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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)


HGNC Alias symbTORC2
LocusID (NCBI) 200186
Atlas_Id 50581
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 153947676 and ends at 153958612 bp from pter ( according to GRCh38/hg38-Dec_2013)  [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)


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


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 (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

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.
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.


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


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 ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(1;1)(q21;q21) CRTC2::CREB3L4

External links


HGNC (Hugo)CRTC2   27301
Entrez_Gene (NCBI)CRTC2    CREB regulated transcription coactivator 2
AliasesTORC-2; TORC2
GeneCards (Weizmann)CRTC2
Ensembl hg19 (Hinxton)ENSG00000160741 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000160741 [Gene_View]  ENSG00000160741 [Sequence]  chr1:153947676-153958612 [Contig_View]  CRTC2 [Vega]
ICGC DataPortalENSG00000160741
TCGA cBioPortalCRTC2
Genatlas (Paris)CRTC2
SOURCE (Princeton)CRTC2
Genetics Home Reference (NIH)CRTC2
Genomic and cartography
GoldenPath hg38 (UCSC)CRTC2  -     chr1:153947676-153958612 -  1q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CRTC2  -     1q21.3   [Description]    (hg19-Feb_2009)
GoldenPathCRTC2 - 1q21.3 [CytoView hg19]  CRTC2 - 1q21.3 [CytoView hg38]
Genome Data Viewer NCBICRTC2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF289574 AK096382 AK223559 AY360172 AY726597
RefSeq transcript (Entrez)NM_181715
Consensus coding sequences : CCDS (NCBI)CRTC2
Gene ExpressionCRTC2 [ NCBI-GEO ]   CRTC2 [ EBI - ARRAY_EXPRESS ]   CRTC2 [ SEEK ]   CRTC2 [ MEM ]
Gene Expression Viewer (FireBrowse)CRTC2 [ Firebrowse - Broad ]
GenevisibleExpression of CRTC2 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
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
PDB Europe4HTM   
Structural Biology KnowledgeBase4HTM   
SCOP (Structural Classification of Proteins)4HTM   
CATH (Classification of proteins structures)4HTM   
AlphaFold pdb e-kbQ53ET0   
Human Protein Atlas [tissue]ENSG00000160741-CRTC2 [tissue]
Protein Interaction databases
IntAct (EBI)Q53ET0
Ontologies - Pathways
Ontology : AmiGOchromatin binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  gluconeogenesis  cAMP response element binding protein binding  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  glucose homeostasis  histone H3-K9 acetylation  positive regulation of transcription by RNA polymerase II  protein homotetramerization  extracellular exosome  toxin transport  
Ontology : EGO-EBIchromatin binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  gluconeogenesis  cAMP response element binding protein binding  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  glucose homeostasis  histone H3-K9 acetylation  positive regulation of transcription by RNA polymerase II  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
GeneTree (enSembl)ENSG00000160741
Phylogenetic Trees/Animal Genes : TreeFamCRTC2
Homologs : HomoloGeneCRTC2
Homology/Alignments : Family Browser (UCSC)CRTC2
Gene fusions - Rearrangements
Fusion : MitelmanCRTC2::CREB3L4 [1q21.3/1q21.3]  
Fusion : MitelmanCRTC2::KIAA0907 [1q21.3/1q22]  
Fusion : MitelmanGATAD2B::CRTC2 [1q21.3/1q21.3]  
Fusion : QuiverCRTC2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCRTC2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CRTC2
Exome Variant ServerCRTC2
GNOMAD BrowserENSG00000160741
Varsome BrowserCRTC2
ACMGCRTC2 variants
Genomic Variants (DGV)CRTC2 [DGVbeta]
DECIPHERCRTC2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCRTC2 
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]  
Somatic Mutations in Cancer : COSMIC3DCRTC2
Mutations and Diseases : HGMDCRTC2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)CRTC2
DoCM (Curated mutations)CRTC2
CIViC (Clinical Interpretations of Variants in Cancer)CRTC2
NCG (London)CRTC2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CRTC2
NextProtQ53ET0 [Medical]
Target ValidationCRTC2
Huge Navigator CRTC2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDCRTC2
Pharm GKB GenePA142672073
Pharm GKB PathwaysPA165948566   
Clinical trialCRTC2
DataMed IndexCRTC2
PubMed72 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:15:26 CEST 2021

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