SIK2_HUMAN
ID SIK2_HUMAN Reviewed; 926 AA.
AC Q9H0K1; A8K5B8; B0YJ94; O94878; Q17RV0; Q6AZE2; Q76N03; Q8NCV7; Q96CZ8;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Serine/threonine-protein kinase SIK2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:24129571};
DE AltName: Full=Qin-induced kinase;
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=KIAA0781 {ECO:0000312|EMBL:BAA34501.3}, QIK, SNF1LK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], ACTIVITY REGULATION, PHOSPHORYLATION AT
RP THR-175, AND MUTAGENESIS OF THR-175.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAA34501.3}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:BAA34501.3};
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [3] {ECO:0000305}
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAB66698.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6] {ECO:0000305, ECO:0000312|EMBL:BAB91442.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305, ECO:0000312|EMBL:BAB91442.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000305, ECO:0000312|EMBL:AAH78150.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Lung {ECO:0000312|EMBL:AAH13612.1}, and
RC Testis {ECO:0000312|EMBL:AAH78150.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9] {ECO:0000305, ECO:0000312|EMBL:BAB91442.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-926.
RA Takemori H.;
RT "A cDNA fragment encoding an active serine-kinase, Homo sapiens KIAA0781
RT protein.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP INTERACTION WITH CRTC2, AND FUNCTION.
RX PubMed=15454081; DOI=10.1016/j.cell.2004.09.015;
RA Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G.,
RA Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H.,
RA Okamoto M., Montminy M.;
RT "The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive
RT coincidence detector.";
RL Cell 119:61-74(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION.
RX PubMed=21084751; DOI=10.1172/jci41624;
RA Bricambert J., Miranda J., Benhamed F., Girard J., Postic C., Dentin R.;
RT "Salt-inducible kinase 2 links transcriptional coactivator p300
RT phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in
RT mice.";
RL J. Clin. Invest. 120:4316-4331(2010).
RN [15]
RP ACETYLATION AT LYS-53, AND FUNCTION.
RX PubMed=23322770; DOI=10.1074/jbc.m112.431239;
RA Yang F.C., Tan B.C., Chen W.H., Lin Y.H., Huang J.Y., Chang H.Y., Sun H.Y.,
RA Hsu P.H., Liou G.G., Shen J., Chang C.J., Han C.C., Tsai M.D., Lee S.C.;
RT "Reversible acetylation regulates salt-inducible kinase (SIK2) and its
RT function in autophagy.";
RL J. Biol. Chem. 288:6227-6237(2013).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=24129571; DOI=10.1074/jbc.m113.492199;
RA Yang F.C., Lin Y.H., Chen W.H., Huang J.Y., Chang H.Y., Su S.H., Wang H.T.,
RA Chiang C.Y., Hsu P.H., Tsai M.D., Tan B.C., Lee S.C.;
RT "Interaction between salt-inducible kinase 2 (SIK2) and p97/valosin-
RT containing protein (VCP) regulates endoplasmic reticulum (ER)-associated
RT protein degradation in mammalian cells.";
RL J. Biol. Chem. 288:33861-33872(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP FUNCTION.
RX PubMed=26983400; DOI=10.1038/srep23317;
RA Zhang Z.N., Gong L., Lv S., Li J., Tai X., Cao W., Peng B., Qu S., Li W.,
RA Zhang C., Luan B.;
RT "SIK2 regulates fasting-induced PPARalpha activity and ketogenesis through
RT p300.";
RL Sci. Rep. 6:23317-23317(2016).
RN [20]
RP PHOSPHORYLATION AT THR-484.
RX PubMed=30586628; DOI=10.1016/j.cellsig.2018.12.011;
RA Saell J., Negoita F., Hansson B., Kopietz F., Linder W., Pettersson A.M.L.,
RA Ekelund M., Laurencikiene J., Degerman E., Stenkula K.G., Goeransson O.;
RT "Insulin induces Thr484 phosphorylation and stabilization of SIK2 in
RT adipocytes.";
RL Cell. Signal. 55:73-80(2019).
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-458; GLN-809 AND LEU-825.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase that plays a role in many
CC biological processes such as fatty acid oxidation, autophagy, immune
CC response or glucose metabolism (PubMed:23322770, PubMed:26983400).
CC Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes,
CC potentially modulating the efficiency of insulin signal transduction.
