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CRTC1 (CREB regulated transcription coactivator 1)

Written2003-07Goran Stenman
Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden
Updated2006-05Afrouz Behboudi, Gâran Stenman
Department of Clinical Genetics, Institute of Biomedicine, Gâteborg University, Box 440, 405 30 Gâteborg, Sweden

(Note : for Links provided by Atlas : click)

Identity

Other namesKIAA0616
FLJ14027
WAMTP1
MECT1
TORC1
HGNC (Hugo) CRTC1
LocusID (NCBI) 23373
Atlas_Id 471
Location 19p13.11  [Link to chromosome band 19p13]
Location_base_pair Starts at 18794425 and ends at 18893143 bp from pter ( according to hg19-Feb_2009)  [Mapping CRTC1.png]
Fusion genes
(updated 2016)
CRTC1 (19p13.11) / CRTC1 (19p13.11)CRTC1 (19p13.11) / EWSR1 (22q12.2)CRTC1 (19p13.11) / KLHL26 (19p13.11)
CRTC1 (19p13.11) / LYPD4 (19q13.2)CRTC1 (19p13.11) / MAML2 (11q21)CRTC1 (19p13.11) / SORCS2 (4p16.1)
CRTC1 (19p13.11) / TMEM59L (19p13.11)MAML2 (11q21) / CRTC1 (19p13.11)

DNA/RNA

Description Spans about 94 kb and includes 14 to 16 exons
Transcription two RNA variants of 2505 and 2342 bp, respectively.

Protein

Note 634 amino acids; 67300 Da
Description Transcriptional coactivator for CREB1.
Expression Expressed in a restricted number of tissues including fetal brain and liver and adult heart, skeletal muscle, liver and salivary gland.
Localisation Nucleus.
Function Interacts through its N-terminal CREB-binding domain with the bZIP domain of CREB1; Binds to CREB1 as a homotetramer. Transcriptional coactivator for CREB1, which activates transcription through both consensus and variant cAMP response element (CRE) sites, leading to activation of CREB1 target genes. Does not appear to modulate CREB1 DNA-binding activity but enhances the interaction of CREB1 with TAF4/TAFII-130.

Implicated in

Note
Entity Mucoepidermoid carcinoma (most common type of malignant salivary gland tumor; second most frequent lung tumor of bronchial gland origin); benign Warthin's tumor; clear cell hidradenoma of the skin (CCH; a.k.a. nodular hidradenomas or eccrine acrospiromas). all sharing a t(11; 19) (q21; p13)
Cytogenetics t(11;19)(q21;p13).
Hybrid/Mutated Gene CRTC1-MAML2. Exon 1 of MECT1 fused to exons 2-5 of MAML2.
 
Fig1a (a) Partial G-banded and SKY karyotypes showing the t(11;19) in a mucoepidermoid carcinoma (MEC) case. (b) Dual-color FISH experiment of the MEC using BAC 697H10 (MAML2, red signal) and cosmid LLNLR 255A4 (CRTC1, green signal) as probes. Note the presence of the CRTC1-MAML2 fusion gene on the der(11) (fused red green signals marked by an arrowhead).
Reprinted partially from Publication 'Exp Cell Res 292, Enlund F., Behboudi A., Andren Y., Oberg C., Lendahl U., Mark J., Stenman G., Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors, 21-28, Copyright (2004), with permission from Elsevier.'

Abnormal Protein MECT1-MAML2; in the fusion protein the first 171 aa including the basic domain of MAML2 are replaced by 42 aa of MECT1; there are no sequence similarities in the N-terminal domains of MAML2 and MECT1; the fusion protein activates transcription of the Notch target gene HES1 independently of both Notch ligand and CSL.
 
Top: Nucleotide and deduced amino acid sequences of the CRTC1-MAML2 breakpoint junction.
Bottom: Schematic representation of the MAML2 protein and the CRTC1-MAML2 fusion protein. In the fusion protein the N-terminal Notch-binding domain of MAML2 is replaced by the CREB-binding domain of CRTC1.
Reprinted partially from publication above mentioned
  

Bibliography

Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
Behboudi A, Enlund F, Winnes M, Andrén Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Mäkitie A, Grenman R, Mark J, Stenman G
Genes, chromosomes & cancer. 2006 ; 45 (5) : 470-481.
PMID 16444749
 
