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Q3U182

- CRTC2_MOUSE

UniProt

Q3U182 - CRTC2_MOUSE

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Protein

CREB-regulated transcription coactivator 2

Gene

Crtc2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei628 – 6281Required for ubiquitination and degradation

GO - Molecular functioni

  1. cAMP response element binding protein binding Source: InterPro

GO - Biological processi

  1. gluconeogenesis Source: UniProtKB
  2. glucose homeostasis Source: UniProtKB
  3. histone H3-K9 acetylation Source: MGI
  4. positive regulation of CREB transcription factor activity Source: UniProtKB
  5. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  6. protein homotetramerization Source: InterPro
  7. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
CREB-regulated transcription coactivator 2
Alternative name(s):
Transducer of regulated cAMP response element-binding protein 2
Short name:
TORC-2
Short name:
Transducer of CREB protein 2
Gene namesi
Name:Crtc2
Synonyms:Torc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:1921593. Crtc2.

Subcellular locationi

Cytoplasm. Nucleus
Note: Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein. In response to cAMP levels and glucagon, relocated to the nucleus.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular vesicular exosome Source: Ensembl
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi171 – 1711S → A: Upregulates CREB-mediated gluconeogenic gene expression. No degradation of CRTC2. Loss of SIK2-mediated phosphorylation. 1 Publication
Mutagenesisi213 – 2131K → R: No effect on COP1-mediated degradation of TORC1 under forksolin stimulation.
Mutagenesisi214 – 2141V → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication
Mutagenesisi215 – 2151P → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication
Mutagenesisi628 – 6281K → R: Translocates to the nucleus and no COP1-mediated degradation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 692691CREB-regulated transcription coactivator 2PRO_0000318529Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei51 – 511Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei70 – 701PhosphoserineBy similarity
Modified residuei86 – 861PhosphoserineBy similarity
Modified residuei90 – 901PhosphoserineBy similarity
Modified residuei99 – 991Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei120 – 1201Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei123 – 1231Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei136 – 1361PhosphoserineBy similarity
Modified residuei161 – 1611Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei168 – 1681Asymmetric dimethylarginine; by PRMT61 Publication
Modified residuei171 – 1711Phosphoserine; by AMPK, MARK2, SIK1 and SIK23 Publications
Modified residuei192 – 1921PhosphothreonineBy similarity
Modified residuei275 – 2751Phosphoserine; by MARK2By similarity
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei369 – 3691PhosphoserineBy similarity
Modified residuei394 – 3941PhosphoserineBy similarity
Modified residuei434 – 4341PhosphoserineBy similarity
Modified residuei457 – 4571PhosphoserineBy similarity
Modified residuei489 – 4891Phosphotyrosine
Modified residuei490 – 4901PhosphoserineBy similarity
Modified residuei493 – 4931PhosphoserineBy similarity
Modified residuei502 – 5021PhosphothreonineBy similarity
Modified residuei612 – 6121Phosphoserine1 Publication
Modified residuei623 – 6231PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation/dephosphorylation states of Ser-171 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 regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2) by LKB1. Phosphorylation at Ser-275 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx. Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it. Phosphorylation at Ser-275 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm (By similarity).By similarity
Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ3U182.
PaxDbiQ3U182.
PRIDEiQ3U182.

Expressioni

Tissue specificityi

Expressed in the suprachiasmatic nucleus (SCN) of the brain.1 Publication

Gene expression databases

BgeeiQ3U182.
CleanExiMM_CRTC2.
ExpressionAtlasiQ3U182. baseline and differential.
GenevestigatoriQ3U182.

Interactioni

Subunit structurei

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 (By similarity). Interacts with PPP3CA/calcineurin alpha, SIK2 and 14-3-3 proteins, YWHAB and YWHAG (By similarity). Interaction with RFWD2/COP1 mediates nuclear export and degradation of CRTC2.By similarity1 Publication

Protein-protein interaction databases

BioGridi216678. 3 interactions.
DIPiDIP-46162N.
IntActiQ3U182. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ3U182.
SMRiQ3U182. Positions 20-47.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni209 – 2157Required for interaction with RFWD2/COP1
Regioni272 – 28817Nuclear export signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi237 – 2415Poly-Ser
Compositional biasi337 – 41377Ser-richAdd
BLAST

Sequence similaritiesi

Belongs to the TORC family.Curated

Phylogenomic databases

eggNOGiNOG74259.
GeneTreeiENSGT00390000010652.
HOGENOMiHOG000111980.
HOVERGENiHBG058314.
InParanoidiQ3U182.
KOiK16333.
OMAiTHCSRHG.
OrthoDBiEOG7MKW5P.
PhylomeDBiQ3U182.
TreeFamiTF321571.