CC Inhibits CREB activity by phosphorylating and repressing TORCs, the
CC CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and
CC thus inhibits its histone acetyltransferase activity (PubMed:21084751,
CC PubMed:26983400). In turn, regulates the DNA-binding ability of several
CC transcription factors such as PPARA or MLXIPL (PubMed:21084751,
CC PubMed:26983400). Also plays a role in thymic T-cell development (By
CC similarity). {ECO:0000250|UniProtKB:Q8CFH6,
CC ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751,
CC ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:24129571};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:14976552};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14976552};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-175.
CC {ECO:0000269|PubMed:14976552}.
CC -!- SUBUNIT: Interacts with and phosphorylates TORC2/CRTC2.
CC {ECO:0000269|PubMed:15454081}.
CC -!- INTERACTION:
CC Q9H0K1; Q9BV73: CEP250; NbExp=5; IntAct=EBI-1181664, EBI-1053100;
CC Q9H0K1; P60520: GABARAPL2; NbExp=3; IntAct=EBI-1181664, EBI-720116;
CC Q9H0K1; P27986: PIK3R1; NbExp=7; IntAct=EBI-1181664, EBI-79464;
CC Q9H0K1; P55072: VCP; NbExp=4; IntAct=EBI-1181664, EBI-355164;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:24129571}.
CC -!- PTM: Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39
CC (PubMed:14976552). Phosphorylated at Thr-484 in response to insulin in
CC adipocytes (PubMed:30586628). {ECO:0000269|PubMed:14976552,
CC ECO:0000269|PubMed:30586628}.
CC -!- PTM: Acetylation at Lys-53 inhibits kinase activity. Deacetylated by
CC HDAC6. {ECO:0000269|PubMed:23322770}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34501.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB018324; BAA34501.3; ALT_INIT; mRNA.
DR EMBL; AL136764; CAB66698.1; -; mRNA.
DR EMBL; AK291233; BAF83922.1; -; mRNA.
DR EMBL; EF445030; ACA06072.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67148.1; -; Genomic_DNA.
DR EMBL; BC013612; AAH13612.1; -; mRNA.
DR EMBL; BC078150; AAH78150.1; -; mRNA.
DR EMBL; BC113459; AAI13460.1; -; mRNA.
DR EMBL; BC117183; AAI17184.1; -; mRNA.
DR EMBL; AB084424; BAB91442.1; -; mRNA.
DR CCDS; CCDS8347.1; -.
DR RefSeq; NP_056006.1; NM_015191.2.
DR AlphaFoldDB; Q9H0K1; -.
DR SMR; Q9H0K1; -.
DR BioGRID; 116840; 96.
DR IntAct; Q9H0K1; 30.
DR STRING; 9606.ENSP00000305976; -.
DR BindingDB; Q9H0K1; -.
DR ChEMBL; CHEMBL5699; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9H0K1; -.
DR GuidetoPHARMACOLOGY; 2198; -.
DR GlyGen; Q9H0K1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H0K1; -.
DR PhosphoSitePlus; Q9H0K1; -.
DR BioMuta; SIK2; -.
DR DMDM; 59798973; -.
DR EPD; Q9H0K1; -.
DR jPOST; Q9H0K1; -.
DR MassIVE; Q9H0K1; -.
DR MaxQB; Q9H0K1; -.
DR PaxDb; Q9H0K1; -.
DR PeptideAtlas; Q9H0K1; -.
DR PRIDE; Q9H0K1; -.
DR ProteomicsDB; 80290; -.
DR Antibodypedia; 18251; 309 antibodies from 34 providers.
DR DNASU; 23235; -.
DR Ensembl; ENST00000304987.4; ENSP00000305976.3; ENSG00000170145.5.
DR GeneID; 23235; -.
DR KEGG; hsa:23235; -.
DR MANE-Select; ENST00000304987.4; ENSP00000305976.3; NM_015191.3; NP_056006.1.
DR UCSC; uc001plt.4; human.
DR CTD; 23235; -.
DR DisGeNET; 23235; -.
DR GeneCards; SIK2; -.
DR HGNC; HGNC:21680; SIK2.
DR HPA; ENSG00000170145; Low tissue specificity.
DR MIM; 608973; gene.
DR neXtProt; NX_Q9H0K1; -.
DR OpenTargets; ENSG00000170145; -.
DR PharmGKB; PA164725750; -.
DR VEuPathDB; HostDB:ENSG00000170145; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000156445; -.
DR HOGENOM; CLU_000288_87_0_1; -.
DR InParanoid; Q9H0K1; -.
