CRTC1_MOUSE
ID CRTC1_MOUSE Reviewed; 630 AA.
AC Q68ED7; Q6ZQ85;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=CREB-regulated transcription coactivator 1;
DE AltName: Full=Mucoepidermoid carcinoma translocated protein 1 homolog;
DE AltName: Full=Transducer of regulated cAMP response element-binding protein 1;
DE Short=TORC-1;
DE Short=Transducer of CREB protein 1;
GN Name=Crtc1 {ECO:0000312|MGI:MGI:2142523};
GN Synonyms=Kiaa0616 {ECO:0000312|EMBL:BAC97983.1},
GN Mect1 {ECO:0000312|EMBL:AAH80308.1}, Torc1;
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] {ECO:0000312|EMBL:AAH80308.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH80308.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH80308.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2] {ECO:0000312|EMBL:BAC97983.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:BAC97983.1};
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17360587; DOI=10.1073/pnas.0607524104;
RA Kovacs K.A., Steullet P., Steinmann M., Do K.Q., Magistretti P.J.,
RA Halfon O., Cardinaux J.R.;
RT "TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in
RT hippocampal long-term synaptic plasticity.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4700-4705(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, and Spleen;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
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).
RN [6]
RP FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION.
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-64; THR-149 AND
RP SER-151, MUTAGENESIS OF SER-64; SER-151 AND SER-245, AND INTERACTION WITH
RP 14-3-3 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 [9]
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).
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 the expression of specific CREB-activated genes such as the
CC steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer
CC of mitochondrial biogenesis in muscle cells (By similarity). In the
CC hippocampus, involved in late-phase long-term potentiation (L-LTP)
CC maintenance at the Schaffer collateral-CA1 synapses. May be required
CC for dendritic growth of developing cortical neurons. In concert with
CC SIK1, regulates the light-induced entrainment of the circadian clock.
CC In response to light stimulus, coactivates the CREB-mediated
CC transcription of PER1 which plays an important role in the photic
CC entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1,
CC ECO:0000250|UniProtKB:Q6UUV9, ECO:0000269|PubMed:17360587,
CC ECO:0000269|PubMed:23699513, ECO:0000269|PubMed:23993098,
CC ECO:0000269|PubMed:29211348}.
CC -!- SUBUNIT: Binds, as a tetramer, through its N-terminal region, with the
CC bZIP domain of CREB1 (By similarity). 'Arg-314' in the bZIP domain of
CC CREB1 is essential for this interaction (By similarity). Interaction,
CC via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1
CC (By similarity). Interacts with 14-3-3 proteins, including YWHAE/14-3-3
CC epsilon (PubMed:28235073, PubMed:30611118). Interacts with calmodulin-
CC dependent catalytic subunit PPP3CA/calcineurin A (PubMed:30611118).
CC {ECO:0000250|UniProtKB:Q6UUV9, ECO:0000269|PubMed:28235073,
CC ECO:0000269|PubMed:30611118}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17360587,
CC ECO:0000269|PubMed:23993098}. Nucleus {ECO:0000269|PubMed:17360587,
CC ECO:0000269|PubMed:23699513, ECO:0000269|PubMed:23993098}.
CC Note=Cytoplasmic when phosphorylated by SIK or AMPK and when
CC sequestered by 14-3-3 proteins (By similarity). Translocated to the
CC nucleus on Ser-151 dephosphorylation, instigated by a number of factors
CC including calcium ion and cAMP levels (By similarity). Light
CC stimulation triggers a nuclear accumulation in the suprachiasmatic
CC nucleus (SCN) of the brain (PubMed:23699513).
CC {ECO:0000250|UniProtKB:Q6UUV9, ECO:0000269|PubMed:23699513}.
CC -!- TISSUE SPECIFICITY: Highly expressed in specific regions of the brain
CC including the cortex, hippocampus and striatum.
CC {ECO:0000269|PubMed:17360587}.
CC -!- INDUCTION: Expressed in a circadian manner in the suprachiasmatic
CC nucleus (SCN) of the brain. Expression is highest during the day and
CC reaches a nadir during the early subjective night.
CC {ECO:0000269|PubMed:23699513}.
CC -!- PTM: Phosphorylation/dephosphorylation states of Ser-151 are required
CC for regulating transduction of CREB activity. TORCs are inactive when
CC phosphorylated, and active when dephosphorylated at this site. This
CC primary site of phosphorylation is mediated by SIKs (SIK1 and SIK2), is
CC regulated by cAMP and calcium levels and is dependent on the
CC phosphorylation of SIKs by LKB1. {ECO:0000269|PubMed:23993098}.
