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CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3)

 CRTC3_MOUSE             Reviewed;         619 AA.
Q91X84;
05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
05-FEB-2008, sequence version 2.
05-DEC-2018, entry version 116.
RecName: Full=CREB-regulated transcription coactivator 3;
AltName: Full=Transducer of regulated cAMP response element-binding protein 3;
Short=TORC-3;
Short=Transducer of CREB protein 3;
Name=Crtc3; Synonyms=Torc3;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Lung;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
STRAIN=FVB/N; TISSUE=Liver;
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).
[3]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-370, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brown adipose tissue, Heart, Kidney, Lung, Spleen, and Testis;
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).
[4]
FUNCTION, AND PHOSPHORYLATION AT SER-273.
PubMed=29211348; DOI=10.1111/febs.14351;
Sonntag T., Vaughan J.M., Montminy M.;
"14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible
kinases (SIKs).";
FEBS J. 0:0-0(2017).
[5]
IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-62;
THR-160; SER-162 AND SER-273, MUTAGENESIS OF SER-162 AND SER-273, 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 (PubMed:29211348). Acts as a coactivator, in
the SIK/TORC signaling pathway, being active when dephosphorylated
(PubMed:29211348). Acts independently of CREB1 'Ser-133'
phosphorylation (By similarity). Enhances the interaction of CREB1
with TAF4 (By similarity). Regulates the expression of specific
CREB-activated genes such as the steroidogenic gene, StAR (By
similarity). Potent coactivator of PPARGC1A and inducer of
mitochondrial biogenesis in muscle cells (By similarity).
{ECO:0000250|UniProtKB:Q6UUV7, ECO:0000269|PubMed:29211348}.
-!- SUBUNIT: Binding, as a tetramer, through its N-terminal region,
with the bZIP domain of CREB1 enhances recruitment of TAF4 to the
promoter (By similarity). 'Arg-314' in the bZIP domain of CREB1 is
essential for this interaction (By similarity). Interacts with 14-
3-3 proteins (PubMed:28235073). {ECO:0000250|UniProtKB:Q6UUV7,
ECO:0000269|PubMed:28235073}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6UUV7}.
Cytoplasm {ECO:0000250|UniProtKB:Q6UUV7}. Note=Appears to be
mainly nuclear. {ECO:0000250|UniProtKB:Q6UUV7}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q91X84-1; Sequence=Displayed;
Name=2;
IsoId=Q91X84-2; Sequence=VSP_031221;
Note=No experimental confirmation available.;
-!- PTM: Phosphorylation/dephosphorylation states of Ser-273 are
required for regulating transduction of CREB activity
(PubMed:29211348). TORCs are inactive when phosphorylated, and
active when dephosphorylated at this site (PubMed:29211348).
{ECO:0000269|PubMed:29211348}.
-!- SIMILARITY: Belongs to the TORC family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AK144840; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; BC011210; AAH11210.1; -; mRNA.
CCDS; CCDS21398.2; -. [Q91X84-1]
RefSeq; NP_776288.2; NM_173863.2. [Q91X84-1]
RefSeq; XP_006541259.1; XM_006541196.1. [Q91X84-2]
UniGene; Mm.392175; -.
ProteinModelPortal; Q91X84; -.
SMR; Q91X84; -.
STRING; 10090.ENSMUSP00000113540; -.
iPTMnet; Q91X84; -.
PhosphoSitePlus; Q91X84; -.
PaxDb; Q91X84; -.
PeptideAtlas; Q91X84; -.
PRIDE; Q91X84; -.
Ensembl; ENSMUST00000122255; ENSMUSP00000113540; ENSMUSG00000030527. [Q91X84-1]
GeneID; 70461; -.
KEGG; mmu:70461; -.
UCSC; uc009iaz.1; mouse. [Q91X84-1]
CTD; 64784; -.
MGI; MGI:1917711; Crtc3.
eggNOG; ENOG410IGNT; Eukaryota.
eggNOG; ENOG410XPDQ; LUCA.
GeneTree; ENSGT00940000160398; -.