Family and domain databases

InterProiIPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view]
PANTHERiPTHR13589. PTHR13589. 1 hit.
PfamiPF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q3U182-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST
60 70 80 90 100
RLQAQKLRLA YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH
110 120 130 140 150
HGLVERVQRD ARRMVSPLRR YPRHIDSSPY SPAYLSPPPE SGWRRMMPWG
160 170 180 190 200
NLPAEKGQLF RLPSALNRTS SDSALHTSVM NPNPQDTYPG PTPPSVLPSR
210 220 230 240 250
RGGGFLDGEM DAKVPAIEEN VVDDKHLLKP WDAKKLSSSS SRPRSCEVPG
260 270 280 290 300
INIFPSPDQP ANVPVLPPAM NTGGSLPDLT NLHFPPPLPT PLDPEETVYP
310 320 330 340 350
SLSGGNSTTN LTHTMTHLGI SGGLGLGPSY DVPGLHSPLS HPSLQSSLSN
360 370 380 390 400
PNLQASLSSP QPQLQGSHSH PSLPASSLAH HALPTTSLGH PSLSAPALSS
410 420 430 440 450
SSSSSSTSSP VLSAPPYPAS TPGASPRHRR VPLSPLSLPA GPADARRSQQ
460 470 480 490 500
QLPKQFSPTM SPTLSSITQG VPLDTSKLPT DQRLPPYPYS PPSLVIPTHP
510 520 530 540 550
PTPKSLQQLP SQACLVQPSG GQPPGRQPHY GALYPPGSSG HGQQPYHRPI
560 570 580 590 600
NDFSLGNLEQ FNMESPSTSL VLDPPAFSEG PGFLGSEGSM SGPQDPHVLN
610 620 630 640 650
HQNLTHCSRH GSGPNIILTG DSSPGFSKEI AAALAGVPGF EVSASGLELG
660 670 680 690
LGLEDELRME PLGLEGLTML SDPCALLPDP AVEDSFRSDR LQ
Length:692
Mass (Da):73,216
Last modified:February 5, 2008 - v2
Checksum:i5BCBC416D45CFAD8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti195 – 1951S → G in BAE33618. (PubMed:16141072)Curated
Sequence conflicti203 – 2031G → R in BAE42818. (PubMed:16141072)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK156192 mRNA. Translation: BAE33618.1.
AK172084 mRNA. Translation: BAE42818.1.
BC023831 mRNA. Translation: AAH23831.1.
BC032183 mRNA. Translation: AAH32183.1.
BC033300 mRNA. Translation: AAH33300.1.
CCDSiCCDS38501.1.
RefSeqiNP_083157.1. NM_028881.2.
UniGeneiMm.35627.

Genome annotation databases

EnsembliENSMUST00000029545; ENSMUSP00000029545; ENSMUSG00000027936.
GeneIDi74343.
KEGGimmu:74343.
UCSCiuc008qbt.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK156192 mRNA. Translation: BAE33618.1 .
AK172084 mRNA. Translation: BAE42818.1 .
BC023831 mRNA. Translation: AAH23831.1 .
BC032183 mRNA. Translation: AAH32183.1 .
BC033300 mRNA. Translation: AAH33300.1 .
CCDSi CCDS38501.1.
RefSeqi NP_083157.1. NM_028881.2.
UniGenei Mm.35627.

3D structure databases

ProteinModelPortali Q3U182.
SMRi Q3U182. Positions 20-47.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 216678. 3 interactions.
DIPi DIP-46162N.
IntActi Q3U182. 1 interaction.

Proteomic databases

MaxQBi Q3U182.
PaxDbi Q3U182.
PRIDEi Q3U182.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000029545 ; ENSMUSP00000029545 ; ENSMUSG00000027936 .
GeneIDi 74343.
KEGGi mmu:74343.
UCSCi uc008qbt.2. mouse.

Organism-specific databases

CTDi 200186.
MGIi MGI:1921593. Crtc2.

Phylogenomic databases

eggNOGi NOG74259.
GeneTreei ENSGT00390000010652.
HOGENOMi HOG000111980.
HOVERGENi HBG058314.
InParanoidi Q3U182.
KOi K16333.
OMAi THCSRHG.
OrthoDBi EOG7MKW5P.
PhylomeDBi Q3U182.
TreeFami TF321571.

Miscellaneous databases

NextBioi 340497.
PROi Q3U182.
SOURCEi Search...

Gene expression databases

Bgeei Q3U182.
CleanExi MM_CRTC2.
ExpressionAtlasi Q3U182. baseline and differential.
Genevestigatori Q3U182.

Family and domain databases

InterProi IPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view ]
PANTHERi PTHR13589. PTHR13589. 1 hit.
Pfami PF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    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.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
    Tissue: Spleen.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver, Mammary tumor and Salivary gland.
  3. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-171, TISSUE SPECIFICITY.
  4. "The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin."
    Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N., Depinho R.A., Montminy M., Cantley L.C.
    Science 310:1642-1646(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT SER-171, SUBCELLULAR LOCATION.
  5. "Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2."
    Dentin R., Liu Y., Koo S.-H., Hedrick S., Vargas T., Heredia J., Yates J. III, Montminy M.
    Nature 449:366-369(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RFWD2, PHOSPHORYLATION AT SER-171, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-171; VAL-214; PRO-215 AND LYS-628.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Clock and light regulation of the CREB coactivator CRTC1 in the suprachiasmatic circadian clock."
    Sakamoto K., Norona F.E., Alzate-Correa D., Scarberry D., Hoyt K.R., Obrietan K.
    J. Neurosci. 33:9021-9027(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  9. "Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism."
    Han H.S., Jung C.Y., Yoon Y.S., Choi S., Choi D., Kang G., Park K.G., Kim S.T., Koo S.H.
    Sci. Signal. 7:RA19-RA19(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: METHYLATION AT ARG-51; ARG-99; ARG-120; ARG-123; ARG-161 AND ARG-168.

Entry informationi

Entry nameiCRTC2_MOUSE
AccessioniPrimary (citable) accession number: Q3U182
Secondary accession number(s): Q3TA52, Q8BH09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: November 26, 2014
This is version 76 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3