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CRTC1 (CREB regulated transcription coactivator 1)

Identity

Other namesKIAA0616
FLJ14027
WAMTP1
MECT1
TORC1
HGNC (Hugo) CRTC1
LocusID (NCBI) 23373
Location 19p13.11
Location_base_pair Starts at 18794425 and ends at 18893143 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

Entity Mucoepidermoid carcinoma (most common type of malignant salivary gland tumor; second most frequent lung tumor of bronchial gland origin); benign Warthin¹s 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).
 
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 red­green signals marked by an arrowhead).
Reprinted partially from Publication ³Exp 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.²

Hybrid/Mutated Gene CRTC1-MAML2. Exon 1 of MECT1 fused to exons 2-5 of MAML2.
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
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

External links

Nomenclature
HGNC (Hugo)CRTC1   16062
Cards
AtlasCRTC1ID471ch19p13
Entrez_Gene (NCBI)CRTC1  23373  CREB regulated transcription coactivator 1
GeneCards (Weizmann)CRTC1
Ensembl (Hinxton)ENSG00000105662 [Gene_View]  chr19:18794425-18893143 [Contig_View]  CRTC1 [Vega]
ICGC DataPortalENSG00000105662
cBioPortalCRTC1
AceView (NCBI)CRTC1
Genatlas (Paris)CRTC1
WikiGenes23373
SOURCE (Princeton)NM_001098482 NM_015321 NM_025021
Genomic and cartography
GoldenPath (UCSC)CRTC1  -  19p13.11   chr19:18794425-18893143 +  19p13   [Description]    (hg19-Feb_2009)
EnsemblCRTC1 - 19p13 [CytoView]
Mapping of homologs : NCBICRTC1 [Mapview]
OMIM607536   
Gene and transcription
Genbank (Entrez)AB014516 AK024089 AU118537 AY040323 AY186998
RefSeq transcript (Entrez)NM_001098482 NM_015321 NM_025021
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NT_011295 NW_001838484 NW_004929414
Consensus coding sequences : CCDS (NCBI)CRTC1
Cluster EST : UnigeneHs.371096 [ NCBI ]
CGAP (NCI)Hs.371096
Alternative Splicing : Fast-db (Paris)GSHG0014720
Alternative Splicing GalleryENSG00000105662
Gene ExpressionCRTC1 [ NCBI-GEO ]     CRTC1 [ SEEK ]   CRTC1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6UUV9 (Uniprot)
NextProtQ6UUV9  [Medical]
With graphics : InterProQ6UUV9
Splice isoforms : SwissVarQ6UUV9 (Swissvar)
Domains : Interpro (EBI)TORC [organisation]   TORC_C [organisation]   TORC_M [organisation]   TORC_N [organisation]  
Related proteins : CluSTrQ6UUV9
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)Q6UUV9
Human Protein AtlasENSG00000105662 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ6UUV9
HPRD06339
IPIIPI00783099   IPI00412329   IPI00303383   
Protein Interaction databases
DIP (DOE-UCLA)Q6UUV9
IntAct (EBI)Q6UUV9
FunCoupENSG00000105662
BioGRIDCRTC1
InParanoidQ6UUV9
Interologous Interaction database Q6UUV9
IntegromeDBCRTC1
STRING (EMBL)CRTC1
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  nucleolus  cytoplasm  plasma membrane  transcription, DNA-templated  cAMP response element binding protein binding  viral process  positive regulation of CREB transcription factor activity  positive regulation of transcription from RNA polymerase II promoter  protein homotetramerization  
Ontology : EGO-EBIprotein binding  nucleus  nucleolus  cytoplasm  plasma membrane  transcription, DNA-templated  cAMP response element binding protein binding  viral process  positive regulation of CREB transcription factor activity  positive regulation of transcription from RNA polymerase II promoter  protein homotetramerization  
Pathways : KEGGHTLV-I infection   
Protein Interaction DatabaseCRTC1
Wikipedia pathwaysCRTC1
Gene fusion - rearrangments
Rearrangement : COSMICCRTC1 [19p13.11]  -  MAML2 [11q21]  
  [COSF1102] [COSF1103] 
Rearrangement : COSMICMAML2 [11q21]  -  CRTC1 [19p13.11]  
  [COSF1106] [COSF1107] 
Rearrangement : TICdbCRTC1 [19p13.11]  -  MAML2 [9p24.1]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CRTC1
snp3D : Map Gene to Disease23373
SNP (GeneSNP Utah)CRTC1
SNP : HGBaseCRTC1
Genetic variants : HAPMAPCRTC1
Exome VariantCRTC1
1000_GenomesCRTC1 
ICGC programENSG00000105662 
Cancer Gene: CensusCRTC1 
Somatic Mutations in Cancer : COSMICCRTC1 
CONAN: Copy Number AnalysisCRTC1 
Mutations and Diseases : HGMDCRTC1
Genomic VariantsCRTC1  CRTC1 [DGVbeta]
dbVarCRTC1
ClinVarCRTC1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM607536   
MedgenCRTC1
GENETestsCRTC1
Disease Genetic AssociationCRTC1
Huge Navigator CRTC1 [HugePedia]  CRTC1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneCRTC1
Homology/Alignments : Family Browser (UCSC)CRTC1
Phylogenetic Trees/Animal Genes : TreeFamCRTC1
Chemical/Protein Interactions : CTD23373
Chemical/Pharm GKB GenePA30730
Clinical trialCRTC1
Cancer Resource (Charite)ENSG00000105662
Other databases
Probes
Litterature
PubMed60 Pubmed reference(s) in Entrez
CoreMineCRTC1
iHOPCRTC1
OncoSearchCRTC1

Bibliography

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
 
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
 
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
 
Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
Enlund F, Behboudi A, Andrˆ©n Y, Oberg C, Lendahl U, Mark J, Stenman G
Experimental cell research. 2004 ; 292 (1) : 21-28.
PMID 14720503
 
Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion.
Behboudi A, Winnes M, Gorunova L, van den Oord JJ, Mertens F, Enlund F, Stenman G
Genes, chromosomes & cancer. 2005 ; 43 (2) : 202-205.
PMID 15729701
 
Fusion oncogenes and tumor type specificity--insights from salivary gland tumors.
Stenman G
Seminars in cancer biology. 2005 ; 15 (3) : 224-235.
PMID 15826837
 
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
 
Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
Behboudi A, Enlund F, Winnes M, Andrˆ©n Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Mˆ§kitie A, Grenman R, Mark J, Stenman G
Genes, chromosomes & cancer. 2006 ; 45 (5) : 470-481.
PMID 16444749
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2003Goran Stenman
Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden
Updated05-2006Afrouz Behboudi, Göran Stenman

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 online version   Free pdf version   [Bibliographic record ]
History of this paper:
Behboudi, A ; Stenman, G. CRTC1 (CREB regulated transcription coactivator 1). Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):222-223.
http://documents.irevues.inist.fr/bitstream/handle/2042/37985/07-2003-CRTC1ID471ch19p13.pdf
URL : http://AtlasGeneticsOncology.org/Genes/CRTC1ID471ch19p13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 30 17:03:42 CEST 2014

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