CRTC1 (CREB regulated transcription coactivator 1)

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CRTC1 (CREB regulated transcription coactivator 1)

2006-05-01 Afrouz Behboudi , Gâran Stenman Affiliation

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

Show Gene Fusions

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 ID	Last Year	Title	Authors
16444749	2006	Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.	Behboudi A et al
14536081	2003	TORCs: transducers of regulated CREB activity.	Conkright MD et al
14720503	2004	Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.	Enlund F et al
14506290	2003	Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.	Iourgenko V et al
15826837	2005	Fusion oncogenes and tumor type specificity--insights from salivary gland tumors.	Stenman G et al
12539049	2003	t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.	Tonon G et al
15961999	2005	Transforming 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 ID	Transcript ID	Uniprot
ENSG00000105662	ENST00000321949	Q6UUV9
ENSG00000105662	ENST00000338797	Q6UUV9
ENSG00000105662	ENST00000594658	M0QX46
ENSG00000105662	ENST00000601916	M0QXN6

Expression (GTEx)

0

50

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
HTLV-I infection	KEGG	ko05166
HTLV-I infection	KEGG	hsa05166
Organelle biogenesis and maintenance	REACTOME	R-HSA-1852241
Mitochondrial biogenesis	REACTOME	R-HSA-1592230
Transcriptional activation of mitochondrial biogenesis	REACTOME	R-HSA-2151201
Circadian Clock	REACTOME	R-HSA-400253
BMAL1:CLOCK,NPAS2 activates circadian gene expression	REACTOME	R-HSA-1368108

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
36675234	2023	Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.	0
36675234	2023	Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.	0
34657306	2022	Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.	8
35993578	2022	Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases.	3
36115844	2022	Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma.	7
34657306	2022	Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.	8
35993578	2022	Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases.	3
36115844	2022	Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma.	7
33473104	2021	Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.	10
33556406	2021	Structural Insights into the Interaction Between CRTCs and 14-3-3.	5
33561653	2021	mTORC1 silencing during intestinal epithelial Caco-2 cell differentiation is mediated by the activation of the AMPK/TSC2 pathway.	2
33830080	2021	The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.	25
33473104	2021	Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.	10
33556406	2021	Structural Insights into the Interaction Between CRTCs and 14-3-3.	5
33561653	2021	mTORC1 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/img/favicon/js/lib/jquery-3.5.1.min.js

Historical Card

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

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