRNA. Translation: BAA25299.1.
AJ224115 mRNA. Translation: CAA11833.1.
BC005707 mRNA. Translation: AAH05707.1.
BC050761 mRNA. Translation: AAH50761.1.
CCDSCCDS37531.1.
PIRJC5930.
RefSeqNP_058075.2. NM_016795.3.
UniGeneMm.15252.
Mm.479188.

3D structure databases

ProteinModelPortalO70551.
SMRO70551. Positions 63-263, 467-648.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO70551. 2 interactions.
MINTMINT-4123549.

PTM databases

PhosphoSiteO70551.

Proteomic databases

MaxQBO70551.
PaxDbO70551.
PRIDEO70551.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000130643; ENSMUSP00000116259; ENSMUSG00000004865.
GeneID20815.
KEGGmmu:20815.
UCSCuc008bri.1. mouse.

Organism-specific databases

CTD6732.
MGIMGI:106908. Srpk1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000171558.
HOVERGENHBG108512.
InParanoidO70551.
KOK15409.
OMAQSFSEQH.
OrthoDBEOG70S74X.
PhylomeDBO70551.
TreeFamTF105334.

Gene expression databases

ArrayExpressO70551.
BgeeO70551.
CleanExMM_SRPK1.
GenevestigatorO70551.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 2 hits.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio299541.
PROO70551.
SOURCESearch...

Entry information

Entry nameSRPK1_MOUSE
AccessionPrimary (citable) accession number: O70551
Secondary accession number(s): O70193, Q99JT3
Entry history
Integrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: June 21, 2005
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot