O70551 (SRPK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 125. History...
Names and origin
|Protein names||Recommended name:|
SRSF protein kinase 1
SFRS protein kinase 1
Serine/arginine-rich protein-specific kinase 1
Short name=SR-protein-specific kinase 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||648 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
Activated by phosphorylation on Ser-51 and Ser-548 By similarity. UniProtKB Q96SB4
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.
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
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
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 648||648||SRSF protein kinase 1||PRO_0000086675|
|Domain||80 – 646||567||Protein kinase|
|Nucleotide binding||86 – 94||9||ATP By similarity UniProtKB Q9UPE1|
|Active site||213||1||Proton acceptor By similarity UniProtKB Q9UPE1|
|Binding site||109||1||ATP By similarity UniProtKB Q9UPE1|
Amino acid modifications
|Modified residue||51||1||Phosphoserine Ref.6 UniProtKB Q96SB4|
|Modified residue||309||1||Phosphoserine Ref.6|
|Modified residue||311||1||Phosphoserine Ref.6|
|Modified residue||448||1||Phosphothreonine Ref.6|
|Modified residue||450||1||Phosphoserine Ref.6|
|Modified residue||548||1||Phosphoserine; by CK2 By similarity UniProtKB Q96SB4|
|Sequence conflict||113||1||S → I in CAA11833. Ref.2|
|Sequence conflict||155||1||G → V in CAA11833. Ref.2|
|Sequence conflict||256||1||Q → T in CAA11833. Ref.2|
|Sequence conflict||279||1||A → P in BAA25299. Ref.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.
|||"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.
|||"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].
Tissue: Mammary gland and Testis.
|||Lubec G., Sunyer B., Chen W.-Q.|
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 573-581, IDENTIFICATION BY MASS SPECTROMETRY.
|||"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.
|||"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].
|+||Additional computationally mapped references.|
|AB012290 mRNA. Translation: BAA25299.1.|
AJ224115 mRNA. Translation: CAA11833.1.
BC005707 mRNA. Translation: AAH05707.1.
BC050761 mRNA. Translation: AAH50761.1.
|RefSeq||NP_058075.2. NM_016795.3. |
3D structure databases
|SMR||O70551. Positions 63-263, 467-648. |
Protein-protein interaction databases
|IntAct||O70551. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000130643; ENSMUSP00000116259; ENSMUSG00000004865. |
|UCSC||uc008bri.1. mouse. |
|MGI||MGI:106908. Srpk1. |
Gene expression databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 2 hits. |
|SUPFAM||SSF56112. SSF56112. 2 hits. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: O70551|
Secondary accession number(s): O70193, Q99JT3
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|