SIK1_MOUSE
ID SIK1_MOUSE Reviewed; 779 AA.
AC Q60670; Q3UR46;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase SIK1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:15177563, ECO:0000269|PubMed:16148943, ECO:0000269|PubMed:17468767, ECO:0000269|PubMed:19244231};
DE AltName: Full=HRT-20;
DE AltName: Full=Myocardial SNF1-like kinase;
DE AltName: Full=Salt-inducible kinase 1;
DE Short=SIK-1;
DE AltName: Full=Serine/threonine-protein kinase SNF1-like kinase 1;
DE Short=Serine/threonine-protein kinase SNF1LK;
GN Name=Sik1; Synonyms=Msk, Sik, Snf1lk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=7893599; DOI=10.1016/0925-4773(94)90056-6;
RA Ruiz J.C., Conlon F.L., Robertson E.J.;
RT "Identification of novel protein kinases expressed in the myocardium of the
RT developing mouse heart.";
RL Mech. Dev. 48:153-164(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-577, AND MUTAGENESIS
RP OF THR-268; THR-475 AND SER-577.
RX PubMed=12200423; DOI=10.1074/jbc.m204602200;
RA Takemori H., Katoh Y., Horike N., Doi J., Okamoto M.;
RT "ACTH-induced nucleocytoplasmic translocation of salt-inducible kinase.
RT Implication in the protein kinase A-activated gene transcription in mouse
RT adrenocortical tumor cells.";
RL J. Biol. Chem. 277:42334-42343(2002).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN RK-RICH REGION, AND MUTAGENESIS OF
RP 593-ARG-LYS-594; 597-ARG--LYS-599; 606-LYS--LYS-608; ILE-607 AND LEU-610.
RX PubMed=15511237; DOI=10.1111/j.1432-1033.2004.04372.x;
RA Katoh Y., Takemori H., Min L., Muraoka M., Doi J., Horike N., Okamoto M.;
RT "Salt-inducible kinase-1 represses cAMP response element-binding protein
RT activity both in the nucleus and in the cytoplasm.";
RL Eur. J. Biochem. 271:4307-4319(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF LYS-56.
RX PubMed=15177563; DOI=10.1016/j.ygeno.2003.12.007;
RA Stephenson A., Huang G.Y., Nguyen N.T., Reuter S., McBride J.L., Ruiz J.C.;
RT "snf1lk encodes a protein kinase that may function in cell cycle
RT regulation.";
RL Genomics 83:1105-1115(2004).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF CRTC2, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16148943; DOI=10.1038/nature03967;
RA Koo S.-H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S.,
RA Hedrick S., Xu W., Boussouar F., Brindle P., Takemori H., Montminy M.;
RT "The CREB coactivator TORC2 is a key regulator of fasting glucose
RT metabolism.";
RL Nature 437:1109-1111(2005).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP THR-182 AND SER-577, AND MUTAGENESIS OF LYS-56; THR-182 AND SER-577.
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 LKB1-
RT SIK signaling cascade.";
RL FEBS J. 273:2730-2748(2006).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF HDAC4 AND HDAC5, CATALYTIC ACTIVITY,
RP INDUCTION, PHOSPHORYLATION AT SER-577, AND MUTAGENESIS OF LYS-56 AND
RP SER-577.
RX PubMed=17468767; DOI=10.1038/nm1573;
RA Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T.,
RA Shelton G.D., Montminy M.;
RT "SIK1 is a class II HDAC kinase that promotes survival of skeletal
RT myocytes.";
RL Nat. Med. 13:597-603(2007).
RN [9]
RP FUNCTION.
RX PubMed=19622832; DOI=10.1126/scisignal.2000369;
RA Cheng H., Liu P., Wang Z.C., Zou L., Santiago S., Garbitt V., Gjoerup O.V.,
RA Iglehart J.D., Miron A., Richardson A.L., Hahn W.C., Zhao J.J.;
RT "SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis.";
RL Sci. Signal. 2:RA35-RA35(2009).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF SREBF1, AND CATALYTIC ACTIVITY.
RX PubMed=19244231; DOI=10.1074/jbc.m900096200;
RA Yoon Y.S., Seo W.Y., Lee M.W., Kim S.T., Koo S.H.;
RT "Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-
RT 1c phosphorylation.";
RL J. Biol. Chem. 284:10446-10452(2009).
