ID   SIK2_MOUSE              Reviewed;         931 AA.
AC   Q8CFH6;
DT   15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   22-JAN-2014, entry version 96.
DE   RecName: Full=Serine/threonine-protein kinase SIK2;
DE            EC=2.7.11.1;
DE   AltName: Full=Salt-inducible kinase 2;
DE            Short=SIK-2;
DE   AltName: Full=Serine/threonine-protein kinase SNF1-like kinase 2;
GN   Name=Sik2; Synonyms=Snf1lk2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND MUTAGENESIS OF LYS-49.
RC   TISSUE=Adipose tissue;
RX   PubMed=12624099; DOI=10.1074/jbc.M211770200;
RA   Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J.,
RA   Yamamoto H., Kasayama S., Muraoka M., Nonaka Y., Okamoto M.;
RT   "Adipose-specific expression, phosphorylation of Ser794 in insulin
RT   receptor substrate-1, and activation in diabetic animals of salt-
RT   inducible kinase-2.";
RL   J. Biol. Chem. 278:18440-18447(2003).
RN   [2]
RP   FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-175 AND SER-587,
RP   AND MUTAGENESIS OF LYS-49 AND THR-175.
RX   PubMed=16817901; DOI=10.1111/j.1742-4658.2006.05291.x;
RA   Katoh Y., Takemori H., Lin X.-Z., Tamura M., Muraoka M., Satoh T.,
RA   Tsuchiya Y., Min L., Doi J., Miyauchi A., Witters L.A., Nakamura H.,
RA   Okamoto M.;
RT   "Silencing the constitutive active transcription factor CREB by the
RT   LKB1-SIK signaling cascade.";
RL   FEBS J. 273:2730-2748(2006).
CC   -!- FUNCTION: Phosphorylates 'Ser-789' of IRS1 in insulin-stimulated
CC       adipocytes, potentially modulating the efficiency of insulin
CC       signal transduction. Inhibits CREB activity by phosphorylating and
CC       repressing TORCs, the CREB-specific coactivators.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- COFACTOR: Magnesium.
CC   -!- ENZYME REGULATION: Activated by phosphorylation on Thr-175 (By
CC       similarity).
CC   -!- SUBUNIT: Interacts with and phosphorylates TORC2/CRTC2 (By
CC       similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Present in both white and brown adipose
CC       tissues with levels increasing during adipocyte differentiation.
CC       Lower levels observed in the testis.
CC   -!- PTM: Phosphorylated at Thr-175 by STK11/LKB1 in complex with
CC       STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (By
CC       similarity).
CC   -!- PTM: Acetylation at Lys-53 inhibits kinase activity. Deacetylated
CC       by HDAC6 (By similarity).
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC       Ser/Thr protein kinase family. SNF1 subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- SIMILARITY: Contains 1 UBA domain.
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DR   EMBL; AB067780; BAC53845.1; -; mRNA.
DR   RefSeq; NP_848825.2; NM_178710.3.
DR   UniGene; Mm.104932; -.
DR   ProteinModelPortal; Q8CFH6; -.
DR   SMR; Q8CFH6; 17-333.
DR   PhosphoSite; Q8CFH6; -.
DR   PaxDb; Q8CFH6; -.
DR   PRIDE; Q8CFH6; -.
DR   DNASU; 235344; -.
DR   GeneID; 235344; -.
DR   KEGG; mmu:235344; -.
DR   CTD; 23235; -.
DR   MGI; MGI:2445031; Sik2.
DR   eggNOG; COG0515; -.
DR   HOGENOM; HOG000048716; -.
DR   InParanoid; Q8CFH6; -.
DR   KO; K16311; -.
DR   NextBio; 382621; -.
DR   PRO; PR:Q8CFH6; -.
DR   CleanEx; MM_SNF1LK2; -.
DR   Genevestigator; Q8CFH6; -.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI.
DR   GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR   GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR017090; Ser/Thr_kinase_SIK1/2.
DR   InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR   Pfam; PF00069; Pkinase; 1.
DR   PIRSF; PIRSF037014; Ser/Thr_PK_SNF1-like; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 2.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50030; UBA; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW   Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN         1    931       Serine/threonine-protein kinase SIK2.
FT                                /FTId=PRO_0000086663.
FT   DOMAIN       20    271       Protein kinase.
FT   DOMAIN      295    335       UBA.
FT   NP_BIND      26     34       ATP (By similarity).
FT   ACT_SITE    142    142       Proton acceptor (By similarity).
FT   BINDING      49     49       ATP.
FT   MOD_RES      25     25       Phosphothreonine (By similarity).
FT   MOD_RES      53     53       N6-acetyllysine; by EP300 (By
FT                                similarity).
FT   MOD_RES     175    175       Phosphothreonine (By similarity).
FT   MOD_RES     587    587       Phosphoserine (By similarity).
FT   MUTAGEN      49     49       K->M: Loss of kinase activity.
FT   MUTAGEN     175    175       T->E: Low levels of constitutive
FT                                activity.
SQ   SEQUENCE   931 AA;  104198 MW;  5CF2FB8DCDC689F4 CRC64;
     MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR TTKTEVAIKI IDKSQLDAVN
     LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK NGEIFDYLAN HGRLNESEAR
     RKFWQILSAV DYCHGRKVVH RDLKAENLLL DNNMNIKIAD FGFGNFFKTG ELLATWCGSP
     PYAAPEVFEG QQYEGPQLDI WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM
     SEDCEHLIRR MLVLDPSKRL SIAQIKEHKW MLIEVPVQRP ILYPQEQENE PSIGEFNEQV
     LRLMHSLGID QQKTVESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL DGRQRRPSTI
     AEQTVAKAQT VGLPVTLHPP NVRLMRSTLL PQASNVEAFS FPTSSCQAEA AFMEEECVDT
     PKVNGCLLDP VPPVLVRKGC QSLPSSMMET SIDEGLETEG EAEEDPSQAF EAFQATRSGQ
     RRHTLSEVTN QLVVMPGAGK MFSMSDNPSL ESVDSEYDMG SAQRDLNFLE DSPSLKDIML
     ANQPSPRMTS PFISLRPANP AMQALSSQKR EAHNRSPVSF REGRRASDTS LTQGIVAFRQ
     HLQNLARTKG ILELNKVQLL YEQMGSNADP TLTSTAPQLQ DLSSSCPQEE ISQQQESVSS
     LSASMHPQLS PQQSLETQYL QHRLQKPNLL PKAQSPCPVY CKEPPRSLEQ QLQEHRLQQK
     RLFLQKQSQL QAYFNQMQIA ESSYPGPSQQ LALPHQETPL TSQQPPSFSL TQALSPVLEP
     SSEQMQFSSF LSQYPEMQLQ PLPSTPGPRA PPPLPSQLQQ HQQPPPPPPP PPPQQPGAAP
     TSLQFSYQTC ELPSTTSSVP NYPASCHYPV DGAQQSNLTG ADCPRSSGLQ DTASSYDPLA
     LSELPGLFDC EMVEAVDPQH NGVVSCLARE T
//