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CRTC2 (CREB regulated transcription coactivator 2)

Written2010-02Kristy A Brown, Nirukshi Samarageewa
Prince Henry's Institute, Clayton, Victoria, 3168, Australia

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)TORC2
Other aliasRP11-422P24.6
HGNC (Hugo) CRTC2
LocusID (NCBI) 200186
Atlas_Id 50581
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 153947672 and ends at 153958656 bp from pter ( according to hg19-Feb_2009)  [Mapping CRTC2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CRTC2 (1q21.3) / CREB3L4 (1q21.3)CRTC2 (1q21.3) / CRTC2 (1q21.3)CRTC2 (1q21.3) / LINC02210 (17q21.31)
GATAD2B (1q21.3) / CRTC2 (1q21.3)SLC39A1 (1q21.3) / CRTC2 (1q21.3)

DNA/RNA

Description 10,893 bases; on minus strand. Includes 14 exons.
Transcription Transcript measures 2598 bp with a 2082 bp coding sequence.

Protein

Description 693 amino acids; 73,302 Da.
Expression Particularly abundant in B and T lymphocytes. Higher levels were also seen in muscle, lung, spleen, ovary and breast. Lower expressions found in brain, colon, heart, kidney, prostate, small intestine and stomach, with significantly lowest expression in liver and pancreas.
Localisation Phosphorylation of CRTC2 triggers the phosphorylation-dependent binding to 14-3-3 proteins, and hence sequestration of CRTC2 in the cytosol thereby preventing its nuclear translocation and the activation of CREB. Proteins known to phosphorylate CRTC2 at Ser171 include AMP-activated protein kinase (AMPK) and the salt-inducible kinases (SIKs). Dephosphorylated CRTC2 readily translocates to the nucleus. CRTC2 contains a nuclear localisation sequence (NLS) at amino acids 56-144 as well as two nuclear export sequences (NES1 and NES2) within the region of amino acids 145-320.
Function Transcriptional coactivator for CREB (cAMP-responsive element binding protein).The highly conserved N-terminal coiled-coil domain of the CRTC2 interacts with the bZip domain of CREB which activates both consensus and variant cAMP response element (CRE) sites, leading to activation of CREB target gene expression. CRTC2 responds to stimulation by cAMP, calcium, fasting hormones, G protein-coupled receptors, and AMPK/SIKs.

Implicated in

Note
  
Entity Peutz-Jeghers syndrome
Note Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disorder that is characterised by an increased risk of developing malignant tumours. Most of the identified mutations in the LKB1 gene are localised to the catalytic kinase domain so that it is thought that PJS results from loss of LKB1 kinase activity. The silencing of LKB1, leads to the decreased activity of AMPK and SIK and leads to the increased nuclear translocation and activity of CRTC2.
Disease Gastrointestinal polyps and cancers including esophagus, stomach, small intestine, colon, pancreas, lung, testes, breast, uterus, ovary and cervix.
  
  
Entity Oestrogen-receptor (ER) positive breast cancer
Note The increased prevalence of oestrogen-dependent, postmenopausal breast cancers is correlated with elevated local levels of oestrogens as a result of an increase in cytochrome P450 aromatase expression within the adipose stromal (hAS) cells surrounding the breast tumour - aromatase is the enzyme responsible for the conversion of androgens to oestrogens. This is governed by promoter switching from the distal promoter I.4 to the proximal promoter PII on the CYP19A1 gene, that encodes aromatase, in response to factors derived from the tumour such as prostaglandin E2 (PGE2). Interestingly, the LKB1/ AMPK pathway has been shown to inhibit aromatase expression via the cytoplasmic sequestration of CRTC2. However, PGE2 inhibits LKB1/AMPK signaling, leading to the nuclear translocation of CRTC2 and its enhanced binding and activation of aromatase promoter PII in hAS cells. Furthermore, the adipokine leptin, produced at higher levels in obesity, has been shown to cause an increase in CRTC2 nuclear translocation and consequently, in aromatase expression.
  