RN [11]
RP FUNCTION.
RX PubMed=20140255; DOI=10.1371/journal.pone.0009029;
RA Romito A., Lonardo E., Roma G., Minchiotti G., Ballabio A., Cobellis G.;
RT "Lack of sik1 in mouse embryonic stem cells impairs cardiomyogenesis by
RT down-regulating the cyclin-dependent kinase inhibitor p57kip2.";
RL PLoS ONE 5:E9029-E9029(2010).
RN [12]
RP FUNCTION.
RX PubMed=23993098; DOI=10.1016/j.cell.2013.08.004;
RA Jagannath A., Butler R., Godinho S.I., Couch Y., Brown L.A.,
RA Vasudevan S.R., Flanagan K.C., Anthony D., Churchill G.C., Wood M.J.,
RA Steiner G., Ebeling M., Hossbach M., Wettstein J.G., Duffield G.E.,
RA Gatti S., Hankins M.W., Foster R.G., Peirson S.N.;
RT "The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.";
RL Cell 154:1100-1111(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as cell cycle regulation, gluconeogenesis and lipogenesis
CC regulation, muscle growth and differentiation and tumor suppression.
CC Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1 and
CC CRTC2/TORC2. Acts as a tumor suppressor and plays a key role in
CC p53/TP53-dependent anoikis, a type of apoptosis triggered by cell
CC detachment: required for phosphorylation of p53/TP53 in response to
CC loss of adhesion and is able to suppress metastasis. Part of a sodium-
CC sensing signaling network, probably by mediating phosphorylation of
CC PPME1: following increases in intracellular sodium, SIK1 is activated
CC by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A
CC (PP2A), leading to dephosphorylation of sodium/potassium-transporting
CC ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a
CC regulator of muscle cells by phosphorylating and inhibiting class II
CC histone deacetylases HDAC4 and HDAC5, leading to promote expression of
CC MEF2 target genes in myocytes. Also required during cardiomyogenesis by
CC regulating the exit of cardiomyoblasts from the cell cycle via down-
CC regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic
CC gluconeogenesis by phosphorylating and repressing the CREB-specific
CC coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB
CC activity. Also regulates hepatic lipogenesis by phosphorylating and
CC inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-
CC induced entrainment of the circadian clock by attenuating PER1
CC induction; represses CREB-mediated transcription of PER1 by
CC phosphorylating and deactivating CRTC1/TORC1.
CC {ECO:0000269|PubMed:12200423, ECO:0000269|PubMed:15177563,
CC ECO:0000269|PubMed:15511237, ECO:0000269|PubMed:16148943,
CC ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17468767,
CC ECO:0000269|PubMed:19244231, ECO:0000269|PubMed:19622832,
CC ECO:0000269|PubMed:20140255, ECO:0000269|PubMed:23993098}.
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:15177563, ECO:0000269|PubMed:16148943,
CC ECO:0000269|PubMed:17468767, ECO:0000269|PubMed:19244231};
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:15177563,
CC ECO:0000269|PubMed:16148943, ECO:0000269|PubMed:17468767,
CC ECO:0000269|PubMed:19244231};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-182. Also
CC activated by phosphorylation on Thr-322 in response to increases in
CC intracellular sodium in parallel with elevations in intracellular
CC calcium through the reversible sodium/calcium exchanger.
CC {ECO:0000269|PubMed:16817901}.
CC -!- SUBUNIT: Interacts (when phosphorylated on Thr-182 and Ser-186) with
CC YWHAZ. Interacts with ATP1A1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Following ACTH
CC (adrenocorticotropic hormone) treatment and subsequent phosphorylation
CC by PKA, translocates to the cytoplasm, where it binds to YWHAZ.
CC -!- TISSUE SPECIFICITY: Expressed in lung, skin, ovary, heart and stomach.
CC No expression in brain, liver or adult skeletal muscle but is present
CC in skeletal muscle progenitor cells of the somite beginning at 9.5 dpc.
