CRTC2: CREB-Regulated Transcription Coactivator 2
A key regulator of gluconeogenesis and energy metabolism, implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | CRTC2 |
|---|---|
| Full Name | CREB regulated transcription coactivator 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 200186 ncbi.nlm.nih.gov/gene/200186 |
| Ensembl ID | ENSG00000143157 |
| UniProt ID | Q53ET0 |
| OMIM ID | 608972 |
| HGNC ID | 25182 |
| Aliases | TORC2, MGC138687, MGC138689 |
Description
CRTC2 (CREB regulated transcription coactivator 2) is a member of the CRTC family of transcriptional coactivators that enhance the activity of CREB (cAMP response element-binding protein). It plays a critical role in gluconeogenesis by promoting the expression of gluconeogenic enzymes in the liver. CRTC2 is regulated by phosphorylation and subcellular localization, and its dysregulation is linked to metabolic disorders such as type 2 diabetes and obesity, as well as certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | CRTC2 overactivation increases gluconeogenic gene expression, contributing to hyperglycemia. | NCBI Gene, OMIM |
| Obesity | Altered CRTC2 signaling in adipose tissue affects energy balance and insulin sensitivity. | NCBI Gene |
| Hepatocellular Carcinoma | CRTC2 overexpression promotes cell proliferation and survival via CREB target genes. | COSMIC, NCBI Gene |
| Colorectal Cancer | CRTC2 amplification or overexpression correlates with poor prognosis and metastasis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose Tissue | 8.3 | Low |
| Pancreas | 6.1 | Low |
| Kidney | 10.2 | Medium |
| Brain | 4.7 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.8 | Liver cancer cell line; high expression |
| HEK293 | 9.4 | Embryonic kidney; moderate expression |
| MCF7 | 7.2 | Breast cancer; moderate expression |
| HeLa | 5.6 | Cervical cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.1% | Altered phosphorylation and nuclear localization |
| c.1246G>A (p.Glu416Lys) | Missense | <0.1% | Potential gain-of-function in cancer |
| c.1570_1571insA | Frameshift | <0.1% | Loss-of-function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations leading to premature stop codons reduce coactivator activity.
Gain of Function (GOF)
Missense mutations that enhance nuclear localization or CREB binding increase gluconeogenic gene expression.
Dominant Negative (DN)
Not well documented; some truncations may interfere with wild-type CRTC2 function.
View complete mutation data：
Gene Ontology (GO)
| • transcription coactivator activity | • cAMP response element binding |
| • regulation of gluconeogenesis | • positive regulation of transcription by RNA polymerase II |
| • nucleus | • cytoplasm |
Pathways
• CREB signaling pathway
• Gluconeogenesis
• Insulin signaling
• cAMP-mediated signaling
Protein Summary
CRTC2 is a 693-amino acid protein that shuttles between the cytoplasm and nucleus. In its dephosphorylated state, it translocates to the nucleus and binds CREB, enhancing transcription of target genes such as PCK1 and G6PC. Phosphorylation by SIK kinases retains it in the cytoplasm. The protein contains a coiled-coil domain for CREB interaction and a nuclear localization signal.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRTC2 Knockout HEK293 Cell Line | EDJ-KQ788 | Human | 200186 | Details Get a Quote |
| CRTC2 Knockout HeLa Cell Line | EDJ-KQ18350 | Human | 200186 | Details Get a Quote |
| CRTC2 Knockout A-549 Cell Line | EDJ-KQ19498 | Human | 200186 | Details Get a Quote |
| CRTC2 Knockout HCT 116 Cell Line | EDJ-KQ19499 | Human | 200186 | Details Get a Quote |
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