CRTC2

CRTC2 (CREB Regulated Transcription Coactivator 2) is a Protein Coding gene. Diseases associated with CRTC2 include Human T-Cell Leukemia Virus Type 1 and T-Cell Leukemia. Among its related pathways are Metformin Pathway, Pharmacodynamics and Organelle biogenesis and maintenance. Gene Ontology (GO) annotations related to this gene include cAMP response element binding protein binding. An important paralog of this gene is CRTC1.

Full Name

CREB Regulated Transcription Coactivator 2

Function

Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).

Biological Process

Gluconeogenesis Source: UniProtKB
Glucose homeostasis Source: UniProtKB
Histone H3-K9 acetylation Source: Ensembl
Positive regulation of CREB transcription factor activity Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: GO_Central
Protein homotetramerization Source: InterPro
Toxin transport Source: Ensembl
Viral process Source: UniProtKB-KW

Cellular Location

Cytoplasm; Nucleus. Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein (PubMed:15454081). In response to cAMP levels and glucagon, relocated to the nucleus (PubMed:15454081).

PTM

Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity (PubMed:15589160, PubMed:17210223). CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site (PubMed:17210223). This primary site of phosphorylation, is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2) by LKB1 (PubMed:15454081, PubMed:16817901). Following adenylyl cyclase activation, dephosphorylated at Ser-171 by PPP3CA/calcineurin A resulting in CRTC2 dissociation from 14-3-3 proteins and PPP3CA (By similarity). Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it (PubMed:15454081). Phosphorylation at Ser-274 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx (PubMed:18626018). Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm (PubMed:18626018).
Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.