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CREB-regulated transcription coactivator 1 (Mucoepidermoid carcinoma translocated protein 1 homolog) (Transducer of regulated cAMP response element-binding protein 1) (TORC-1) (Transducer of CREB protein 1)

 CRTC1_MOUSE             Reviewed;         630 AA.
Q68ED7; Q6ZQ85;
05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
11-OCT-2004, sequence version 1.
28-MAR-2018, entry version 99.
RecName: Full=CREB-regulated transcription coactivator 1;
AltName: Full=Mucoepidermoid carcinoma translocated protein 1 homolog;
AltName: Full=Transducer of regulated cAMP response element-binding protein 1;
Short=TORC-1;
Short=Transducer of CREB protein 1;
Name=Crtc1 {ECO:0000312|MGI:MGI:2142523};
Synonyms=Kiaa0616 {ECO:0000312|EMBL:BAC97983.1},
Mect1 {ECO:0000312|EMBL:AAH80308.1}, Torc1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1] {ECO:0000312|EMBL:AAH80308.1}
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH80308.1};
TISSUE=Brain {ECO:0000312|EMBL:AAH80308.1};
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[2] {ECO:0000312|EMBL:BAC97983.1}
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain {ECO:0000312|EMBL:BAC97983.1};
PubMed=14621295; DOI=10.1093/dnares/10.4.167;
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
Saga Y., Nagase T., Ohara O., Koga H.;
"Prediction of the coding sequences of mouse homologues of KIAA gene:
III. The complete nucleotide sequences of 500 mouse KIAA-homologous
cDNAs identified by screening of terminal sequences of cDNA clones
randomly sampled from size-fractionated libraries.";
DNA Res. 10:167-180(2003).
[3]
FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=17360587; DOI=10.1073/pnas.0607524104;
Kovacs K.A., Steullet P., Steinmann M., Do K.Q., Magistretti P.J.,
Halfon O., Cardinaux J.R.;
"TORC1 is a calcium- and cAMP-sensitive coincidence detector involved
in hippocampal long-term synaptic plasticity.";
Proc. Natl. Acad. Sci. U.S.A. 104:4700-4705(2007).
[4]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Kidney, Lung, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[5]
FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
PubMed=23993098; DOI=10.1016/j.cell.2013.08.004;
Jagannath A., Butler R., Godinho S.I., Couch Y., Brown L.A.,
Vasudevan S.R., Flanagan K.C., Anthony D., Churchill G.C., Wood M.J.,
Steiner G., Ebeling M., Hossbach M., Wettstein J.G., Duffield G.E.,
Gatti S., Hankins M.W., Foster R.G., Peirson S.N.;
"The CRTC1-SIK1 pathway regulates entrainment of the circadian
clock.";
Cell 154:1100-1111(2013).
[6]
FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=23699513; DOI=10.1523/JNEUROSCI.4202-12.2013;
Sakamoto K., Norona F.E., Alzate-Correa D., Scarberry D., Hoyt K.R.,
Obrietan K.;
"Clock and light regulation of the CREB coactivator CRTC1 in the
suprachiasmatic circadian clock.";
J. Neurosci. 33:9021-9027(2013).
[7]
IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-64;
THR-149 AND SER-151, MUTAGENESIS OF SER-64; SER-151 AND SER-245, AND
INTERACTION WITH 14-3-3 PROTEINS.
PubMed=28235073; DOI=10.1371/journal.pone.0173013;
Sonntag T., Moresco J.J., Vaughan J.M., Matsumura S., Yates J.R. III,
Montminy M.;
"Analysis of a cAMP regulated coactivator family reveals an
alternative phosphorylation motif for AMPK family members.";
PLoS ONE 12:E0173013-E0173013(2017).
-!- FUNCTION: Transcriptional coactivator for CREB1 which activates
transcription through both consensus and variant cAMP response
element (CRE) sites. Acts as a coactivator, in the SIK/TORC
signaling pathway, being active when dephosphorylated and acts
independently of CREB1 'Ser-133' phosphorylation. Enhances the
interaction of CREB1 with TAF4. Regulates the expression of
specific CREB-activated genes such as the steroidogenic gene,
StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial
biogenesis in muscle cells (By similarity). In the hippocampus,
involved in late-phase long-term potentiation (L-LTP) maintenance
at the Schaffer collateral-CA1 synapses. May be required for
dendritic growth of developing cortical neurons. In concert with
SIK1, regulates the light-induced entrainment of the circadian
clock. In response to light stimulus, coactivates the CREB-
mediated transcription of PER1 which plays an important role in
the photic entrainment of the circadian clock.
{ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q6UUV9,
ECO:0000269|PubMed:17360587, ECO:0000269|PubMed:23699513,
ECO:0000269|PubMed:23993098}.
-!- SUBUNIT: Binds, as a tetramer, through its N-terminal region, with
the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is
essential for this interaction. Interaction, via its C-terminal,
with TAF4, enhances recruitment of TAF4 to CREB1. Interacts with
14-3-3 proteins (PubMed:28235073). {ECO:0000250|UniProtKB:Q6UUV9,
ECO:0000269|PubMed:28235073}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17360587,
ECO:0000269|PubMed:23993098}. Nucleus
{ECO:0000269|PubMed:17360587, ECO:0000269|PubMed:23699513,
ECO:0000269|PubMed:23993098}. Note=Cytoplasmic when phosphorylated
by SIK or AMPK and when sequestered by 14-3-3 proteins (By
similarity). Translocated to the nucleus on Ser-151
dephosphorylation, instigated by a number of factors including
calcium ion and cAMP levels (By similarity). Light stimulation
triggers a nuclear accumulation in the suprachiasmatic nucleus
(SCN) of the brain (PubMed:23699513).
