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Protein

CREB-regulated transcription coactivator 2

Gene

Crtc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei628Required for ubiquitination and degradation1

GO - Molecular functioni

GO - Biological processi

  • gluconeogenesis Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • histone H3-K9 acetylation Source: MGI
  • positive regulation of CREB transcription factor activity Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein homotetramerization Source: InterPro
  • toxin transport Source: MGI
  • 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
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1921593. Crtc2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi171S → A: Upregulates CREB-mediated gluconeogenic gene expression. No degradation of CRTC2. Loss of SIK2-mediated phosphorylation. 1 Publication1
Mutagenesisi213K → R: No effect on COP1-mediated degradation of TORC1 under forksolin stimulation. 1
Mutagenesisi214V → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication1
Mutagenesisi215P → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication1
Mutagenesisi628K → R: Translocates to the nucleus and no COP1-mediated degradation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003185292 – 692CREB-regulated transcription coactivator 2Add BLAST691

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei51Asymmetric dimethylarginine; by PRMT61 Publication1
Modified residuei70PhosphoserineCombined sources1
Modified residuei86PhosphoserineBy similarity1
Modified residuei90PhosphoserineBy similarity1
Modified residuei99Asymmetric dimethylarginine; by PRMT61 Publication1
Modified residuei120Asymmetric dimethylarginine; by PRMT61 Publication1
Modified residuei123Asymmetric dimethylarginine; by PRMT61 Publication1
Modified residuei136PhosphoserineBy similarity1
Modified residuei161Asymmetric dimethylarginine; by PRMT6Combined sources1 Publication1
Modified residuei168Asymmetric dimethylarginine; by PRMT61 Publication1
Modified residuei171Phosphoserine; by AMPK, MARK2, SIK1 and SIK2Combined sources3 Publications1
Modified residuei192PhosphothreonineBy similarity1
Modified residuei275Phosphoserine; by MARK2By similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei369PhosphoserineBy similarity1
Modified residuei394PhosphoserineBy similarity1
Modified residuei434PhosphoserineCombined sources1
Modified residuei457PhosphoserineBy similarity1
Modified residuei489PhosphotyrosineBy similarity1
Modified residuei490PhosphoserineBy similarity1
Modified residuei493PhosphoserineBy similarity1
Modified residuei502PhosphothreonineBy similarity1
Modified residuei612PhosphoserineCombined sources1
Modified residuei622PhosphoserineCombined sources1
Modified residuei623PhosphoserineCombined sources1

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

EPDiQ3U182.
MaxQBiQ3U182.
PaxDbiQ3U182.
PeptideAtlasiQ3U182.
PRIDEiQ3U182.

PTM databases

iPTMnetiQ3U182.
PhosphoSitePlusiQ3U182.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000027936.
CleanExiMM_CRTC2.
ExpressionAtlasiQ3U182. baseline and differential.
GenevisibleiQ3U182. MM.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216678. 4 interactors.
DIPiDIP-46162N.
IntActiQ3U182. 1 interactor.
STRINGi10090.ENSMUSP00000029545.

Structurei

3D structure databases

ProteinModelPortaliQ3U182.
SMRiQ3U182.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni209 – 215Required for interaction with RFWD2/COP11 Publication7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi272 – 288Nuclear export signalBy similarityAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi237 – 241Poly-Ser5
Compositional biasi337 – 413Ser-richAdd BLAST77

Sequence similaritiesi

Belongs to the TORC family.Curated

Phylogenomic databases

eggNOGiENOG410IGNT. Eukaryota.
ENOG410XPDQ. LUCA.
GeneTreeiENSGT00390000010652.
HOGENOMiHOG000111980.
HOVERGENiHBG058314.
InParanoidiQ3U182.
KOiK16333.
OMAiHTLNHQN.
OrthoDBiEOG091G03YN.
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)DescriptionActionsGraphical viewLength
Sequence conflicti195S → G in BAE33618 (PubMed:16141072).Curated1
Sequence conflicti203G → R in BAE42818 (PubMed:16141072).Curated1

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.
CCDSiCCDS38501.1.
RefSeqiNP_083157.1. NM_028881.2.
UniGeneiMm.35627.

3D structure databases

ProteinModelPortaliQ3U182.
SMRiQ3U182.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216678. 4 interactors.
DIPiDIP-46162N.
IntActiQ3U182. 1 interactor.
STRINGi10090.ENSMUSP00000029545.

PTM databases

iPTMnetiQ3U182.
PhosphoSitePlusiQ3U182.

Proteomic databases

EPDiQ3U182.
MaxQBiQ3U182.
PaxDbiQ3U182.
PeptideAtlasiQ3U182.
PRIDEiQ3U182.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi200186.
MGIiMGI:1921593. Crtc2.

Phylogenomic databases

eggNOGiENOG410IGNT. Eukaryota.
ENOG410XPDQ. LUCA.
GeneTreeiENSGT00390000010652.
HOGENOMiHOG000111980.
HOVERGENiHBG058314.
InParanoidiQ3U182.
KOiK16333.
OMAiHTLNHQN.
OrthoDBiEOG091G03YN.
PhylomeDBiQ3U182.
TreeFamiTF321571.

Miscellaneous databases

PROiQ3U182.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027936.
CleanExiMM_CRTC2.
ExpressionAtlasiQ3U182. baseline and differential.
GenevisibleiQ3U182. MM.

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]
ProtoNetiSearch...

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 2, 2016
This is version 94 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.