Bibliography

LKB1-dependent signaling pathways.
Alessi DR, Sakamoto K, Bayascas JR.
Annu Rev Biochem. 2006;75:137-63.
PMID 16756488
 
Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women.
Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER.
Cancer Res. 2009 Jul 1;69(13):5392-9. Epub 2009 Jun 9.
PMID 19509226
 
Obesity and breast cancer: progress to understanding the relationship.
Brown KA, Simpson ER.
Cancer Res. 2010 Jan 1;70(1):4-7. Epub 2009 Dec 22.
PMID 20028864
 
TORCs: transducers of regulated CREB activity.
Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M.
Mol Cell. 2003 Aug;12(2):413-23.
PMID 14536081
 
Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade.
Katoh Y, Takemori H, Lin XZ, Tamura M, Muraoka M, Satoh T, Tsuchiya Y, Min L, Doi J, Miyauchi A, Witters LA, Nakamura H, Okamoto M.
FEBS J. 2006 Jun;273(12):2730-48.
PMID 16817901
 
The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector.
Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR 3rd, Takemori H, Okamoto M, Montminy M.
Cell. 2004 Oct 1;119(1):61-74.
PMID 15454081
 
Glucose metabolism and cancer.
Shaw RJ.
Curr Opin Cell Biol. 2006 Dec;18(6):598-608. Epub 2006 Oct 12.
PMID 17046224
 
Role of CRE-binding protein (CREB) in aromatase expression in breast adipose.
Sofi M, Young MJ, Papamakarios T, Simpson ER, Clyne CD.
Breast Cancer Res Treat. 2003 Jun;79(3):399-407.
PMID 12846424
 
Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells.
Wu Z, Huang X, Feng Y, Handschin C, Feng Y, Gullicksen PS, Bare O, Labow M, Spiegelman B, Stevenson SC.
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14379-84. Epub 2006 Sep 15.
PMID 16980408
 

Citation

This paper should be referenced as such :
Brown, KA ; Samarageewa, N
CRTC2 (CREB regulated transcription coactivator 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1104-1105.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CRTC2ID50581ch1q21.html