TORCs: transducers of regulated CREB activity.
Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M
Molecular cell. 2003 ; 12 (2) : 413-423.
PMID 14536081
 
Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
Enlund F, Behboudi A, Andrén Y, Oberg C, Lendahl U, Mark J, Stenman G
Experimental cell research. 2004 ; 292 (1) : 21-28.
PMID 14720503
 
Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.
Iourgenko V, Zhang W, Mickanin C, Daly I, Jiang C, Hexham JM, Orth AP, Miraglia L, Meltzer J, Garza D, Chirn GW, McWhinnie E, Cohen D, Skelton J, Terry R, Yu Y, Bodian D, Buxton FP, Zhu J, Song C, Labow MA
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (21) : 12147-12152.
PMID 14506290
 
Fusion oncogenes and tumor type specificity--insights from salivary gland tumors.
Stenman G
Seminars in cancer biology. 2005 ; 15 (3) : 224-235.
PMID 15826837
 
t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.
Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, O'Neil K, Stover K, El-Naggar A, Griffin JD, Kirsch IR, Kaye FJ
Nature genetics. 2003 ; 33 (2) : 208-213.
PMID 12539049
 
Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.
Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, Griffin JD
The EMBO journal. 2005 ; 24 (13) : 2391-2402.
PMID 15961999
 

Citation

This paper should be referenced as such :
Behboudi, A ; Stenman, G
CRTC1 (CREB regulated transcription coactivator 1)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):222-223.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CRTC1ID471ch19p13.html
History of this paper:
Stenman, G. CRTC1 (CREB regulated transcription coactivator 1). Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):171-171.
http://documents.irevues.inist.fr/bitstream/handle/2042/37985/07-2003-CRTC1ID471ch19p13.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]
  Skin: Clear cell hidradenoma
Head and Neck: Salivary gland tumors: an overview
Head and Neck: Salivary gland tumors: Mucoepidermoid carcinoma with t(6;22)(p21;q12) EWSR1/POU5F1
Head and Neck: Salivary gland tumors: Warthin's tumors

External links

Nomenclature
HGNC (Hugo)CRTC1   16062
Cards
AtlasCRTC1ID471ch19p13
Entrez_Gene (NCBI)CRTC1  23373  CREB regulated transcription coactivator 1
AliasesMECT1; TORC-1; TORC1; WAMTP1
GeneCards (Weizmann)CRTC1
Ensembl hg19 (Hinxton)ENSG00000105662 [Gene_View]  chr19:18794425-18893143 [Contig_View]  CRTC1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000105662 [Gene_View]  chr19:18794425-18893143 [Contig_View]  CRTC1 [Vega]
ICGC DataPortalENSG00000105662
TCGA cBioPortalCRTC1
AceView (NCBI)CRTC1
Genatlas (Paris)CRTC1
WikiGenes23373
SOURCE (Princeton)CRTC1
Genomic and cartography
GoldenPath hg19 (UCSC)CRTC1  -     chr19:18794425-18893143 +  19p13   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)CRTC1  -     19p13   [Description]    (hg38-Dec_2013)
EnsemblCRTC1 - 19p13 [CytoView hg19]  CRTC1 - 19p13 [CytoView hg38]
Mapping of homologs : NCBICRTC1 [Mapview hg19]  CRTC1 [Mapview hg38]
OMIM607536   
Gene and transcription
Genbank (Entrez)AB014516 AK024089 AU118537 AY040323 AY186998
RefSeq transcript (Entrez)NM_001098482 NM_015321 NM_025021
RefSeq genomic (Entrez)NC_000019 NC_018930 NT_011295 NW_004929414
Consensus coding sequences : CCDS (NCBI)CRTC1
Cluster EST : UnigeneHs.371096 [ NCBI ]
CGAP (NCI)Hs.371096
Alternative Splicing GalleryENSG00000105662
Gene ExpressionCRTC1 [ NCBI-GEO ]   CRTC1 [ EBI - ARRAY_EXPRESS ]   CRTC1 [ SEEK ]   CRTC1 [ MEM ]
Gene Expression Viewer (FireBrowse)CRTC1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23373
GTEX Portal (Tissue expression)CRTC1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6UUV9 (Uniprot)
NextProtQ6UUV9  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ6UUV9
Splice isoforms : SwissVarQ6UUV9 (Swissvar)
PhosPhoSitePlusQ6UUV9
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   
DMDM Disease mutations23373
Blocks (Seattle)CRTC1
SuperfamilyQ6UUV9
Human Protein AtlasENSG00000105662
Peptide AtlasQ6UUV9
HPRD06339
IPIIPI00783099   IPI00412329   IPI00303383   
Protein Interaction databases
DIP (DOE-UCLA)Q6UUV9
IntAct (EBI)Q6UUV9
FunCoupENSG00000105662
BioGRIDCRTC1
STRING (EMBL)CRTC1
ZODIACCRTC1
Ontologies - Pathways
QuickGOQ6UUV9
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  plasma membrane  transcription, DNA-templated  memory  cAMP response element binding protein binding  viral process  dendrite  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  neuronal cell body  entrainment of circadian clock by photoperiod  synapse  positive regulation of transcription from RNA polymerase II promoter  rhythmic process  protein homotetramerization  membrane hyperpolarization  positive regulation of dendrite development  positive regulation of long-term synaptic potentiation  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  cytoplasm  cytoplasm  plasma membrane  transcription, DNA-templated  memory  cAMP response element binding protein binding  viral process  dendrite  positive regulation of CREB transcription factor activity  positive regulation of CREB transcription factor activity  neuronal cell body  entrainment of circadian clock by photoperiod  synapse  positive regulation of transcription from RNA polymerase II promoter  rhythmic process  protein homotetramerization  membrane hyperpolarization  positive regulation of dendrite development  positive regulation of long-term synaptic potentiation  
Pathways : KEGGHTLV-I infection   
NDEx Network
Atlas of Cancer Signalling NetworkCRTC1
Wikipedia pathwaysCRTC1
Orthology - Evolution
OrthoDB23373
GeneTree (enSembl)ENSG00000105662
Phylogenetic Trees/Animal Genes : TreeFamCRTC1
Homologs : HomoloGeneCRTC1
Homology/Alignments : Family Browser (UCSC)CRTC1
Gene fusions - Rearrangements
Fusion : MitelmanCRTC1/KLHL26 [19p13.11/19p13.11]  
Fusion : MitelmanCRTC1/LYPD4 [19p13.11/19q13.2]  [t(19;19)(p13;q13)]  
Fusion : MitelmanCRTC1/MAML2 [19p13.11/11q21]  [t(11;19)(q21;p13)]  
Fusion : COSMICMAML2 [11q21]  -  CRTC1 [19p13.11]  [fusion_1106]  [fusion_1107]  
Fusion: TCGACRTC1 19p13.11 KLHL26 19p13.11 GBM
Fusion: TCGACRTC1 19p13.11 LYPD4 19q13.2 LUSC
Fusion : TICdbCRTC1 [19p13.11]  -  MAML2 [11q21]
Polymorphisms : SNP, variants
NCBI Variation ViewerCRTC1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CRTC1
dbVarCRTC1
ClinVarCRTC1
1000_GenomesCRTC1 
Exome Variant ServerCRTC1
ExAC (Exome Aggregation Consortium)CRTC1 (select the gene name)
Genetic variants : HAPMAP23373
Genomic Variants (DGV)CRTC1 [DGVbeta]
Mutations
ICGC Data PortalCRTC1 
TCGA Data PortalCRTC1 
Broad Tumor PortalCRTC1
OASIS PortalCRTC1 [ Somatic mutations - Copy number]
Cancer Gene: CensusCRTC1 
Somatic Mutations in Cancer : COSMICCRTC1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CRTC1
DgiDB (Drug Gene Interaction Database)CRTC1
DoCM (Curated mutations)CRTC1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CRTC1 (select a term)
intoGenCRTC1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)19:18794425-18893143  ENSG00000105662
CONAN: Copy Number AnalysisCRTC1 
Mutations and Diseases : HGMDCRTC1
OMIM607536   
MedgenCRTC1
Genetic Testing Registry CRTC1
NextProtQ6UUV9 [Medical]
TSGene23373
GENETestsCRTC1
Huge Navigator CRTC1 [HugePedia]
snp3D : Map Gene to Disease23373
BioCentury BCIQCRTC1
ClinGenCRTC1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23373
Chemical/Pharm GKB GenePA30730
Clinical trialCRTC1
Miscellaneous
canSAR (ICR)CRTC1 (select the gene name)
Probes
Litterature
PubMed69 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCRTC1
EVEXCRTC1
GoPubMedCRTC1
iHOPCRTC1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Aug 10 19:01:07 CEST 2016

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