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Protein

CREB-regulated transcription coactivator 2

Gene

Crtc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 by RNA polymerase II Source: MGI
  • protein homotetramerization Source: InterPro
  • toxin transport Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator
Biological processTranscription, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1921593 Crtc2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi171S → A: Upregulates CREB transcription factor activity. Reduces interaction with 14-3-3 proteins. 1 Publication1
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 COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication1
Mutagenesisi215P → A: No interaction with COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication1
Mutagenesisi275S → A: Does not affect interaction with 14-3-3 proteins. 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 Publication1
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 residuei169Phosphothreonine1 Publication1
Modified residuei171Phosphoserine; by AMPK, MARK2, SIK1 and SIK2Combined sources4 Publications1
Modified residuei192PhosphothreonineBy similarity1
Cross-linki235Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
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, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

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, and SIK2 (By similarity). Interacts with 14-3-3 proteins, YWHAB and YWHAG (PubMed:28235073). Interaction with COP1 mediates nuclear export and degradation of CRTC2 (PubMed:17805301).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216678, 4 interactors
DIPiDIP-46162N
ELMiQ3U182
IntActiQ3U182, 11 interactors
STRINGi10090.ENSMUSP00000029545

Structurei

3D structure databases

ProteinModelPortaliQ3U182
SMRiQ3U182
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni209 – 215Required for interaction with 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

InterProiView protein in InterPro
IPR024786 TORC
IPR024785 TORC_C
IPR024784 TORC_M
IPR024783 TORC_N
PANTHERiPTHR13589 PTHR13589, 1 hit
PfamiView protein in Pfam
PF12886 TORC_C, 1 hit
PF12885 TORC_M, 1 hit
PF12884 TORC_N, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiCRTC2_MOUSE
AccessioniPrimary (citable) accession number: Q3U182
Secondary accession number(s): Q3TA52, Q8BH09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: July 18, 2018
This is version 105 of the entry and version 2 of the sequence. See 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

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