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Q8CFH6

- SIK2_MOUSE

UniProt

Q8CFH6 - SIK2_MOUSE

Protein

Serine/threonine-protein kinase SIK2

Gene

Sik2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Phosphorylates 'Ser-789' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.1 Publication

    Enzyme regulationi

    Activated by phosphorylation on Thr-175.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei49 – 491ATP1 PublicationPROSITE-ProRule annotation
    Active sitei142 – 1421Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi26 – 349ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. insulin receptor signaling pathway Source: MGI
    2. intracellular signal transduction Source: UniProtKB
    3. protein autophosphorylation Source: UniProtKB
    4. protein phosphorylation Source: UniProtKB
    5. regulation of insulin receptor signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase SIK2 (EC:2.7.11.1)
    Alternative name(s):
    Salt-inducible kinase 2
    Short name:
    SIK-2
    Serine/threonine-protein kinase SNF1-like kinase 2
    Gene namesi
    Name:Sik2
    Synonyms:Snf1lk2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:2445031. Sik2.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi49 – 491K → M: Loss of kinase activity. 2 Publications
    Mutagenesisi175 – 1751T → E: Low levels of constitutive activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 931931Serine/threonine-protein kinase SIK2PRO_0000086663Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei25 – 251PhosphothreonineBy similarity
    Modified residuei53 – 531N6-acetyllysine; by EP300By similarity
    Modified residuei175 – 1751PhosphothreonineBy similarity
    Modified residuei587 – 5871PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.By similarity
    Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ8CFH6.
    PaxDbiQ8CFH6.
    PRIDEiQ8CFH6.

    PTM databases

    PhosphoSiteiQ8CFH6.

    Expressioni

    Tissue specificityi

    Present in both white and brown adipose tissues with levels increasing during adipocyte differentiation. Lower levels observed in the testis.1 Publication

    Gene expression databases

    CleanExiMM_SNF1LK2.
    GenevestigatoriQ8CFH6.

    Interactioni

    Subunit structurei

    Interacts with and phosphorylates TORC2/CRTC2.By similarity

    Protein-protein interaction databases

    BioGridi231647. 1 interaction.
    DIPiDIP-60734N.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CFH6.
    SMRiQ8CFH6. Positions 17-333.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini20 – 271252Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini295 – 33541UBAPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 UBA domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000048716.
    InParanoidiQ8CFH6.
    KOiK16311.
    PhylomeDBiQ8CFH6.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR017090. Ser/Thr_kinase_SIK1/2.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 2 hits.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50030. UBA. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8CFH6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR TTKTEVAIKI    50
    IDKSQLDAVN LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK 100
    NGEIFDYLAN HGRLNESEAR RKFWQILSAV DYCHGRKVVH RDLKAENLLL 150
    DNNMNIKIAD FGFGNFFKTG ELLATWCGSP PYAAPEVFEG QQYEGPQLDI 200
    WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM SEDCEHLIRR 250
    MLVLDPSKRL SIAQIKEHKW MLIEVPVQRP ILYPQEQENE PSIGEFNEQV 300
    LRLMHSLGID QQKTVESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL 350
    DGRQRRPSTI AEQTVAKAQT VGLPVTLHPP NVRLMRSTLL PQASNVEAFS 400
    FPTSSCQAEA AFMEEECVDT PKVNGCLLDP VPPVLVRKGC QSLPSSMMET 450
    SIDEGLETEG EAEEDPSQAF EAFQATRSGQ RRHTLSEVTN QLVVMPGAGK 500
    MFSMSDNPSL ESVDSEYDMG SAQRDLNFLE DSPSLKDIML ANQPSPRMTS 550
    PFISLRPANP AMQALSSQKR EAHNRSPVSF REGRRASDTS LTQGIVAFRQ 600
    HLQNLARTKG ILELNKVQLL YEQMGSNADP TLTSTAPQLQ DLSSSCPQEE 650
    ISQQQESVSS LSASMHPQLS PQQSLETQYL QHRLQKPNLL PKAQSPCPVY 700
    CKEPPRSLEQ QLQEHRLQQK RLFLQKQSQL QAYFNQMQIA ESSYPGPSQQ 750
    LALPHQETPL TSQQPPSFSL TQALSPVLEP SSEQMQFSSF LSQYPEMQLQ 800
    PLPSTPGPRA PPPLPSQLQQ HQQPPPPPPP PPPQQPGAAP TSLQFSYQTC 850
    ELPSTTSSVP NYPASCHYPV DGAQQSNLTG ADCPRSSGLQ DTASSYDPLA 900
    LSELPGLFDC EMVEAVDPQH NGVVSCLARE T 931
    Length:931
    Mass (Da):104,198
    Last modified:March 1, 2003 - v1
    Checksum:i5CF2FB8DCDC689F4
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB067780 mRNA. Translation: BAC53845.1.
    CCDSiCCDS40627.1.
    RefSeqiNP_848825.2. NM_178710.3.
    UniGeneiMm.104932.
    Mm.439989.

    Genome annotation databases

    GeneIDi235344.
    KEGGimmu:235344.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB067780 mRNA. Translation: BAC53845.1 .
    CCDSi CCDS40627.1.
    RefSeqi NP_848825.2. NM_178710.3.
    UniGenei Mm.104932.
    Mm.439989.

    3D structure databases

    ProteinModelPortali Q8CFH6.
    SMRi Q8CFH6. Positions 17-333.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 231647. 1 interaction.
    DIPi DIP-60734N.

    PTM databases

    PhosphoSitei Q8CFH6.

    Proteomic databases

    MaxQBi Q8CFH6.
    PaxDbi Q8CFH6.
    PRIDEi Q8CFH6.

    Protocols and materials databases

    DNASUi 235344.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 235344.
    KEGGi mmu:235344.

    Organism-specific databases

    CTDi 23235.
    MGIi MGI:2445031. Sik2.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000048716.
    InParanoidi Q8CFH6.
    KOi K16311.
    PhylomeDBi Q8CFH6.

    Miscellaneous databases

    NextBioi 382621.
    PROi Q8CFH6.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_SNF1LK2.
    Genevestigatori Q8CFH6.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR017090. Ser/Thr_kinase_SIK1/2.
    IPR015940. UBA/transl_elong_EF1B_N_euk.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
    SMARTi SM00220. S_TKc. 1 hit.
    [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.
    PS50030. UBA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2."
      Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J., Yamamoto H., Kasayama S., Muraoka M., Nonaka Y., Okamoto M.
      J. Biol. Chem. 278:18440-18447(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-49.
      Tissue: Adipose tissueImported.
    2. "Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade."
      Katoh Y., Takemori H., Lin X.-Z., Tamura M., Muraoka M., Satoh T., Tsuchiya Y., Min L., Doi J., Miyauchi A., Witters L.A., Nakamura H., Okamoto M.
      FEBS J. 273:2730-2748(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-175 AND SER-587, MUTAGENESIS OF LYS-49 AND THR-175.

    Entry informationi

    Entry nameiSIK2_MOUSE
    AccessioniPrimary (citable) accession number: Q8CFH6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 15, 2005
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 101 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, 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