CC Present at 8.0 dpc in the monolayer of presumptive myocardial cells but
CC rapidly down-regulated at 8.5 dpc upon primitive ventricle formation,
CC although still present in myocardial cells that will populate the
CC primitive atrium and bulbus cordis. At 9.5 dpc expression is down-
CC regulated in the primitive atrium but observed in the sinus venosus and
CC truncus arteriosus. {ECO:0000269|PubMed:15177563,
CC ECO:0000269|PubMed:7893599}.
CC -!- INDUCTION: Expression is stimulated by CREB1 in myocytes; direct target
CC of CREB1. {ECO:0000269|PubMed:17468767}.
CC -!- DOMAIN: The RK-rich region determines the subcellular location.
CC {ECO:0000269|PubMed:15511237}.
CC -!- PTM: Phosphorylated at Thr-182 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39, leading to its
CC activation. Phosphorylation at Thr-182 promotes autophosphorylation at
CC Ser-186, which is required for sustained activity. Autophosphorylation
CC at Ser-186 is maintained by sequential phosphorylation at Thr-182 by
CC GSK3-beta. GSK3-beta cannot initiate phosphorylation at Thr-182, it can
CC only maintain it. Phosphorylation at Ser-577 by PKA promotes
CC translocation to the cytoplasm. Phosphorylation at Thr-322 by CaMK1
CC following intracellular sodium concentration leads to activation.
CC {ECO:0000269|PubMed:12200423, ECO:0000269|PubMed:16817901,
CC ECO:0000269|PubMed:17468767}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. AMPK subfamily. {ECO:0000305}.
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DR EMBL; U11494; AAA67926.2; -; mRNA.
DR EMBL; AK141817; BAE24842.1; -; mRNA.
DR CCDS; CCDS37552.1; -.
DR PIR; I49072; I49072.
DR RefSeq; NP_034961.2; NM_010831.3.
DR AlphaFoldDB; Q60670; -.
DR SMR; Q60670; -.
DR BioGRID; 201531; 3.
DR IntAct; Q60670; 1.
DR STRING; 10090.ENSMUSP00000024839; -.
DR iPTMnet; Q60670; -.
DR PhosphoSitePlus; Q60670; -.
DR MaxQB; Q60670; -.
DR PaxDb; Q60670; -.
DR PRIDE; Q60670; -.
DR ProteomicsDB; 261041; -.
DR DNASU; 17691; -.
DR Ensembl; ENSMUST00000024839; ENSMUSP00000024839; ENSMUSG00000024042.
DR GeneID; 17691; -.
DR KEGG; mmu:17691; -.
DR UCSC; uc008bvr.1; mouse.
DR CTD; 150094; -.
DR MGI; MGI:104754; Sik1.
DR VEuPathDB; HostDB:ENSMUSG00000024042; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000154989; -.
DR HOGENOM; CLU_000288_87_2_1; -.
DR InParanoid; Q60670; -.
DR OMA; LHISAGP; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q60670; -.
DR TreeFam; TF315213; -.
DR BioGRID-ORCS; 17691; 2 hits in 61 CRISPR screens.
DR ChiTaRS; Nop58; mouse.
DR PRO; PR:Q60670; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q60670; protein.
DR Bgee; ENSMUSG00000024042; Expressed in granulocyte and 210 other tissues.
DR Genevisible; Q60670; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI: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:0043276; P:anoikis; IMP:BHF-UCL.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0032792; P:negative regulation of CREB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0010868; P:negative regulation of triglyceride biosynthetic process; IDA:UniProtKB.
DR GO; GO:2000210; P:positive regulation of anoikis; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IEP:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0010830; P:regulation of myotube differentiation; IDA:UniProtKB.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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 ATP-binding; Biological rhythms; Cell cycle; Cytoplasm;
KW Developmental protein; Differentiation; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..779
FT /note="Serine/threonine-protein kinase SIK1"
FT /id="PRO_0000086660"
FT DOMAIN 27..278
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 303..343
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 350..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 586..612
FT /note="RK-rich region"
FT REGION 621..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 33..41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 182
FT /note="Phosphothreonine; by LKB1 and GSK3-beta"
FT /evidence="ECO:0000269|PubMed:16817901"
FT MOD_RES 186
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P57059"
FT MOD_RES 322
FT /note="Phosphothreonine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:Q9R1U5"
FT MOD_RES 577
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12200423,
FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17468767"
FT MUTAGEN 56
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15177563,
FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17468767"
FT MUTAGEN 182
FT /note="T->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:16817901"
FT MUTAGEN 182
FT /note="T->E: Low levels of constitutive activity."
