UniProtKB - Q3U182 (CRTC2_MOUSE)
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Protein
CREB-regulated transcription coactivator 2
Gene
Crtc2
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 628 | Required for ubiquitination and degradation | 1 |
GO - Molecular functioni
- cAMP response element binding protein binding Source: GO_Central
- chromatin binding Source: Ensembl
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
Keywordsi
| Molecular function | Activator |
| Biological process | Transcription, Transcription regulation |
Names & Taxonomyi
| Protein namesi | Recommended name: CREB-regulated transcription coactivator 2Alternative 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 |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI:1921593. Crtc2. |
Subcellular locationi
GO - Cellular componenti
- cytoplasm Source: UniProtKB
- extracellular exosome Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 171 | S → A: Upregulates CREB-mediated gluconeogenic gene expression. No degradation of CRTC2. Loss of SIK2-mediated phosphorylation. 1 Publication | 1 | |
| Mutagenesisi | 213 | K → R: No effect on COP1-mediated degradation of TORC1 under forksolin stimulation. | 1 | |
| Mutagenesisi | 214 | V → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication | 1 | |
| Mutagenesisi | 215 | P → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication | 1 | |
| Mutagenesisi | 628 | K → R: Translocates to the nucleus and no COP1-mediated degradation. 1 Publication | 1 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Initiator methioninei | RemovedBy similarity | |||
| ChainiPRO_0000318529 | 2 – 692 | CREB-regulated transcription coactivator 2Add BLAST | 691 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
| Modified residuei | 51 | Asymmetric dimethylarginine; by PRMT61 Publication | 1 | |
| Modified residuei | 70 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 86 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 90 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 99 | Asymmetric dimethylarginine; by PRMT61 Publication | 1 | |
| Modified residuei | 120 | Asymmetric dimethylarginine; by PRMT61 Publication | 1 | |
| Modified residuei | 123 | Asymmetric dimethylarginine; by PRMT61 Publication | 1 | |
| Modified residuei | 136 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 161 | Asymmetric dimethylarginine; by PRMT6Combined sources1 Publication | 1 | |
| Modified residuei | 168 | Asymmetric dimethylarginine; by PRMT61 Publication | 1 | |
| Modified residuei | 171 | Phosphoserine; by AMPK, MARK2, SIK1 and SIK2Combined sources3 Publications | 1 | |
| Modified residuei | 192 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 275 | Phosphoserine; by MARK2By similarity | 1 | |
| Modified residuei | 307 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 369 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 394 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 434 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 457 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 489 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 490 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 493 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 502 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 612 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 622 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 623 | PhosphoserineCombined sources | 1 |
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, PhosphoproteinProteomic databases
| EPDi | Q3U182. |
| MaxQBi | Q3U182. |
| PaxDbi | Q3U182. |
| PeptideAtlasi | Q3U182. |
| PRIDEi | Q3U182. |
PTM databases
| iPTMneti | Q3U182. |
| PhosphoSitePlusi | Q3U182. |
Expressioni
Tissue specificityi
Expressed in the suprachiasmatic nucleus (SCN) of the brain.1 Publication
Gene expression databases
| Bgeei | ENSMUSG00000027936. |
| CleanExi | MM_CRTC2. |
| ExpressionAtlasi | Q3U182. baseline and differential. |
| Genevisiblei | Q3U182. 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
- cAMP response element binding protein binding Source: GO_Central
Protein-protein interaction databases
| BioGridi | 216678. 4 interactors. |
| DIPi | DIP-46162N. |
| IntActi | Q3U182. 1 interactor. |
| STRINGi | 10090.ENSMUSP00000029545. |
Structurei
3D structure databases
| ProteinModelPortali | Q3U182. |
| SMRi | Q3U182. |
| ModBasei | Search... |
| MobiDBi | Search... |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 209 – 215 | Required for interaction with RFWD2/COP11 Publication | 7 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 272 – 288 | Nuclear export signalBy similarityAdd BLAST | 17 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 237 – 241 | Poly-Ser | 5 | |
| Compositional biasi | 337 – 413 | Ser-richAdd BLAST | 77 |
Sequence similaritiesi
Belongs to the TORC family.Curated
Phylogenomic databases
| eggNOGi | ENOG410IGNT. Eukaryota. ENOG410XPDQ. LUCA. |
| GeneTreei | ENSGT00390000010652. |
| HOGENOMi | HOG000111980. |
| HOVERGENi | HBG058314. |
| InParanoidi | Q3U182. |
| KOi | K16333. |
| OMAi | WRRTMPW. |
| OrthoDBi | EOG091G03YN. |
| PhylomeDBi | Q3U182. |
| TreeFami | TF321571. |
Family and domain databases
| InterProi | View protein in InterPro IPR024786. TORC. IPR024785. TORC_C. IPR024784. TORC_M. IPR024783. TORC_N. |
| PANTHERi | PTHR13589. PTHR13589. 1 hit. |
| Pfami | View 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
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
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 195 | S → G in BAE33618 (PubMed:16141072).Curated | 1 | |
| Sequence conflicti | 203 | G → R in BAE42818 (PubMed:16141072).Curated | 1 |
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. |
Genome annotation databases
| Ensembli | ENSMUST00000029545; ENSMUSP00000029545; ENSMUSG00000027936. |
| GeneIDi | 74343. |
| KEGGi | mmu:74343. |
| UCSCi | uc008qbt.2. mouse. |
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. |
Entry informationi
| Entry namei | CRTC2_MOUSE | |
| Accessioni | Q3U182Primary (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: | June 7, 2017 | |
| This is version 98 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families