CC -!- SIMILARITY: Belongs to the TORC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC97983.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC080308; AAH80308.1; -; mRNA.
DR EMBL; AK129173; BAC97983.1; ALT_INIT; mRNA.
DR CCDS; CCDS40372.1; -.
DR RefSeq; NP_001004062.1; NM_001004062.2.
DR AlphaFoldDB; Q68ED7; -.
DR SMR; Q68ED7; -.
DR BioGRID; 238211; 5.
DR STRING; 10090.ENSMUSP00000075916; -.
DR iPTMnet; Q68ED7; -.
DR PhosphoSitePlus; Q68ED7; -.
DR EPD; Q68ED7; -.
DR MaxQB; Q68ED7; -.
DR PaxDb; Q68ED7; -.
DR PeptideAtlas; Q68ED7; -.
DR PRIDE; Q68ED7; -.
DR ProteomicsDB; 283958; -.
DR Antibodypedia; 15141; 380 antibodies from 41 providers.
DR Ensembl; ENSMUST00000076615; ENSMUSP00000075916; ENSMUSG00000003575.
DR GeneID; 382056; -.
DR KEGG; mmu:382056; -.
DR UCSC; uc009mae.1; mouse.
DR CTD; 23373; -.
DR MGI; MGI:2142523; Crtc1.
DR VEuPathDB; HostDB:ENSMUSG00000003575; -.
DR eggNOG; ENOG502QU41; Eukaryota.
DR GeneTree; ENSGT00390000010652; -.
DR HOGENOM; CLU_019357_2_0_1; -.
DR InParanoid; Q68ED7; -.
DR OMA; FNMVEGA; -.
DR OrthoDB; 1118500at2759; -.
DR PhylomeDB; Q68ED7; -.
DR TreeFam; TF321571; -.
DR BioGRID-ORCS; 382056; 7 hits in 73 CRISPR screens.
DR PRO; PR:Q68ED7; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q68ED7; protein.
DR Bgee; ENSMUSG00000003575; Expressed in embryonic brain and 153 other tissues.
DR Genevisible; Q68ED7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008140; F:cAMP response element binding protein binding; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IMP:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0007613; P:memory; IMP:MGI.
DR GO; GO:1902631; P:negative regulation of membrane hyperpolarization; IDA:MGI.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IMP:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISO:MGI.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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 Activator; Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..630
FT /note="CREB-regulated transcription coactivator 1"
FT /id="PRO_0000096355"
FT REGION 140..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 257..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 242..258
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 142..174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 194..212
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..388
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 571
FT /note="Required for ubiquitination and degradation"
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28235073"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6UUV9"
FT MOD_RES 149
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:28235073"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28235073,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 161
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6UUV9"
FT MUTAGEN 64
FT /note="S->A: Up-regulates CREB transcription factor
FT activity."
FT /evidence="ECO:0000269|PubMed:28235073"
FT MUTAGEN 151
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 245
FT /note="S->A: No effect on interaction with 14-3-3
FT proteins."
FT /evidence="ECO:0000269|PubMed:28235073"
SQ SEQUENCE 630 AA; 66945 MW; FD0C37B48301471C CRC64;
MATSNNPRKF SEKIALHNQK QAEETAAFEE VMKDLSLTRA ARLQLQKSQY LQLGPSRGQY
YGGSLPNVNQ IGSSSVDLAF QTPFQSSGLD TSRTTRHHGL VDRVYRERGR LGSPHRRPLS
VDKHGRQADS CPYGTVYLSP PADTSWRRTN SDSALHQSTM TPSQAESFTG GSQDAHQKRV
LLLTVPGMED TGAETDKTLS KQSWDSKKAG SRPKSCEVPG INIFPSADQE NTTALIPATH
NTGGSLPDLT NIHFPSPLPT PLDPEEPPFP ALTSSSSTGS LAHLGVGGAG QGMNTPSSSP
QHRPAVVSPL SLSTEARRQQ AQQVSPTLSP LSPITQAVAM DALSLEQQLP YAFFTQTGSQ
QPPPQPQPPP PPPPVSQQQP PPPQVSVGLP QGGPLLPSAS LTRGPQLPPL SVTVPSTLPQ
SPTENPGQSP MGIDATSAPA LQYRTSAGSP ATQSPTSPVS NQGFSPGSSP QHTSTLGSVF
GDAYYEQQMT ARQANALSRQ LEQFNMMENA ISSSSLYNPG STLNYSQAAM MGLSGSHGGL
QDPQQLGYTG HGGIPNIILT VTGESPPSLS KELSSTLAGV SDVSFDSDHQ FPLDELKIDP
LTLDGLHMLN DPDMVLADPA TEDTFRMDRL
