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 AM... See more...

Aliases for CRTC2 Gene

Aliases for CRTC2 Gene

  • CREB Regulated Transcription Coactivator 2 2 3 5
  • CREB-Regulated Transcription Coactivator 2 3 4
  • TORC-2 3 4
  • TORC2 3 4
  • Transducer Of Regulated CAMP Response Element-Binding Protein (CREB) 2 3
  • Transducer Of Regulated CAMP Response Element-Binding Protein 2 4
  • Transducer Of CREB Protein 2 4

External Ids for CRTC2 Gene

Previous GeneCards Identifiers for CRTC2 Gene

  • GC01M150734
  • GC01M152186
  • GC01M153920
  • GC01M125282

Summaries for CRTC2 Gene

Entrez Gene Summary for CRTC2 Gene

  • 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]

GeneCards Summary for CRTC2 Gene

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 LKB1 signaling events and Mitochondrial Gene Expression. Gene Ontology (GO) annotations related to this gene include cAMP response element binding protein binding. An important paralog of this gene is CRTC1.

UniProtKB/Swiss-Prot Summary for CRTC2 Gene

  • 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).

Gene Wiki entry for CRTC2 Gene

Additional gene information for CRTC2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CRTC2 Gene

Genomics for CRTC2 Gene

GeneHancer (GH) Regulatory Elements for CRTC2 Gene

Promoters and enhancers for CRTC2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CRTC2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CRTC2

Top Transcription factor binding sites by QIAGEN in the CRTC2 gene promoter:
  • ATF6
  • CREB
  • deltaCREB
  • ITF-2
  • POU2F1
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT5A
  • Tal-1beta

Genomic Locations for CRTC2 Gene

Genomic Locations for CRTC2 Gene
chr1:153,947,669-153,958,656
(GRCh38/hg38)
Size:
10,988 bases
Orientation:
Minus strand
chr1:153,920,145-153,931,132
(GRCh37/hg19)
Size:
10,988 bases
Orientation:
Minus strand

Genomic View for CRTC2 Gene

Genes around CRTC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CRTC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CRTC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRTC2 Gene

Proteins for CRTC2 Gene

  • Protein details for CRTC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q53ET0-CRTC2_HUMAN
    Recommended name:
    CREB-regulated transcription coactivator 2
    Protein Accession:
    Q53ET0
    Secondary Accessions:
    • Q6UUV8
    • Q7Z3X7
    • Q8N332

    Protein attributes for CRTC2 Gene

    Size:
    693 amino acids
    Molecular mass:
    73302 Da
    Quaternary structure:
    • Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 (PubMed:15454081). 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction (PubMed:15454081). Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1 (PubMed:15454081). Interacts with SIK2 (PubMed:15454081). Interacts with 14-3-3 proteins, YWHAB and YWHAG (PubMed:15454081, PubMed:18626018). Interacts (probably when phosphorylated at Ser-171) with YWHAE (PubMed:30611118). Interacts with calmodulin-dependent catalytic subunit PPP3CA/calcineurin A (PubMed:15454081, PubMed:30611118). Interaction with COP1 mediates nuclear export and degradation of CRTC2 (By similarity).
    • (Microbial infection) Interaction with the human T-cell leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal transcription activation by Tax.

    Three dimensional structures from OCA and Proteopedia for CRTC2 Gene

neXtProt entry for CRTC2 Gene

Post-translational modifications for CRTC2 Gene

  • 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.
  • Ubiquitination at Lys156
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for CRTC2

No data available for DME Specific Peptides for CRTC2 Gene

Domains & Families for CRTC2 Gene

Gene Families for CRTC2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for CRTC2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CRTC2 Gene

GenScript: Design optimal peptide antigens:
  • Transducer of regulated cAMP response element-binding protein 2 (CRTC2_HUMAN)
  • CRTC2 protein (Q8N332_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q53ET0

UniProtKB/Swiss-Prot:

CRTC2_HUMAN :
  • Belongs to the TORC family.
Family:
  • Belongs to the TORC family.
genes like me logo Genes that share domains with CRTC2: view

Function for CRTC2 Gene

Molecular function for CRTC2 Gene

UniProtKB/Swiss-Prot 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).

