CRTC2_MOUSE
ID CRTC2_MOUSE Reviewed; 692 AA.
AC Q3U182; Q3TA52; Q8BH09;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=CREB-regulated transcription coactivator 2;
DE AltName: Full=Transducer of regulated cAMP response element-binding protein 2;
DE Short=TORC-2;
DE Short=Transducer of CREB protein 2;
GN Name=Crtc2; Synonyms=Torc2;
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 [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver, Mammary tumor, and Salivary gland;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-171, AND TISSUE
RP SPECIFICITY.
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 [4]
RP FUNCTION, PHOSPHORYLATION AT SER-171, AND SUBCELLULAR LOCATION.
RX PubMed=16308421; DOI=10.1126/science.1120781;
RA Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N., Depinho R.A.,
RA Montminy M., Cantley L.C.;
RT "The kinase LKB1 mediates glucose homeostasis in liver and therapeutic
RT effects of metformin.";
RL Science 310:1642-1646(2005).
RN [5]
RP INTERACTION WITH COP1, PHOSPHORYLATION AT SER-171, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF SER-171; VAL-214; PRO-215 AND LYS-628.
RX PubMed=17805301; DOI=10.1038/nature06128;
RA Dentin R., Liu Y., Koo S.-H., Hedrick S., Vargas T., Heredia J.,
RA Yates J. III, Montminy M.;
RT "Insulin modulates gluconeogenesis by inhibition of the coactivator
RT TORC2.";
RL Nature 449:366-369(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-171; SER-434;
RP SER-612; SER-622 AND SER-623, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=23699513; DOI=10.1523/jneurosci.4202-12.2013;
RA Sakamoto K., Norona F.E., Alzate-Correa D., Scarberry D., Hoyt K.R.,
RA Obrietan K.;
RT "Clock and light regulation of the CREB coactivator CRTC1 in the
RT suprachiasmatic circadian clock.";
RL J. Neurosci. 33:9021-9027(2013).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-161, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [11]
RP METHYLATION AT ARG-51; ARG-99; ARG-120; ARG-123; ARG-161 AND ARG-168.
RX PubMed=24570487; DOI=10.1126/scisignal.2004479;
RA Han H.S., Jung C.Y., Yoon Y.S., Choi S., Choi D., Kang G., Park K.G.,
RA Kim S.T., Koo S.H.;
RT "Arginine methylation of CRTC2 is critical in the transcriptional control
RT of hepatic glucose metabolism.";
RL Sci. Signal. 7:RA19-RA19(2014).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-171.
RX PubMed=29211348; DOI=10.1111/febs.14351;
RA Sonntag T., Vaughan J.M., Montminy M.;
RT "14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible
RT kinases (SIKs).";
RL FEBS J. 285:467-480(2018).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-70; THR-169 AND
RP SER-171, MUTAGENESIS OF SER-171 AND SER-275, AND INTERACTION WITH 14-3-3
RP PROTEINS.
RX PubMed=28235073; DOI=10.1371/journal.pone.0173013;
RA Sonntag T., Moresco J.J., Vaughan J.M., Matsumura S., Yates J.R. III,
RA Montminy M.;
RT "Analysis of a cAMP regulated coactivator family reveals an alternative
RT phosphorylation motif for AMPK family members.";
RL PLoS ONE 12:E0173013-E0173013(2017).
RN [14]
RP INTERACTION WITH YWHAE AND PPP3CA, AND PHOSPHORYLATION AT SER-171 AND
RP SER-275.
RX PubMed=30611118; DOI=10.1016/j.isci.2018.12.012;
RA Sonntag T., Ostojic J., Vaughan J.M., Moresco J.J., Yoon Y.S.,
RA Yates J.R. III, Montminy M.;
RT "Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A
RT Recruitment.";
RL IScience 11:134-145(2018).
CC -!- FUNCTION: Transcriptional coactivator for CREB1 which activates
CC transcription through both consensus and variant cAMP response element
CC (CRE) sites (PubMed:29211348). Acts as a coactivator, in the SIK/TORC
CC signaling pathway, being active when dephosphorylated
CC (PubMed:29211348). Acts independently of CREB1 'Ser-133'
CC phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates
CC gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling
CC pathway. Regulates the expression of specific genes such as the
CC steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of
CC mitochondrial biogenesis in muscle cells (By similarity).
CC {ECO:0000250|UniProtKB:Q53ET0, ECO:0000269|PubMed:16148943,
CC ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:29211348}.
CC -!- SUBUNIT: Binds, as a tetramer, through its N-terminal region, with the
CC bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is
CC essential for this interaction. Interaction, via its C-terminal, with
CC TAF4, enhances recruitment of TAF4 to CREB1. Interacts with SIK2 (By
CC similarity). Interacts with 14-3-3 proteins, YWHAB and YWHAG
CC (PubMed:28235073). Interacts (probably when phosphorylated at Ser-171)
CC with YWHAE (PubMed:30611118). Interacts with calmodulin-dependent
CC catalytic subunit PPP3CA/calcineurin A (PubMed:30611118). Interaction
CC with COP1 mediates nuclear export and degradation of CRTC2
CC (PubMed:17805301). {ECO:0000250|UniProtKB:Q53ET0,
CC ECO:0000269|PubMed:17805301, ECO:0000269|PubMed:28235073,
CC ECO:0000269|PubMed:30611118}.
CC -!- INTERACTION:
CC Q3U182; F6VAN0: Atf6; NbExp=2; IntAct=EBI-8018890, EBI-6171558;
CC Q3U182; Q9R1A8: Cop1; NbExp=3; IntAct=EBI-8018890, EBI-15656898;
CC Q3U182; P63328: Ppp3ca; NbExp=2; IntAct=EBI-8018890, EBI-397208;
CC Q3U182; P18850: ATF6; Xeno; NbExp=2; IntAct=EBI-8018890, EBI-852157;
CC Q3U182; P29994-1: Itpr1; Xeno; NbExp=2; IntAct=EBI-8018890, EBI-15683709;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16148943,
CC ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:17805301,
CC ECO:0000269|PubMed:29211348}. Nucleus {ECO:0000269|PubMed:16148943,
CC ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:17805301,
CC ECO:0000269|PubMed:29211348}. Note=Translocated from the nucleus to the
CC cytoplasm on interaction of the phosphorylated form with 14-3-3 protein
CC (By similarity). In response to cAMP levels and glucagon, relocated to
CC the nucleus (PubMed:16148943). {ECO:0000250|UniProtKB:Q53ET0,
CC ECO:0000269|PubMed:16148943}.
CC -!- TISSUE SPECIFICITY: Expressed in the suprachiasmatic nucleus (SCN) of
CC the brain. {ECO:0000269|PubMed:23699513}.
CC -!- PTM: Phosphorylation/dephosphorylation states of Ser-171 are required
CC for regulating transduction of CREB activity (PubMed:29211348).
CC CRTCs/TORCs are inactive when phosphorylated, and active when
CC dephosphorylated at this site (PubMed:29211348). This primary site of
CC phosphorylation, is regulated by cAMP and calcium levels and is
CC dependent on the phosphorylation of SIKs (SIK1 and SIK2) by LKB1 (By
CC similarity). Following adenylyl cyclase activation, dephosphorylated at
CC Ser-171 by PPP3CA/calcineurin A resulting in CRTC2 dissociation from
CC 14-3-3 proteins and PPP3CA (PubMed:30611118). Phosphorylation at Ser-
CC 275 by MARK2 is induced under low glucose conditions and
CC dephosphorylated in response to glucose influx (By similarity). Both
CC insulin and AMPK increase this phosphorylation of CRTC2 while glucagon
CC suppresses it (By similarity). Phosphorylation at Ser-275 promotes
CC interaction with 14-3-3 proteins and translocation to the cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:Q53ET0,
CC ECO:0000269|PubMed:29211348, ECO:0000269|PubMed:30611118}.
CC -!- PTM: Asymmetric dimethylation of arginine resisues by PRMT6 enhances
CC the association of CRTC2 with CREB on the promoters of gluconeogenic
CC genes. {ECO:0000269|PubMed:24570487}.
CC -!- SIMILARITY: Belongs to the TORC family. {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; AK156192; BAE33618.1; -; mRNA.
DR EMBL; AK172084; BAE42818.1; -; mRNA.
DR EMBL; BC023831; AAH23831.1; -; mRNA.
DR EMBL; BC032183; AAH32183.1; -; mRNA.
DR EMBL; BC033300; AAH33300.1; -; mRNA.
DR CCDS; CCDS38501.1; -.
DR RefSeq; NP_083157.1; NM_028881.2.
DR PDB; 5ZK1; X-ray; 3.05 A; C=17-58.
DR PDB; 5ZKO; X-ray; 3.05 A; G/H=1-80.
DR PDBsum; 5ZK1; -.
DR PDBsum; 5ZKO; -.
DR AlphaFoldDB; Q3U182; -.
DR SMR; Q3U182; -.
DR BioGRID; 216678; 9.
DR DIP; DIP-46162N; -.
DR ELM; Q3U182; -.
DR IntAct; Q3U182; 11.
DR STRING; 10090.ENSMUSP00000029545; -.
DR iPTMnet; Q3U182; -.
DR PhosphoSitePlus; Q3U182; -.
DR EPD; Q3U182; -.
DR jPOST; Q3U182; -.
DR MaxQB; Q3U182; -.
DR PaxDb; Q3U182; -.
DR PeptideAtlas; Q3U182; -.
DR PRIDE; Q3U182; -.
DR ProteomicsDB; 285309; -.
DR Antibodypedia; 34141; 572 antibodies from 40 providers.
DR DNASU; 74343; -.
DR Ensembl; ENSMUST00000029545; ENSMUSP00000029545; ENSMUSG00000027936.
DR GeneID; 74343; -.
DR KEGG; mmu:74343; -.
DR UCSC; uc008qbt.2; mouse.
DR CTD; 200186; -.
DR MGI; MGI:1921593; Crtc2.
DR VEuPathDB; HostDB:ENSMUSG00000027936; -.
DR eggNOG; ENOG502QVWA; Eukaryota.
DR GeneTree; ENSGT00390000010652; -.
DR InParanoid; Q3U182; -.
DR OMA; YPRHIID; -.
DR OrthoDB; 1118500at2759; -.
DR PhylomeDB; Q3U182; -.
DR TreeFam; TF321571; -.
DR BioGRID-ORCS; 74343; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q3U182; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q3U182; protein.
DR Bgee; ENSMUSG00000027936; Expressed in retinal neural layer and 208 other tissues.
DR ExpressionAtlas; Q3U182; baseline and differential.
DR Genevisible; Q3U182; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0006094; P:gluconeogenesis; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IGI:MGI.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:1901998; P:toxin transport; IMP:MGI.
DR InterPro; IPR024786; TORC.
DR InterPro; IPR024785; TORC_C.
DR InterPro; IPR024784; TORC_M.
DR InterPro; IPR024783; TORC_N.
DR PANTHER; PTHR13589; PTHR13589; 1.
DR Pfam; PF12886; TORC_C; 1.
DR Pfam; PF12885; TORC_M; 1.
DR Pfam; PF12884; TORC_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Cytoplasm; Isopeptide bond;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT CHAIN 2..692
FT /note="CREB-regulated transcription coactivator 2"
FT /id="PRO_0000318529"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..215
FT /note="Required for interaction with COP1"
FT /evidence="ECO:0000269|PubMed:17805301"
FT REGION 283..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 272..288
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 628
FT /note="Required for ubiquitination and degradation"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 51
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28235073,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 99
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487"
FT MOD_RES 120
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487"
FT MOD_RES 123
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 161
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487,
FT ECO:0007744|PubMed:24129315"
FT MOD_RES 168
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000269|PubMed:24570487"
FT MOD_RES 169
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:28235073"
FT MOD_RES 171
FT /note="Phosphoserine; by AMPK, MARK2, SIK1 and SIK2"
FT /evidence="ECO:0000269|PubMed:16148943,
FT ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:17805301,
FT ECO:0000269|PubMed:28235073, ECO:0000269|PubMed:29211348,
FT ECO:0000269|PubMed:30611118, ECO:0007744|PubMed:21183079"
FT MOD_RES 192
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30611118"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 489
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 502
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 622
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 235
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MUTAGEN 171
FT /note="S->A: Up-regulates CREB transcription factor
FT activity. Reduces interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:28235073"
FT MUTAGEN 171
FT /note="S->A: Up-regulates CREB-mediated gluconeogenic gene
FT expression. No degradation of CRTC2. Loss of SIK2-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17805301"
FT MUTAGEN 213
FT /note="K->R: No effect on COP1-mediated degradation of
FT TORC1 under forksolin stimulation."
FT MUTAGEN 214
FT /note="V->A: No interaction with COP1. Inhibition of
FT degradation under exposure to FSK/INS."
FT /evidence="ECO:0000269|PubMed:17805301"
FT MUTAGEN 215
FT /note="P->A: No interaction with COP1. Inhibition of
FT degradation under exposure to FSK/INS."
FT /evidence="ECO:0000269|PubMed:17805301"
FT MUTAGEN 275
FT /note="S->A: Does not affect interaction with 14-3-3
FT proteins."
FT /evidence="ECO:0000269|PubMed:28235073"
FT MUTAGEN 628
FT /note="K->R: Translocates to the nucleus and no COP1-
FT mediated degradation."
FT /evidence="ECO:0000269|PubMed:17805301"
FT CONFLICT 195
FT /note="S -> G (in Ref. 1; BAE33618)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="G -> R (in Ref. 1; BAE42818)"
FT /evidence="ECO:0000305"
FT HELIX 22..44
FT /evidence="ECO:0007829|PDB:5ZK1"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:5ZK1"
SQ SEQUENCE 692 AA; 73216 MW; 5BCBC416D45CFAD8 CRC64;
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST RLQAQKLRLA
YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH HGLVERVQRD ARRMVSPLRR
YPRHIDSSPY SPAYLSPPPE SGWRRMMPWG NLPAEKGQLF RLPSALNRTS SDSALHTSVM
NPNPQDTYPG PTPPSVLPSR RGGGFLDGEM DAKVPAIEEN VVDDKHLLKP WDAKKLSSSS
SRPRSCEVPG INIFPSPDQP ANVPVLPPAM NTGGSLPDLT NLHFPPPLPT PLDPEETVYP
SLSGGNSTTN LTHTMTHLGI SGGLGLGPSY DVPGLHSPLS HPSLQSSLSN PNLQASLSSP
QPQLQGSHSH PSLPASSLAH HALPTTSLGH PSLSAPALSS SSSSSSTSSP VLSAPPYPAS
TPGASPRHRR VPLSPLSLPA GPADARRSQQ QLPKQFSPTM SPTLSSITQG VPLDTSKLPT
DQRLPPYPYS PPSLVIPTHP PTPKSLQQLP SQACLVQPSG GQPPGRQPHY GALYPPGSSG
HGQQPYHRPI NDFSLGNLEQ FNMESPSTSL VLDPPAFSEG PGFLGSEGSM SGPQDPHVLN
HQNLTHCSRH GSGPNIILTG DSSPGFSKEI AAALAGVPGF EVSASGLELG LGLEDELRME
PLGLEGLTML SDPCALLPDP AVEDSFRSDR LQ
