CRTC2_HUMAN
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 03-AUG-2022, entry version 135.
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; 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="http://atlasgeneticsoncology.org/Genes/CRTC2ID50581ch1q21.html";
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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; 54.
DR DIP; DIP-29950N; -.
DR IntAct; Q53ET0; 31.
DR MINT; Q53ET0; -.
DR STRING; 9606.ENSP00000357622; -.
DR GlyGen; Q53ET0; 10 sites, 2 O-linked glycans (10 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; Q53ET0; -.
DR PeptideAtlas; Q53ET0; -.
DR PRIDE; Q53ET0; -.
DR ProteomicsDB; 62448; -.
DR Antibodypedia; 34141; 572 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 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; 1118500at2759; -.
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; 32 hits in 1085 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 140 other tissues.
DR ExpressionAtlas; Q53ET0; baseline and differential.
DR Genevisible; Q53ET0; HS.
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:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:Ensembl.
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 GO; GO:1901998; P:toxin transport; IEA:Ensembl.
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; 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
