ID CRTC2_HUMAN Reviewed; 693 AA. AC Q53ET0; Q6UUV8; Q7Z3X7; Q8N332; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 2. DT 27-MAR-2024, entry version 144. 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 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] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT CYS-379, AND FUNCTION. RX PubMed=14506290; DOI=10.1073/pnas.1932773100; RA Iourgenko V., Zhang W., Mickanin C., Daly I., Jiang C., Hexham J.M., RA Orth A.P., Miraglia L., Meltzer J., Garza D., Chirn G.-W., McWhinnie E., RA Cohen D., Skelton J., Terry R., Yu Y., Bodian D., Buxton F.P., Zhu J., RA Song C., Labow M.A.; RT "Identification of a family of cAMP response element-binding protein RT coactivators by genome-scale functional analysis in mammalian cells."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC TISSUE=Brain; RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=PNS, and Urinary bladder; 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 [5] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=14536081; DOI=10.1016/j.molcel.2003.08.013; RA Conkright M.D., Canettieri G., Screaton R., Guzman E., Miraglia L., RA Hogenesch J.B., Montminy M.; RT "TORCs: transducers of regulated CREB activity."; RL Mol. Cell 12:413-423(2003). RN [6] RP INTERACTION WITH CREB1; SIK2; PPP3CA; YWHAB AND YWHAG, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, FUNCTION, PHOSPHORYLATION AT SER-70; SER-90; SER-136; RP SER-171; SER-306; SER-368; SER-393; SER-433; SER-456; SER-489; SER-492 AND RP SER-613, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-171 RP AND SER-368. 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 [7] RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=15589160; DOI=10.1016/j.cub.2004.11.002; RA Bittinger M.A., McWhinnie E., Meltzer J., Iourgenko V., Latario B., Liu X., RA Chen C.H., Song C., Garza D., Labow M.; RT "Activation of cAMP response element-mediated gene expression by regulated RT nuclear transport of TORC proteins."; RL Curr. Biol. 14:2156-2161(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-171, AND MUTAGENESIS RP OF SER-171. 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 [9] RP INTERACTION WITH HTLV-1 TAX (MICROBIAL INFECTION), AND FUNCTION. RX PubMed=16809310; DOI=10.1128/jvi.00103-06; RA Siu Y.-T., Chin K.-T., Siu K.-L., Yee Wai Choy E., Jeang K.-T., Jin D.-Y.; RT "TORC1 and TORC2 coactivators are required for tax activation of the human RT T-cell leukemia virus type 1 long terminal repeats."; RL J. Virol. 80:7052-7059(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [11] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=16980408; DOI=10.1073/pnas.0606714103; RA Wu Z., Huang X., Feng Y., Handschin C., Feng Y., Gullicksen P.S., Bare O., RA Labow M., Spiegelman B., Stevenson S.C.; RT "Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha RT transcription and mitochondrial biogenesis in muscle cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:14379-14384(2006). RN [12] RP FUNCTION, AND PHOSPHORYLATION AT SER-171. RX PubMed=17210223; DOI=10.1016/j.mce.2006.12.020; RA Takemori H., Kanematsu M., Kajimura J., Hatano O., Katoh Y., Lin X.-Z., RA Min L., Yamazaki T., Doi J., Okamoto M.; RT "Dephosphorylation of TORC initiates expression of the StAR gene."; RL Mol. Cell. Endocrinol. 265:196-204(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [14] RP PHOSPHORYLATION AT SER-171 AND SER-274, INTERACTION WITH 14-3-3, AND RP MUTAGENESIS OF SER-171; SER-274 AND SER-368. RX PubMed=18626018; DOI=10.1073/pnas.0800796105; RA Jansson D., Ng A.C., Fu A., Depatie C., Al Azzabi M., Screaton R.A.; RT "Glucose controls CREB activity in islet cells via regulated RT phosphorylation of TORC2."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10161-10166(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-86; SER-90; SER-136; RP SER-433; THR-501; SER-613 AND SER-624, AND IDENTIFICATION BY MASS RP 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 [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-86; SER-90; THR-192; RP SER-433; TYR-488; SER-490; SER-613 AND SER-624, AND IDENTIFICATION BY MASS RP 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-501; SER-613 AND SER-624, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433; SER-613 AND SER-624, AND RP IDENTIFICATION BY 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 [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90 AND SER-613, AND RP IDENTIFICATION BY 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 [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-234, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [25] RP INTERACTION WITH YWHAE AND PPP3CA. 