CRTC1 (CREB regulated transcription coactivator 1)

Identity

Other names	KIAA0616
	FLJ14027
	WAMTP1
	MECT1
	TORC1
Hugo	CRTC1
Location	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

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

External links

	Nomenclature
Hugo	CRTC1
GDB	CRTC1
Entrez_Gene	CRTC1  23373  CREB regulated transcription coactivator 1
	Cards
Atlas	CRTC1ID471ch19p13
GeneCards	CRTC1
Ensembl	CRTC1 [Search_View]   ENSG00000105662 [Gene_View]
Genatlas	CRTC1
GeneLynx	CRTC1
eGenome	CRTC1
euGene	23373
	Genomic and cartography
GoldenPath	CRTC1  -  19p13.11   chr19:18655425-18754143 +  19p13.11   [Description]    (hg18-Mar_2006)
Ensembl	CRTC1 - 19p13.11 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	CRTC1
	Gene and transcription
Genbank	AB014516 [ ENTREZ ]
Genbank	AK024089 [ ENTREZ ]
Genbank	AU118537 [ ENTREZ ]
Genbank	AY040323 [ ENTREZ ]
Genbank	AY360171 [ ENTREZ ]
RefSeq	NM_001098482 [ SRS ]    NM_001098482 [ ENTREZ ]
RefSeq	NM_015321 [ SRS ]    NM_015321 [ ENTREZ ]
RefSeq	NM_025021 [ SRS ]    NM_025021 [ ENTREZ ]
RefSeq	AC_000062 [ SRS ]    AC_000062 [ ENTREZ ]
RefSeq	NC_000019 [ SRS ]    NC_000019 [ ENTREZ ]
RefSeq	NT_011295 [ SRS ]    NT_011295 [ ENTREZ ]
RefSeq	NW_927195 [ SRS ]    NW_927195 [ ENTREZ ]
AceView	CRTC1 AceView - NCBI
Unigene	Hs.371096 [ SRS ]    Hs.371096 [ NCBI ]     HS371096 [ spliceNest ]
Fast-db	9216 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q6UUV9 [ SRS]    Q6UUV9 [ EXPASY ]     Q6UUV9 [ INTERPRO ]
CluSTr	Q6UUV9
Blocks	Q6UUV9
HPRD	06339
	Protein Interaction databases
DIP	Q6UUV9
IntAct	Q6UUV9
	Polymorphism : SNP, mutations, diseases
OMIM	607536    [ map ]
GENECLINICS	607536
SNP	CRTC1 [dbSNP-NCBI]
SNP	NM_001098482 [SNP-NCI]
SNP	NM_015321 [SNP-NCI]
SNP	NM_025021 [SNP-NCI]
SNP	CRTC1 [GeneSNPs - Utah]  CRTC1] [HGBASE - SRS]
HAPMAP	CRTC1 [HAPMAP]
COSMIC	CRTC1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	CRTC1
	General knowledge
Family Browser	CRTC1 [UCSC Family Browser]
SOURCE	NM_001098482
SOURCE	NM_015321
SOURCE	NM_025021
SMD	Hs.371096
SAGE	Hs.371096
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	cAMP response element binding protein binding [Amigo]  cAMP response element binding protein binding
GO	positive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
PubGene	CRTC1
TreeFam	CRTC1
CTD	23373 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	CRTC1 Related clones (RZPD - Berlin)
	PubMed
PubMed	23 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	07-2003	Goran Stenman
		Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden

Citation

This paper should be referenced as such :

Stenman G . CRTC1 (CREB regulated transcription coactivator 1). Atlas Genet Cytogenet Oncol Haematol. July 2003 . URL : http://AtlasGeneticsOncology.org/Genes/CRTC1ID471ch19p13.html

Behboudi A, Stenman G . CRTC1 (CREB regulated transcription coactivator 1). Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/CRTC1ID471ch19p13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:22:52 2008