{ECO:0000250|UniProtKB:Q6UUV9, ECO:0000269|PubMed:23699513}.
-!- TISSUE SPECIFICITY: Highly expressed in specific regions of the
brain including the cortex, hippocampus and striatum.
{ECO:0000269|PubMed:17360587}.
-!- INDUCTION: Expressed in a circadian manner in the suprachiasmatic
nucleus (SCN) of the brain. Expression is highest during the day
and reaches a nadir during the early subjective night.
{ECO:0000269|PubMed:23699513}.
-!- PTM: Phosphorylation/dephosphorylation states of Ser-151 are
required for regulating transduction of CREB activity. TORCs are
inactive when phosphorylated, and active when dephosphorylated at
this site. This primary site of phosphorylation is mediated by
SIKs (SIK1 and SIK2), is regulated by cAMP and calcium levels and
is dependent on the phosphorylation of SIKs by LKB1.
{ECO:0000269|PubMed:23993098}.
-!- SIMILARITY: Belongs to the TORC family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BAC97983.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; BC080308; AAH80308.1; -; mRNA.
EMBL; AK129173; BAC97983.1; ALT_INIT; mRNA.
CCDS; CCDS40372.1; -.
RefSeq; NP_001004062.1; NM_001004062.2.
UniGene; Mm.227767; -.
ProteinModelPortal; Q68ED7; -.
SMR; Q68ED7; -.
BioGrid; 238211; 1.
STRING; 10090.ENSMUSP00000075916; -.
iPTMnet; Q68ED7; -.
PhosphoSitePlus; Q68ED7; -.
MaxQB; Q68ED7; -.
PaxDb; Q68ED7; -.
PeptideAtlas; Q68ED7; -.
PRIDE; Q68ED7; -.
Ensembl; ENSMUST00000076615; ENSMUSP00000075916; ENSMUSG00000003575.
GeneID; 382056; -.
KEGG; mmu:382056; -.
UCSC; uc009mae.1; mouse.
CTD; 23373; -.
MGI; MGI:2142523; Crtc1.
eggNOG; ENOG410IGNT; Eukaryota.
eggNOG; ENOG410XPDQ; LUCA.
GeneTree; ENSGT00390000010652; -.
HOGENOM; HOG000111980; -.
HOVERGEN; HBG058314; -.
InParanoid; Q68ED7; -.
KO; K15309; -.
OMA; PSMGIDI; -.
OrthoDB; EOG091G03YN; -.
PhylomeDB; Q68ED7; -.
TreeFam; TF321571; -.
PRO; PR:Q68ED7; -.
Proteomes; UP000000589; Chromosome 8.
Bgee; ENSMUSG00000003575; -.
CleanEx; MM_CRTC1; -.
Genevisible; Q68ED7; MM.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0030425; C:dendrite; IEA:Ensembl.
GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
GO; GO:0016604; C:nuclear body; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0045202; C:synapse; IEA:Ensembl.
GO; GO:0008140; F:cAMP response element binding protein binding; ISS:UniProtKB.
GO; GO:0097009; P:energy homeostasis; IMP:MGI.
GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
GO; GO:0007613; P:memory; IMP:MGI.
GO; GO:1902631; P:negative regulation of membrane hyperpolarization; IDA:MGI.
GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IMP:UniProtKB.
GO; GO:1900006; P:positive regulation of dendrite development; IEA:Ensembl.
GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
InterPro; IPR024786; TORC.
InterPro; IPR024785; TORC_C.
InterPro; IPR024784; TORC_M.
InterPro; IPR024783; TORC_N.
PANTHER; PTHR13589; PTHR13589; 1.
Pfam; PF12886; TORC_C; 1.
Pfam; PF12885; TORC_M; 1.
Pfam; PF12884; TORC_N; 1.
1: Evidence at protein level;
Activator; Biological rhythms; Complete proteome; Cytoplasm; Nucleus;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 630 CREB-regulated transcription coactivator
1.
/FTId=PRO_0000096355.
MOTIF 242 258 Nuclear export signal. {ECO:0000250}.
COMPBIAS 295 365 Ser-rich.
SITE 571 571 Required for ubiquitination and
degradation. {ECO:0000250}.
MOD_RES 64 64 Phosphoserine.
{ECO:0000269|PubMed:28235073}.
MOD_RES 113 113 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV9}.
MOD_RES 149 149 Phosphothreonine.
{ECO:0000269|PubMed:28235073}.
MOD_RES 151 151 Phosphoserine.
{ECO:0000244|PubMed:21183079,
ECO:0000269|PubMed:28235073}.
MOD_RES 161 161 Phosphothreonine.
{ECO:0000250|UniProtKB:Q6UUV9}.
MUTAGEN 64 64 S->A: Up-regulates CREB transcription
factor activity.
{ECO:0000269|PubMed:28235073}.
MUTAGEN 151 151 S->A: Up-regulates CREB transcription
factor activity. Reduces interaction with
14-3-3 proteins.
{ECO:0000269|PubMed:28235073}.
MUTAGEN 245 245 S->A: No effect on interaction with 14-3-
3 proteins.
{ECO:0000269|PubMed:28235073}.
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


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