CRTC1 (CREB Regulated Transcription Coactivator 1)
A key transcriptional coactivator in cAMP and calcium signaling pathways, implicated in oncogenic fusions and metabolic regulation.
Gene Information Card
| Symbol | CRTC1 |
|---|---|
| Full Name | CREB regulated transcription coactivator 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 23373 ncbi.nlm.nih.gov/gene/23373 |
| Ensembl ID | ENSG00000105662 |
| UniProt ID | Q6UUV9 |
| OMIM ID | 608536 |
| HGNC ID | 16062 |
| Aliases | MECT1, TORC1, WAMTP1 |
Description
CRTC1 (CREB regulated transcription coactivator 1) encodes a member of the CREB-regulated transcription coactivator family. The protein acts as a coactivator of CREB1 (cAMP response element-binding protein) and is involved in cellular processes such as gluconeogenesis, energy homeostasis, and synaptic plasticity. CRTC1 is activated by dephosphorylation in response to cAMP and calcium signaling, and is sequestered in the cytoplasm under basal conditions. Chromosomal rearrangements involving CRTC1, particularly the t(11;19)(q21;p13) translocation, result in the CRTC1-MAML2 fusion gene, which is a driver in mucoepidermoid carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucoepidermoid Carcinoma | CRTC1-MAML2 fusion (t(11;19)(q21;p13)) produces a chimeric protein that constitutively activates Notch and CREB target genes, promoting tumorigenesis. | Strong; recurrent fusion found in ~50% of mucoepidermoid carcinomas (OMIM #608536, NCBI Gene). |
| Clear Cell Hidradenoma | CRTC1-MAML2 fusion also identified in a subset of clear cell hidradenomas, a benign skin adnexal tumor. | Moderate; case series and molecular studies (COSMIC). |
| Warthin Tumor | CRTC1-MAML2 fusion reported in some Warthin tumors of the salivary gland. | Limited; small cohort studies (COSMIC). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.2 | Medium |
| Heart | 8.1 | Low |
| Liver | 6.3 | Low |
| Testis | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 (embryonic kidney) | 9.8 | Moderate expression |
| HeLa (cervical carcinoma) | 7.2 | Low expression |
| A549 (lung carcinoma) | 6.5 | Low expression |
| MCF7 (breast carcinoma) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CRTC1-MAML2 fusion | Gene fusion | Recurrent in mucoepidermoid carcinoma (~50%) | Constitutive activation of CREB and Notch signaling. |
| p.Arg482* | Nonsense | Rare | Loss of function; predicted to truncate the protein. |
| p.Ser151Ala | Missense | Rare | Alters phosphorylation site; functional impact unknown. |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg482*) are predicted to cause loss of coactivator function.
Gain of Function (GOF)
CRTC1-MAML2 fusion acts as a gain-of-function oncoprotein by constitutive nuclear localization and transcriptional activation.
Dominant Negative (DN)
Not reported for CRTC1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• cAMP signaling pathway (Reactome R-HSA-382556)
• CREB phosphorylation (Reactome R-HSA-111931)
• Notch signaling (via MAML2 fusion partner)
Protein Summary
CRTC1 is a 634-amino acid protein that shuttles between the cytoplasm and nucleus. Under basal conditions, it is phosphorylated and retained in the cytoplasm by 14-3-3 proteins. Upon cAMP or calcium stimulation, it is dephosphorylated and translocates to the nucleus, where it binds CREB and recruits coactivators such as TAF4 to promote transcription of target genes. The protein contains a coiled-coil domain that mediates interaction with CREB and MAML2. The CRTC1-MAML2 fusion retains the N-terminal CREB-binding domain of CRTC1 fused to the C-terminal transcriptional activation domain of MAML2, leading to aberrant activation of Notch target genes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRTC1 Knockout HEK293 Cell Line | EDJ-KQ7991 | Human | 23373 | Details Get a Quote |
| CRTC1 Knockout A-549 Cell Line | EDJ-KQ33720 | Human | 23373 | Details Get a Quote |
| CRTC1 Knockout HCT 116 Cell Line | EDJ-KQ33721 | Human | 23373 | Details Get a Quote |
| CRTC1 Knockout HeLa Cell Line | EDJ-KQ33722 | Human | 23373 | Details Get a Quote |
