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O70551

- SRPK1_MOUSE

UniProt

O70551 - SRPK1_MOUSE

Protein

SRSF protein kinase 1

Gene

Srpk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (21 Jun 2005)
      Previous versions | rss
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    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 similarity

    Catalytic activityi

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

    Cofactori

    Magnesium.2 Publications

    Enzyme regulationi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei109 – 1091ATPBy similarityPROSITE-ProRule annotation
    Active sitei213 – 2131Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi86 – 949ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. magnesium ion binding Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. chromosome segregation Source: UniProtKB
    3. intracellular signal transduction Source: UniProtKB
    4. mRNA processing Source: UniProtKB-KW
    5. negative regulation of viral genome replication Source: Ensembl
    6. positive regulation of viral genome replication Source: Ensembl
    7. protein phosphorylation Source: UniProtKB
    8. regulation of mRNA processing Source: UniProtKB
    9. RNA splicing Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Chromosome partition, Differentiation, mRNA processing, mRNA splicing

    Keywords - Ligandi

    ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:106908. Srpk1.

    Subcellular locationi

    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum Source: UniProtKB-KW
    3. nuclear matrix Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Microsome, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 648648SRSF protein kinase 1PRO_0000086675Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei51 – 511Phosphoserine1 Publication
    Modified residuei309 – 3091Phosphoserine1 Publication
    Modified residuei311 – 3111Phosphoserine1 Publication
    Modified residuei448 – 4481Phosphothreonine1 Publication
    Modified residuei450 – 4501Phosphoserine1 Publication
    Modified residuei548 – 5481Phosphoserine; by CK2By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO70551.
    PaxDbiO70551.
    PRIDEiO70551.

    PTM databases

    PhosphoSiteiO70551.

    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

    ArrayExpressiO70551.
    BgeeiO70551.
    CleanExiMM_SRPK1.
    GenevestigatoriO70551.

    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 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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SRSF1Q079555EBI-593343,EBI-398920From a different organism.

    Protein-protein interaction databases

    IntActiO70551. 2 interactions.
    MINTiMINT-4123549.

    Structurei

    3D structure databases

    ProteinModelPortaliO70551.
    SMRiO70551. Positions 63-263, 467-648.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini80 – 646567Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000171558.
    HOVERGENiHBG108512.
    InParanoidiO70551.
    KOiK15409.
    OMAiQSFSEQH.
    OrthoDBiEOG70S74X.
    PhylomeDBiO70551.
    TreeFamiTF105334.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 2 hits.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 2 hits.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O70551-1 [UniParc]FASTAAdd to Basket

    « Hide

    MERKVLALQA RKKRTKAKKD KAQRKPETQH RGSAPHSESD IPEQEEEILG    50
    SDDDEQEDPN DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI 100
    QGKKFVAMKV VKSAEHYTET ALDEIRLLKS VRNSDPNDPN GEMVVQLLDD 150
    FKISGVNGTH ICMVFEVLGH HLLKWIIKSN YQGLPLPCVK KIIQQVLQGL 200
    DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR SGAPPPSGSA 250
    VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ 300
    KRPNKQEESE SPVDRPLTEN PPNKMTQEKL EESNSIGQDQ TLTERGGEGG 350
    APEINCNGVI GVVNYPENSN NETLRHKEDL HNANDCDVHT LKQEPSFLNS 400
    SNGDSSPSQD TDSCTPTASE TMVCQSSAEQ SLTRQDITQL EESIRADTPS 450
    GDEQEPNGAL DSKGKFSAGN FLINPLEPKN AEKLQVKIAD LGNACWVHKH 500
    FTEDIQTRQY RSLEVLIGSG YNTPADIWST ACMAFELATG DYLFEPHSGE 550
    DYTRDEDHIA LIIELLGKVP RKLIVAGKYS KEFFTKKGDL KHITKLKPWG 600
    LLEVLVEKYE WPQEEAAGFT DFLLPMLELM PEKRATAAEC LRHPWLNS 648
    Length:648
    Mass (Da):73,088
    Last modified:June 21, 2005 - v2
    Checksum:iCB779C163A11ECEB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti113 – 1131S → I in CAA11833. (PubMed:10390541)Curated
    Sequence conflicti155 – 1551G → V in CAA11833. (PubMed:10390541)Curated
    Sequence conflicti256 – 2561Q → T in CAA11833. (PubMed:10390541)Curated
    Sequence conflicti279 – 2791A → P in BAA25299. (PubMed:9446799)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_016795.3.
    UniGeneiMm.15252.
    Mm.479188.

    Genome annotation databases

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

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB012290 mRNA. Translation: BAA25299.1 .
    AJ224115 mRNA. Translation: CAA11833.1 .
    BC005707 mRNA. Translation: AAH05707.1 .
    BC050761 mRNA. Translation: AAH50761.1 .
    CCDSi CCDS37531.1.
    PIRi JC5930.
    RefSeqi NP_058075.2. NM_016795.3.
    UniGenei Mm.15252.
    Mm.479188.

    3D structure databases

    ProteinModelPortali O70551.
    SMRi O70551. Positions 63-263, 467-648.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O70551. 2 interactions.
    MINTi MINT-4123549.

    PTM databases

    PhosphoSitei O70551.

    Proteomic databases

    MaxQBi O70551.
    PaxDbi O70551.
    PRIDEi O70551.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000130643 ; ENSMUSP00000116259 ; ENSMUSG00000004865 .
    GeneIDi 20815.
    KEGGi mmu:20815.
    UCSCi uc008bri.1. mouse.

    Organism-specific databases

    CTDi 6732.
    MGIi MGI:106908. Srpk1.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000171558.
    HOVERGENi HBG108512.
    InParanoidi O70551.
    KOi K15409.
    OMAi QSFSEQH.
    OrthoDBi EOG70S74X.
    PhylomeDBi O70551.
    TreeFami TF105334.

    Miscellaneous databases

    NextBioi 299541.
    PROi O70551.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O70551.
    Bgeei O70551.
    CleanExi MM_SRPK1.
    Genevestigatori O70551.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 2 hits.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: Brain1 Publication.
    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: EmbryoImported.
    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/NImported.
      Tissue: Mammary glandImported and TestisImported.
    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.
    6. 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.

    Entry informationi

    Entry nameiSRPK1_MOUSE
    AccessioniPrimary (citable) accession number: O70551
    Secondary accession number(s): O70193, Q99JT3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 21, 2005
    Last sequence update: June 21, 2005
    Last modified: October 1, 2014
    This is version 126 of the entry and version 2 of the sequence. [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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3