FT /evidence="ECO:0000269|PubMed:16817901"
FT MUTAGEN 268
FT /note="T->A: Does not affect phosphorylation by PKA and
FT nuclear export following ACTH treatment."
FT /evidence="ECO:0000269|PubMed:12200423"
FT MUTAGEN 475
FT /note="T->A: Does not affect phosphorylation by PKA and
FT nuclear export following ACTH treatment."
FT /evidence="ECO:0000269|PubMed:12200423"
FT MUTAGEN 577
FT /note="S->A: Abolishes phosphorylation by PKA and impairs
FT nuclear export following ACTH treatment."
FT /evidence="ECO:0000269|PubMed:12200423,
FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17468767"
FT MUTAGEN 577
FT /note="S->A: Constitutively active."
FT /evidence="ECO:0000269|PubMed:12200423,
FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17468767"
FT MUTAGEN 593..594
FT /note="RK->AA: Localizes mainly in cytoplasm and not in
FT nucleus."
FT /evidence="ECO:0000269|PubMed:15511237"
FT MUTAGEN 597..599
FT /note="RTK->ATA: Localizes mainly in cytoplasm and not in
FT nucleus."
FT /evidence="ECO:0000269|PubMed:15511237"
FT MUTAGEN 606..608
FT /note="KIK->AIA: Localizes mainly in cytoplasm and not in
FT nucleus."
FT /evidence="ECO:0000269|PubMed:15511237"
FT MUTAGEN 607
FT /note="I->A: Localizes mainly in cytoplasm and not in
FT nucleus; when associated with D-483 and A-610."
FT /evidence="ECO:0000269|PubMed:15511237"
FT MUTAGEN 610
FT /note="L->A: Localizes mainly in cytoplasm and not in
FT nucleus; when associated with D-483 and A-607."
FT /evidence="ECO:0000269|PubMed:15511237"
FT CONFLICT 183..184
FT /note="WC -> CV (in Ref. 1; AAA67926)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 779 AA; 85115 MW; 9C4D25CCF0C0D06D CRC64;
MVIMSEFSAV PSGTGQGQQK PLRVGFYDVE RTLGKGNFAV VKLARHRVTK TQVAIKIIDK
TRLDSSNLEK IYREVQLMKL LNHPNIIKLY QVMETKDMLY IVTEFAKNGE MFDYLTSNGH
LSENEARQKF WQILSAVEYC HNHHIVHRDL KTENLLLDSN MDIKLADFGF GNFYKPGEPL
STWCGSPPYA APEVFEGKEY EGPQLDVWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR
FRIPFFMSQD CETLIRRMLV VDPAKRITIA QIRQHRWMQA DPTLLQQDDP AFDMQGYTSN
LGDYNEQVLG IMQALGIDRQ RTIESLQNSS YNHFAAIYYL LLERLKEHRS AQPSSRPTPA
PTRQPQLRSS DLSSLEVPQE ILPCDPFRPS LLCPQPQALA QSVLQAEIDC DLHSSLQPLL
FPLDTNCSGV FRHRSISPSS LLDTAISEEA RQGPSLEEEQ EVQEPLPGST GRRHTLAEVS
THFSPLNPPC IIVSSSATAS PSEGTSSDSC LPFSASEGPA GLGSGLATPG LLGTSSPVRL
ASPFLGSQSA TPVLQTQAGL GTAVLPPVSF QEGRRASDTS LTQGLKAFRQ QLRKNARTKG
FLGLNKIKGL ARQVCQSSVR TPRGGMSTFH TPAPSSGLQG CTTSNREGRS LLEEVLHQQR
LLQLQHHSST AAASSGCQQG PQLSPVPYVL APCDSLLVSG IPLLPTPLLQ AGMSPVASAA
HLLDTHLHIS AGPVALPTGP LPQCLTRLSP GCDPAGLPQG DCEMEDLTSG QRGTFVLVQ