External links

Nomenclature
HGNC (Hugo)CRTC2   27301
Cards
AtlasCRTC2ID50581ch1q21
Entrez_Gene (NCBI)CRTC2  200186  CREB regulated transcription coactivator 2
AliasesTORC-2; TORC2
GeneCards (Weizmann)CRTC2
Ensembl hg19 (Hinxton)ENSG00000160741 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000160741 [Gene_View]  chr1:153947672-153958656 [Contig_View]  CRTC2 [Vega]
ICGC DataPortalENSG00000160741
TCGA cBioPortalCRTC2
AceView (NCBI)CRTC2
Genatlas (Paris)CRTC2
WikiGenes200186
SOURCE (Princeton)CRTC2
Genetics Home Reference (NIH)CRTC2
Genomic and cartography
GoldenPath hg38 (UCSC)CRTC2  -     chr1:153947672-153958656 -  1q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CRTC2  -     1q21.3   [Description]    (hg19-Feb_2009)
EnsemblCRTC2 - 1q21.3 [CytoView hg19]  CRTC2 - 1q21.3 [CytoView hg38]
Mapping of homologs : NCBICRTC2 [Mapview hg19]  CRTC2 [Mapview hg38]
OMIM608972   
Gene and transcription
Genbank (Entrez)AF289574 AK096382 AK223559 AY360172 AY726597
RefSeq transcript (Entrez)NM_181715
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CRTC2
Cluster EST : UnigeneHs.406392 [ NCBI ]
CGAP (NCI)Hs.406392
Alternative Splicing GalleryENSG00000160741
Gene ExpressionCRTC2 [ NCBI-GEO ]   CRTC2 [ EBI - ARRAY_EXPRESS ]   CRTC2 [ SEEK ]   CRTC2 [ MEM ]
Gene Expression Viewer (FireBrowse)CRTC2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)200186
GTEX Portal (Tissue expression)CRTC2
Human Protein AtlasENSG00000160741-CRTC2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ53ET0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ53ET0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ53ET0
Splice isoforms : SwissVarQ53ET0
PhosPhoSitePlusQ53ET0
Domains : Interpro (EBI)TORC    TORC_C    TORC_M    TORC_N   
Domain families : Pfam (Sanger)TORC_C (PF12886)    TORC_M (PF12885)    TORC_N (PF12884)   
Domain families : Pfam (NCBI)pfam12886    pfam12885    pfam12884   
Conserved Domain (NCBI)CRTC2
DMDM Disease mutations200186
Blocks (Seattle)CRTC2
PDB (SRS)4HTM   
PDB (PDBSum)4HTM   
PDB (IMB)4HTM   
PDB (RSDB)4HTM   
Structural Biology KnowledgeBase4HTM   
SCOP (Structural Classification of Proteins)4HTM   
CATH (Classification of proteins structures)4HTM   
SuperfamilyQ53ET0
Human Protein Atlas [tissue]ENSG00000160741-CRTC2 [tissue]
Peptide AtlasQ53ET0
HPRD12347
IPIIPI00783502   IPI00639850   IPI00974482   IPI00978493   
Protein Interaction databases
DIP (DOE-UCLA)Q53ET0
IntAct (EBI)Q53ET0
FunCoupENSG00000160741
BioGRIDCRTC2
STRING (EMBL)CRTC2
ZODIACCRTC2
Ontologies - Pathways
QuickGOQ53ET0
Ontology : AmiGOchromatin binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  gluconeogenesis  transcription, DNA-templated  cAMP response element binding protein binding  viral process  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  glucose homeostasis  histone H3-K9 acetylation  positive regulation of transcription from RNA polymerase II promoter  protein homotetramerization  extracellular exosome  toxin transport  
Ontology : EGO-EBIchromatin binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  gluconeogenesis  transcription, DNA-templated  cAMP response element binding protein binding  viral process  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  glucose homeostasis  histone H3-K9 acetylation  positive regulation of transcription from RNA polymerase II promoter  protein homotetramerization  extracellular exosome  toxin transport  
Pathways : KEGGPI3K-Akt signaling pathway    HTLV-I infection   
REACTOMEQ53ET0 [protein]
REACTOME PathwaysR-HSA-400253 [pathway]   
NDEx NetworkCRTC2
Atlas of Cancer Signalling NetworkCRTC2
Wikipedia pathwaysCRTC2
Orthology - Evolution
OrthoDB200186
GeneTree (enSembl)ENSG00000160741
Phylogenetic Trees/Animal Genes : TreeFamCRTC2
HOVERGENQ53ET0
HOGENOMQ53ET0
Homologs : HomoloGeneCRTC2
Homology/Alignments : Family Browser (UCSC)CRTC2
Gene fusions - Rearrangements
Fusion : MitelmanCRTC2/CREB3L4 [1q21.3/1q21.3]  
Fusion : MitelmanCRTC2/KIAA0907 [1q21.3/1q22]  [t(1;1)(q21;q22)]  
Fusion : MitelmanGATAD2B/CRTC2 [1q21.3/1q21.3]  [t(1;1)(q21;q21)]  
Fusion: TCGACRTC2 1q21.3 KIAA0907 1q22 BRCA
Fusion: TCGAGATAD2B 1q21.3 CRTC2 1q21.3 OV
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCRTC2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CRTC2
dbVarCRTC2
ClinVarCRTC2
1000_GenomesCRTC2 
Exome Variant ServerCRTC2
ExAC (Exome Aggregation Consortium)ENSG00000160741
GNOMAD BrowserENSG00000160741
Genetic variants : HAPMAP200186
Genomic Variants (DGV)CRTC2 [DGVbeta]
DECIPHERCRTC2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCRTC2 
Mutations
ICGC Data PortalCRTC2 
TCGA Data PortalCRTC2 
Broad Tumor PortalCRTC2
OASIS PortalCRTC2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCRTC2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCRTC2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CRTC2
DgiDB (Drug Gene Interaction Database)CRTC2
DoCM (Curated mutations)CRTC2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CRTC2 (select a term)
intoGenCRTC2
NCG5 (London)CRTC2
Cancer3DCRTC2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608972   
Orphanet
MedgenCRTC2
Genetic Testing Registry CRTC2
NextProtQ53ET0 [Medical]
TSGene200186
GENETestsCRTC2
Target ValidationCRTC2
Huge Navigator CRTC2 [HugePedia]
snp3D : Map Gene to Disease200186
BioCentury BCIQCRTC2
ClinGenCRTC2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD200186
Chemical/Pharm GKB GenePA142672073
Clinical trialCRTC2
Miscellaneous
canSAR (ICR)CRTC2 (select the gene name)
Probes
Litterature
PubMed49 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCRTC2
EVEXCRTC2
GoPubMedCRTC2
iHOPCRTC2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:19:26 CEST 2017

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