HOGENOM; HOG000111980; -.
HOVERGEN; HBG058314; -.
InParanoid; Q91X84; -.
KO; K16334; -.
OMA; RQFDGST; -.
OrthoDB; EOG091G03YN; -.
PhylomeDB; Q91X84; -.
TreeFam; TF321571; -.
ChiTaRS; Crtc3; mouse.
PRO; PR:Q91X84; -.
Proteomes; UP000000589; Chromosome 7.
Bgee; ENSMUSG00000030527; Expressed in 231 organ(s), highest expression level in gonadal ridge.
CleanEx; MM_CRTC3; -.
ExpressionAtlas; Q91X84; baseline and differential.
Genevisible; Q91X84; MM.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0008140; F:cAMP response element binding protein binding; IBA:GO_Central.
GO; GO:0097009; P:energy homeostasis; IMP:MGI.
GO; GO:0042116; P:macrophage activation; ISO:MGI.
GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:MGI.
GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:MGI.
GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IBA:GO_Central.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
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; Alternative splicing; Complete proteome; Cytoplasm;
Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
Transcription; Transcription regulation; Ubl conjugation.
CHAIN 1 619 CREB-regulated transcription coactivator
3.
/FTId=PRO_0000318532.
MOD_RES 4 4 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 62 62 Phosphoserine.
{ECO:0000244|PubMed:21183079,
ECO:0000269|PubMed:28235073}.
MOD_RES 160 160 Phosphothreonine.
{ECO:0000269|PubMed:28235073}.
MOD_RES 162 162 Phosphoserine; by SIK2.
{ECO:0000269|PubMed:28235073}.
MOD_RES 273 273 Phosphoserine.
{ECO:0000269|PubMed:28235073,
ECO:0000269|PubMed:29211348}.
MOD_RES 329 329 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 332 332 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 370 370 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 391 391 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 396 396 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 410 410 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
MOD_RES 443 443 Phosphoserine.
{ECO:0000250|UniProtKB:Q6UUV7}.
CROSSLNK 232 232 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q6UUV7}.
VAR_SEQ 1 299 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_031221.
MUTAGEN 162 162 S->A: Up-regulates CREB transcription
factor activity. Reduces interaction with
14-3-3 proteins.
{ECO:0000269|PubMed:28235073}.
MUTAGEN 273 273 S->A: Reduces interaction with 14-3-3
proteins. {ECO:0000269|PubMed:28235073}.
SEQUENCE 619 AA; 67027 MW; FBBE723F186CD60E CRC64;
MAASPGSGSA NPRKFSEKIA LHTQRQAEET RAFEQLMTDL TLSRVQFQKL QQLRLTQYHG
GSLPNVSQLR NSAPEFQPSL HQADNVRGTR HHGLVERPAR NRFHPLHRRS GDKPGRQFDG
NAFAASYSSQ HLDESWPRQQ PPWKEEKHPG FRLTSALNRT NSDSALHTSA LSTKPQDPYG
GGGQSAWPAP YMGFCDGEND GHAEVAAFPG PLKEENLLNV PKPLPKHLWE SKEIQSLSGR
PRSCDVGGGN AFPHNGQNTG LSPFLGTLNT GGSLPDLTNL HYSAPLPASL DTSDHLFGSM
SVGNSVGNLP AAMTHLGIRT SSGLQSSRSN PSIQATLSKM ALSSSLKCHP QPSVANASAL
HPSLRLFSLS NPSLSTTNLS GPSRRRQPPV SPLTLSPGPE AHQGFSRQLS ATSPLNPYPA
SQMVTSEQSP LSFLPTDAQA QVSPPPPYPT PQELPQPLLQ QPHAQEPPTQ QPQAAPSLPQ
SDFQLLTAQG SALTSFFPDV RFDQQPMRPS PAFPQQVPLV QQSHREPQDS FHLRPNPYSS
CGSFPGTILT EDTNSNLFKG LSGGLSGMPE VSLDMDTPFP LEEELQIEPL SLDGLNMLSD
SSMGLLDPSV EETFRADRL


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