CRTC1 (CREB regulated transcription coactivator 1)

2006-05-01   Afrouz Behboudi , Gâran Stenman 

Department of Clinical Genetics, Institute of Biomedicine, Gâteborg University, Box 440, 405 30 Gâteborg, Sweden

Identity

HGNC
LOCATION
19p13.11
LOCUSID
ALIAS
MAML2,MECT1,Mam-2,TORC-1,TORC1,WAMTP1
FUSION GENES

DNA/RNA

Description

Spans about 94 kb and includes 14 to 16 exons

Transcription

two RNA variants of 2505 and 2342 bp, respectively.

Proteins

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 name
Mucoepidermoid carcinoma (most common type of malignant salivary gland tumor; second most frequent lung tumor of bronchial gland origin); benign Warthins 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 gene
CRTC1-MAML2. Exon 1 of MECT1 fused to exons 2-5 of MAML2.
Atlas Image
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 Warthins tumors, 21-28, Copyright (2004), with permission from Elsevier.

Fusion 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.
Atlas Image
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

Pubmed IDLast YearTitleAuthors
164447492006Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.Behboudi A et al
145360812003TORCs: transducers of regulated CREB activity.Conkright MD et al
147205032004Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.Enlund F et al
145062902003Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.Iourgenko V et al
158268372005Fusion oncogenes and tumor type specificity--insights from salivary gland tumors.Stenman G et al
125390492003t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.Tonon G et al
159619992005Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.Wu L et al

Other Information

Locus ID:

NCBI: 23373
MIM: 607536
HGNC: 16062
Ensembl: ENSG00000105662

Variants:

dbSNP: 23373
ClinVar: 23373
TCGA: ENSG00000105662
COSMIC: CRTC1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000105662ENST00000321949Q6UUV9
ENSG00000105662ENST00000338797Q6UUV9
ENSG00000105662ENST00000594658M0QX46
ENSG00000105662ENST00000601916M0QXN6

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Organelle biogenesis and maintenanceREACTOMER-HSA-1852241
Mitochondrial biogenesisREACTOMER-HSA-1592230
Transcriptional activation of mitochondrial biogenesisREACTOMER-HSA-2151201
Circadian ClockREACTOMER-HSA-400253
BMAL1:CLOCK,NPAS2 activates circadian gene expressionREACTOMER-HSA-1368108

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
227495282012Glutaminolysis activates Rag-mTORC1 signaling.207
169804082006Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells.111
125390492003t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.99
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
250839932014p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8⁺ T cells.84
226276712012Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence.67
217989972011Interplay between pVHL and mTORC1 pathways in clear-cell renal cell carcinoma.46
205881782010A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas.42
217060492012Altered LKB1/CREB-regulated transcription co-activator (CRTC) signaling axis promotes esophageal cancer cell migration and invasion.35
168093102006TORC1 and TORC2 coactivators are required for tax activation of the human T-cell leukemia virus type 1 long terminal repeats.34

Citation

Afrouz Behboudi ; Gâran Stenman

CRTC1 (CREB regulated transcription coactivator 1)

Atlas Genet Cytogenet Oncol Haematol. 2006-05-01

Online version: http://atlasgeneticsoncology.org/gene/471/crtc1

Historical Card

2003-07-01 CRTC1 (CREB regulated transcription coactivator 1) by  Goran Stenman 

Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden