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 27-MAR-2024, entry version 192. 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; GN 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 Testis RC {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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 102. DR IntAct; Q9H0K1; 35. 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; 9606-ENSP00000305976; -. DR PeptideAtlas; Q9H0K1; -. DR ProteomicsDB; 80290; -. DR Pumba; Q9H0K1; -. DR Antibodypedia; 18251; 326 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 AGR; HGNC:21680; -. 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; PPFISIR; -. DR OrthoDB; 5475340at2759; -. DR PhylomeDB; Q9H0K1; -. DR TreeFam; TF315213; -. DR PathwayCommons; Q9H0K1; -. DR SignaLink; Q9H0K1; -. DR SIGNOR; Q9H0K1; -. DR BioGRID-ORCS; 23235; 12 hits in 1193 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 218 other cell types or tissues. DR ExpressionAtlas; Q9H0K1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProt. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. 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; IDA:UniProt. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. 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 CDD; cd14409; UBA_SIK2; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1. DR PANTHER; PTHR24346:SF38; NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR PIRSF; PIRSF037014; Ser/Thr_PK_SNF1-like; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q9H0K1; HS. 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 //