DR OMA; QTVGPPM; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q9H0K1; -.
DR TreeFam; TF315213; -.
DR PathwayCommons; Q9H0K1; -.
DR SignaLink; Q9H0K1; -.
DR SIGNOR; Q9H0K1; -.
DR BioGRID-ORCS; 23235; 11 hits in 1110 CRISPR screens.
DR ChiTaRS; SIK2; human.
DR GeneWiki; SNF1LK2; -.
DR GenomeRNAi; 23235; -.
DR Pharos; Q9H0K1; Tchem.
DR PRO; PR:Q9H0K1; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H0K1; protein.
DR Bgee; ENSG00000170145; Expressed in choroid plexus epithelium and 216 other tissues.
DR ExpressionAtlas; Q9H0K1; baseline and differential.
DR Genevisible; Q9H0K1; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd14071; STKc_SIK; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR017090; Ser/Thr_kinase_SIK1/2.
DR InterPro; IPR034672; SIK.
DR InterPro; IPR015940; UBA.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF037014; Ser/Thr_PK_SNF1-like; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
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; Cytoplasm; Endoplasmic reticulum; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..926
FT /note="Serine/threonine-protein kinase SIK2"
FT /id="PRO_0000086662"
FT DOMAIN 20..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 295..335
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 644..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..896
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..767
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 801..816
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..838
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 142
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13131,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8CFH6,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 53
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000269|PubMed:23322770"
FT MOD_RES 175
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000269|PubMed:14976552"
FT MOD_RES 484
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:30586628"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFH6"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 458
FT /note="T -> I (in dbSNP:rs35789057)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041093"
FT VARIANT 809
FT /note="R -> Q (in dbSNP:rs34223841)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041094"
FT VARIANT 825
FT /note="P -> L (in dbSNP:rs55889697)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041095"
FT VARIANT 828
FT /note="P -> L (in dbSNP:rs45520245)"
FT /id="VAR_051667"
FT VARIANT 829
FT /note="P -> S (in dbSNP:rs45586732)"
FT /id="VAR_051668"
FT MUTAGEN 175
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex."
FT /evidence="ECO:0000269|PubMed:14976552"
FT MUTAGEN 175
FT /note="T->E: Constitutively active."
FT /evidence="ECO:0000269|PubMed:14976552"
FT CONFLICT 192
FT /note="Q -> H (in Ref. 5; BAF83922)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="E -> V (in Ref. 5; BAF83922)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 926 AA; 103915 MW; 9D7F9BF81FD65CCF CRC64;
MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR ITKTEVAIKI IDKSQLDAVN
LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK NGEIFDYLAN HGRLNESEAR
RKFWQILSAV DYCHGRKIVH RDLKAENLLL DNNMNIKIAD FGFGNFFKSG ELLATWCGSP
PYAAPEVFEG QQYEGPQLDI WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM
SEDCEHLIRR MLVLDPSKRL TIAQIKEHKW MLIEVPVQRP VLYPQEQENE PSIGEFNEQV
LRLMHSLGID QQKTIESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL DGRQRRPSTI
AEQTVAKAQT VGLPVTMHSP NMRLLRSALL PQASNVEAFS FPASGCQAEA AFMEEECVDT
PKVNGCLLDP VPPVLVRKGC QSLPSNMMET SIDEGLETEG EAEEDPAHAF EAFQSTRSGQ
RRHTLSEVTN QLVVMPGAGK IFSMNDSPSL DSVDSEYDMG SVQRDLNFLE DNPSLKDIML
ANQPSPRMTS PFISLRPTNP AMQALSSQKR EVHNRSPVSF REGRRASDTS LTQGIVAFRQ
HLQNLARTKG ILELNKVQLL YEQIGPEADP NLAPAAPQLQ DLASSCPQEE VSQQQESVST
LPASVHPQLS PRQSLETQYL QHRLQKPSLL SKAQNTCQLY CKEPPRSLEQ QLQEHRLQQK
RLFLQKQSQL QAYFNQMQIA ESSYPQPSQQ LPLPRQETPP PSQQAPPFSL TQPLSPVLEP
SSEQMQYSPF LSQYQEMQLQ PLPSTSGPRA APPLPTQLQQ QQPPPPPPPP PPRQPGAAPA
PLQFSYQTCE LPSAASPAPD YPTPCQYPVD GAQQSDLTGP DCPRSPGLQE APSSYDPLAL
SELPGLFDCE MLDAVDPQHN GYVLVN
