CRTC2 Gene

Name	CREB regulated transcription coactivator 2
Description	This gene encodes a member of the transducers of regulated cAMP response element-binding protein activity family of transcription coactivators. These proteins promote the transcription of genes targeted by the cAMP response element-binding protein, and therefore play an important role in many cellular processes. Under basal conditions the encoded protein is phosphorylated by AMP-activated protein kinase or the salt-inducible kinases and is sequestered in the cytoplasm. Upon activation by elevated cAMP or calcium, the encoded protein translocates to the nucleus and increases target gene expression. Single nucleotide polymorphisms in this gene may increase the risk of type 2 diabetes. A pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CRTC2 is a CREB‐regulated transcription coactivator that plays a central role in coupling nutrient and hormonal signals to gene expression programs governing both glucose and lipid metabolism. In response to fasting and glucagon stimulation, CRTC2 is dephosphorylated and translocates into the nucleus where it binds to CREB and activates gluconeogenic gene transcription to help maintain blood glucose levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Under hyperglycemic conditions, however, CRTC2 becomes O‐linked glycosylated—a modification that counteracts its inhibitory phosphorylation and locks it in an active conformation, thereby further stimulating hepatic gluconeogenesis and contributing to glucose intolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, CRTC2 functions as a dual sensor by integrating signals from both fasting and endoplasmic reticulum stress pathways; through its association with ATF6α, CRTC2 not only promotes the expression of gluconeogenic genes but also induces ER quality control genes, thereby fine‐tuning hepatic glucose output under metabolic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition to its classical role in glucose metabolism, CRTC2 has been implicated in the regulation of lipid homeostasis: during feeding, mTOR‐mediated phosphorylation of CRTC2 relieves its inhibitory effect on COPII‐dependent processing of SREBP1, which in turn modulates lipogenic programs and insulin sensitivity in obesity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Beyond the liver, CRTC2 also contributes to the regulation of corticotropin‐releasing hormone expression within the hypothalamic–pituitary–adrenal axis, acting as a molecular switch in response to inputs from BDNF and glucocorticoids."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted physiological roles of CRTC2 in metabolic regulation and highlight its potential as a therapeutic target in disorders characterized by impaired glucose and lipid homeostasis, such as type 2 diabetes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eric E Zhang, Yi Liu, Renaud Dentin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2214"}], "href": "https://doi.org/10.1038/nm.2214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20852621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20852621"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yiguo Wang, Hiroshi Inoue, Kim Ravnskjaer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0914897107"}], "href": "https://doi.org/10.1073/pnas.0914897107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20133702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20133702"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Renaud Dentin, Susan Hedrick, Jianxin Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic glucose sensing via the CREB coactivator CRTC2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1151363"}], "href": "https://doi.org/10.1126/science.1151363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18323454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18323454"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yiguo Wang, Liliana Vera, Wolfgang H Fischer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08111"}], "href": "https://doi.org/10.1038/nature08111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19543265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19543265"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jinbo Han, Erwei Li, Liqun Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature14557"}], "href": "https://doi.org/10.1038/nature14557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26147081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26147081"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Freddy D Jeanneteau, W Marcus Lambert, Naima Ismaili, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1114122109"}], "href": "https://doi.org/10.1073/pnas.1114122109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22232675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22232675"}]}]}]}
Synonyms	TORC2, TORC-2
Proteins	CRTC2_HUMAN
NCBI Gene ID	200186
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRTC2 has 5,421 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

Click the + buttons to view associations for CRTC2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CRTC2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRTC2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRTC2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CRTC2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CRTC2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CRTC2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRTC2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRTC2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRTC2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRTC2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CRTC2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CRTC2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRTC2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRTC2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CRTC2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CRTC2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRTC2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CRTC2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CRTC2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRTC2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CRTC2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRTC2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRTC2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRTC2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRTC2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CRTC2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CRTC2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CRTC2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRTC2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CRTC2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CRTC2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRTC2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CRTC2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRTC2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CRTC2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CRTC2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CRTC2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CRTC2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CRTC2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CRTC2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of CRTC2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.