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

Article Bibliography

Pubmed IDLast YearTitleAuthors

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
366752342023Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.0
366752342023Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.0
346573062022Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.8
359935782022Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases.3
361158442022Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma.7
346573062022Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.8
359935782022Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases.3
361158442022Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma.7
334731042021Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.10
335564062021Structural Insights into the Interaction Between CRTCs and 14-3-3.5
335616532021mTORC1 silencing during intestinal epithelial Caco-2 cell differentiation is mediated by the activation of the AMPK/TSC2 pathway.2
338300802021The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.25
334731042021Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.10
335564062021Structural Insights into the Interaction Between CRTCs and 14-3-3.5
335616532021mTORC1 silencing during intestinal epithelial Caco-2 cell differentiation is mediated by the activation of the AMPK/TSC2 pathway.2

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/gene-explorer/js/lib/js/web-card-_common.js

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