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). RN [26] RP VARIANT CYS-379, AND INVOLVEMENT IN SUSCEPTIBILITY TO NIDDM. RX PubMed=17950019; DOI=10.1016/j.ymgme.2007.08.125; RA Keshavarz P., Inoue H., Nakamura N., Yoshikawa T., Tanahashi T., RA Itakura M.; RT "Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 RT (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes."; RL Mol. Genet. Metab. 93:200-209(2008). CC -!- FUNCTION: Transcriptional coactivator for CREB1 which activates CC transcription through both consensus and variant cAMP response element CC (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, CC being active when dephosphorylated and acts independently of CREB1 CC 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. CC Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 CC signaling pathway. Regulates the expression of specific genes such as CC the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and CC inducer of mitochondrial biogenesis in muscle cells. Also coactivator CC for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) CC long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, CC ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081, CC ECO:0000269|PubMed:16809310, ECO:0000269|PubMed:16817901, CC ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223}. CC -!- SUBUNIT: Binds, as a tetramer, through its N-terminal region, with the CC bZIP domain of CREB1 (PubMed:15454081). 'Arg-314' in the bZIP domain of CC CREB1 is essential for this interaction (PubMed:15454081). Interaction, CC via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1 CC (PubMed:15454081). Interacts with SIK2 (PubMed:15454081). Interacts CC with 14-3-3 proteins, YWHAB and YWHAG (PubMed:15454081, CC PubMed:18626018). Interacts (probably when phosphorylated at Ser-171) CC with YWHAE (PubMed:30611118). Interacts with calmodulin-dependent CC catalytic subunit PPP3CA/calcineurin A (PubMed:15454081, CC PubMed:30611118). Interaction with COP1 mediates nuclear export and CC degradation of CRTC2 (By similarity). {ECO:0000250|UniProtKB:Q3U182, CC ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:18626018, CC ECO:0000269|PubMed:30611118}. CC -!- SUBUNIT: (Microbial infection) Interaction with the human T-cell CC leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal CC transcription activation by Tax. {ECO:0000269|PubMed:16809310}. CC -!- INTERACTION: CC Q53ET0; P18850: ATF6; NbExp=3; IntAct=EBI-1181987, EBI-852157; CC Q53ET0; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-1181987, EBI-1166928; CC Q53ET0; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-1181987, EBI-10961624; CC Q53ET0; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-1181987, EBI-396137; CC Q53ET0; P16220: CREB1; NbExp=3; IntAct=EBI-1181987, EBI-711855; CC Q53ET0; Q15233: NONO; NbExp=2; IntAct=EBI-1181987, EBI-350527; CC Q53ET0; Q9UMX1: SUFU; NbExp=5; IntAct=EBI-1181987, EBI-740595; CC Q53ET0; P31946: YWHAB; NbExp=4; IntAct=EBI-1181987, EBI-359815; CC Q53ET0; P03206: BZLF1; Xeno; NbExp=3; IntAct=EBI-1181987, EBI-2621186; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15589160}. Nucleus CC {ECO:0000269|PubMed:15589160}. Note=Translocated from the nucleus to CC the cytoplasm on interaction of the phosphorylated form with 14-3-3 CC protein (PubMed:15454081). In response to cAMP levels and glucagon, CC relocated to the nucleus (PubMed:15454081). CC {ECO:0000269|PubMed:15454081}. CC -!- TISSUE SPECIFICITY: Most abundantly expressed in the thymus. Present in CC both B and T-lymphocytes. Highly expressed in HEK293T cells and in CC insulinomas. High levels also in spleen, ovary, muscle and lung, with CC highest levels in muscle. Lower levels found in brain, colon, heart, CC kidney, prostate, small intestine and stomach. Weak expression in liver CC and pancreas. {ECO:0000269|PubMed:14536081, CC ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:16980408}. CC -!- PTM: Phosphorylation/dephosphorylation states of Ser-171 are required CC for regulating transduction of CREB activity (PubMed:15589160, CC PubMed:17210223). CRTCs/TORCs are inactive when phosphorylated, and CC active when dephosphorylated at this site (PubMed:17210223). This CC primary site of phosphorylation, is regulated by cAMP and calcium CC levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2) CC by LKB1 (PubMed:15454081, PubMed:16817901). Following adenylyl cyclase CC activation, dephosphorylated at Ser-171 by PPP3CA/calcineurin A CC resulting in CRTC2 dissociation from 14-3-3 proteins and PPP3CA (By CC similarity). Both insulin and AMPK increase this phosphorylation of CC CRTC2 while glucagon suppresses it (PubMed:15454081). Phosphorylation CC at Ser-274 by MARK2 is induced under low glucose conditions and CC dephosphorylated in response to glucose influx (PubMed:18626018). CC Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins CC and translocation to the cytoplasm (PubMed:18626018). CC {ECO:0000250|UniProtKB:Q3U182, ECO:0000269|PubMed:15454081, CC ECO:0000269|PubMed:15589160, ECO:0000269|PubMed:16817901, CC ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:18626018}. 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:0000250|UniProtKB:Q3U182}. CC -!- POLYMORPHISM: Variant Cys-379, under a dominant model, linked to a CC recessive mutation in LKB1, may be associated with susceptibility to CC type II or non-insulin-dependent diabetes mellitus (NIDDM). CC {ECO:0000269|PubMed:17950019}. CC -!- SIMILARITY: Belongs to the TORC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/50581/CRTC2"; 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; AY360172; AAQ98857.1; -; mRNA. DR EMBL; AK223559; BAD97279.1; -; mRNA. DR EMBL; AL358472; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC028886; AAH28886.1; -; mRNA. DR EMBL; BC053562; AAH53562.1; -; mRNA. DR CCDS; CCDS30875.1; -. DR RefSeq; NP_859066.1; NM_181715.2. DR PDB; 4HTM; X-ray; 2.00 A; A=18-50. DR PDBsum; 4HTM; -. DR AlphaFoldDB; Q53ET0; -. DR SMR; Q53ET0; -. DR BioGRID; 128308; 63. DR DIP; DIP-29950N; -. DR IntAct; Q53ET0; 29. DR MINT; Q53ET0; -. DR STRING; 9606.ENSP00000357622; -. DR GlyCosmos; Q53ET0; 10 sites, 2 glycans. DR GlyGen; Q53ET0; 11 sites, 2 O-linked glycans (11 sites). DR iPTMnet; Q53ET0; -. DR PhosphoSitePlus; Q53ET0; -. DR BioMuta; CRTC2; -. DR DMDM; 167009135; -. DR EPD; Q53ET0; -. DR jPOST; Q53ET0; -. DR MassIVE; Q53ET0; -. DR MaxQB; Q53ET0; -. DR PaxDb; 9606-ENSP00000357622; -. DR PeptideAtlas; Q53ET0; -. DR ProteomicsDB; 62448; -. DR Pumba; Q53ET0; -. DR Antibodypedia; 34141; 673 antibodies from 40 providers. DR DNASU; 200186; -. DR Ensembl; ENST00000368633.2; ENSP00000357622.1; ENSG00000160741.17. DR GeneID; 200186; -. DR KEGG; hsa:200186; -. DR MANE-Select; ENST00000368633.2; ENSP00000357622.1; NM_181715.3; NP_859066.1. DR UCSC; uc057leo.1; human. DR AGR; HGNC:27301; -. DR CTD; 200186; -. DR DisGeNET; 200186; -. DR GeneCards; CRTC2; -. DR HGNC; HGNC:27301; CRTC2. DR HPA; ENSG00000160741; Low tissue specificity. DR MIM; 608972; gene. DR neXtProt; NX_Q53ET0; -. DR OpenTargets; ENSG00000160741; -. DR PharmGKB; PA142672073; -. DR VEuPathDB; HostDB:ENSG00000160741; -. DR eggNOG; ENOG502QVWA; Eukaryota. DR GeneTree; ENSGT00390000010652; -. DR InParanoid; Q53ET0; -. DR OMA; YPRHIID; -. DR OrthoDB; 2906223at2759; -. DR PhylomeDB; Q53ET0; -. DR TreeFam; TF321571; -. DR PathwayCommons; Q53ET0; -. DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis. DR Reactome; R-HSA-400253; Circadian Clock. DR Reactome; R-HSA-9707616; Heme signaling. DR SignaLink; Q53ET0; -. DR SIGNOR; Q53ET0; -. DR BioGRID-ORCS; 200186; 35 hits in 1168 CRISPR screens. DR ChiTaRS; CRTC2; human. DR GeneWiki; CRTC2; -. DR GenomeRNAi; 200186; -. DR Pharos; Q53ET0; Tbio. DR PRO; PR:Q53ET0; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q53ET0; Protein. DR Bgee; ENSG00000160741; Expressed in granulocyte and 142 other cell types or tissues. DR ExpressionAtlas; Q53ET0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0008140; F:cAMP response element binding protein binding; IBA:GO_Central. DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro. DR InterPro; IPR024786; TORC. DR InterPro; IPR024785; TORC_C. DR InterPro; IPR024784; TORC_M. DR InterPro; IPR024783; TORC_N. DR PANTHER; PTHR13589; CREB-REGULATED TRANSCRIPTION COACTIVATOR; 1. DR PANTHER; PTHR13589:SF6; CREB-REGULATED TRANSCRIPTION COACTIVATOR 2; 1. DR Pfam; PF12886; TORC_C; 1. DR Pfam; PF12885; TORC_M; 1. DR Pfam; PF12884; TORC_N; 1. DR Genevisible; Q53ET0; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Cytoplasm; Host-virus interaction; KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..693 FT /note="CREB-regulated transcription coactivator 2" FT /id="PRO_0000318528" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 282..306 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 328..554 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 271..287 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 338..414 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 447..486 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 493..527 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 629 FT /note="Required for ubiquitination and degradation" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 51 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332" FT MOD_RES 86 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 90 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:24275569" FT MOD_RES 99 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 120 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 123 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 136 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0007744|PubMed:18669648" FT MOD_RES 161 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 168 FT /note="Asymmetric dimethylarginine; by PRMT6" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 169 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 171 FT /note="Phosphoserine; by AMPK, MARK2, SIK1 and SIK2" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:17210223, FT ECO:0000269|PubMed:18626018" FT MOD_RES 192 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 274 FT /note="Phosphoserine; by MARK2" FT /evidence="ECO:0000269|PubMed:18626018" FT MOD_RES 306 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 368 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 433 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 488 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 489 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 490 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 492 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081" FT MOD_RES 501 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 613 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 623 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U182" FT MOD_RES 624 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 234 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 147 FT /note="M -> V (in dbSNP:rs11264680)" FT /id="VAR_038756" FT VARIANT 379 FT /note="R -> C (in dbSNP:rs150423770)" FT /evidence="ECO:0000269|PubMed:14506290, FT ECO:0000269|PubMed:17950019" FT /id="VAR_038757" FT MUTAGEN 70 FT /note="S->A: No effect on cAMP- and calcium-regulated FT phosphorylation." FT MUTAGEN 171 FT /note="S->A: Loss of cAMP- and calcium-regulated FT phosphorylation. Greatly reduced interaction with 14-3-3 FT proteins. Impaired phosphorylation under low glucose FT conditions and impaired interaction with 14-3-3 proteins; FT when associated with A-274." FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:18626018" FT MUTAGEN 274 FT /note="S->A: Impaired phosphorylation under low glucose FT conditions and impaired interaction with 14-3-3 proteins; FT when associated with A-171." FT /evidence="ECO:0000269|PubMed:18626018" FT MUTAGEN 368 FT /note="S->A: Reduced cAMP- and calcium-regulated FT phosphorylation." FT /evidence="ECO:0000269|PubMed:15454081, FT ECO:0000269|PubMed:18626018" FT MUTAGEN 393 FT /note="S->A: No effect on cAMP- and calcium-regulated FT phosphorylation." FT CONFLICT 323..325 FT /note="MGL -> HGP (in Ref. 1; AAQ98857)" FT /evidence="ECO:0000305" FT CONFLICT 499 FT /note="P -> S (in Ref. 2; BAD97279)" FT /evidence="ECO:0000305" FT HELIX 21..45 FT /evidence="ECO:0007829|PDB:4HTM" SQ SEQUENCE 693 AA; 73302 MW; EE6C52E0ECDC1DF1 CRC64; MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST RLQAQKLRLA YTRSSHYGGS LPNVNQIGSG LAEFQSPLHS PLDSSRSTRH HGLVERVQRD PRRMVSPLRR YTRHIDSSPY SPAYLSPPPE SSWRRTMAWG NFPAEKGQLF RLPSALNRTS SDSALHTSVM NPSPQDTYPG PTPPSILPSR RGGILDGEMD PKVPAIEENL LDDKHLLKPW DAKKLSSSSS RPRSCEVPGI NIFPSPDQPA NVPVLPPAMN TGGSLPDLTN LHFPPPLPTP LDPEETAYPS LSGGNSTSNL THTMTHLGIS RGMGLGPGYD APGLHSPLSH PSLQSSLSNP NLQASLSSPQ PQLQGSHSHP SLPASSLARH VLPTTSLGHP SLSAPALSSS SSSSSTSSPV LGAPSYPAST PGASPHHRRV PLSPLSLLAG PADARRSQQQ LPKQFSPTMS PTLSSITQGV PLDTSKLSTD QRLPPYPYSS PSLVLPTQPH TPKSLQQPGL PSQSCSVQSS GGQPPGRQSH YGTPYPPGPS GHGQQSYHRP MSDFNLGNLE QFSMESPSAS LVLDPPGFSE GPGFLGGEGP MGGPQDPHTF NHQNLTHCSR HGSGPNIILT GDSSPGFSKE IAAALAGVPG FEVSAAGLEL GLGLEDELRM EPLGLEGLNM LSDPCALLPD PAVEESFRSD RLQ //