Phenotypes From GWAS Catalog for CRTC2 Gene

Gene Ontology (GO) - Molecular Function for CRTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IEA --
GO:0005515 protein binding IPI 18077367
GO:0008140 cAMP response element binding protein binding IBA 21873635
genes like me logo Genes that share ontologies with CRTC2: view
genes like me logo Genes that share phenotypes with CRTC2: view

Animal Models for CRTC2 Gene

MGI Knock Outs for CRTC2:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CRTC2 Gene

Localization for CRTC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CRTC2 Gene

Cytoplasm. Nucleus. Note=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). {ECO:0000269 PubMed:15454081}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CRTC2 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
mitochondrion 2
endoplasmic reticulum 2
extracellular 1
cytoskeleton 1
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CRTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm ISS,IBA --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with CRTC2: view

Pathways & Interactions for CRTC2 Gene

genes like me logo Genes that share pathways with CRTC2: view

Pathways by source for CRTC2 Gene

SIGNOR curated interactions for CRTC2 Gene

Activates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CRTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006094 gluconeogenesis IEA,ISS --
GO:0016032 viral process IEA --
GO:0032793 positive regulation of CREB transcription factor activity ISS,IBA --
GO:0042593 glucose homeostasis IEA,ISS --
GO:0043970 histone H3-K9 acetylation IEA --
genes like me logo Genes that share ontologies with CRTC2: view

Drugs & Compounds for CRTC2 Gene

(12) Drugs for CRTC2 Gene - From: PharmGKB, ApexBio, DGIdb, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cyclosporin A Approved, Investigational, Vet_approved Pharma Antagonist, Inhibition, Inhibitor Immunosuppressive agent, Immunosuppressant drug, Calcineurin inhibitor 0
Tacrolimus Approved, Investigational Pharma 1285
Calcium Approved Nutra 7884
cyclic amp Experimental Pharma 0
QL-IX-55 Pharma TORC1/TORC2 inhibitor 0

(1) ApexBio Compounds for CRTC2 Gene

Compound Action Cas Number
QL-IX-55 TORC1/TORC2 inhibitor 1223002-54-7
genes like me logo Genes that share compounds with CRTC2: view

Drug Products

Transcripts for CRTC2 Gene

mRNA/cDNA for CRTC2 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CRTC2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b · 16c
SP1: - - -
SP2: -
SP3: -
SP4:
SP5: -
SP6:

Relevant External Links for CRTC2 Gene

GeneLoc Exon Structure for
CRTC2

Expression for CRTC2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CRTC2 Gene

mRNA differential expression in normal tissues according to GTEx for CRTC2 Gene

This gene is overexpressed in Whole Blood (x4.2).

Protein differential expression in normal tissues from HIPED for CRTC2 Gene

This gene is overexpressed in Placenta (13.9), CD4 Tcells (13.1), Heart (9.6), and CD8 Tcells (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CRTC2 Gene



Protein tissue co-expression partners for CRTC2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CRTC2

SOURCE GeneReport for Unigene cluster for CRTC2 Gene:

Hs.406392

mRNA Expression by UniProt/SwissProt for CRTC2 Gene:

Q53ET0-CRTC2_HUMAN
Tissue specificity: Most abundantly expressed in the thymus. Present in both B and T-lymphocytes. Highly expressed in HEK293T cells and in insulinomas. High levels also in spleen, ovary, muscle and lung, with highest levels in muscle. Lower levels found in brain, colon, heart, kidney, prostate, small intestine and stomach. Weak expression in liver and pancreas.

Evidence on tissue expression from TISSUES for CRTC2 Gene

  • Liver(4.5)
  • Nervous system(4.5)
  • Muscle(2)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with CRTC2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for CRTC2 Gene

Orthologs for CRTC2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CRTC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CRTC2 31 30
  • 96.64 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CRTC2 31 30
  • 91.2 (n)
OneToMany
-- 31
  • 77 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Crtc2 17 31 30
  • 90.3 (n)
rat
(Rattus norvegicus)
Mammalia Crtc2 30
  • 89.92 (n)
dog
(Canis familiaris)
Mammalia CRTC2 31 30
  • 87.97 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CRTC2 31
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia crtc2 30
  • 67.51 (n)
zebrafish
(Danio rerio)
Actinopterygii CABZ01081897.1 31
  • 54 (a)
OneToMany
CRTC2 (1 of 2) 31
  • 27 (a)
OneToMany
Species where no ortholog for CRTC2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CRTC2 Gene

ENSEMBL:
Gene Tree for CRTC2 (if available)
TreeFam:
Gene Tree for CRTC2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CRTC2: view image

Paralogs for CRTC2 Gene

Paralogs for CRTC2 Gene

(3) SIMAP similar genes for CRTC2 Gene using alignment to 5 proteins:

  • CRTC2_HUMAN
  • H0YDQ8_HUMAN
  • J3KNE6_HUMAN
  • Q5T4K5_HUMAN
  • Q8N332_HUMAN

Pseudogenes.org Pseudogenes for CRTC2 Gene

genes like me logo Genes that share paralogs with CRTC2: view

Variants for CRTC2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for CRTC2 Gene

CRTC2_HUMAN-Q53ET0
Variant Cys-379, under a dominant model, linked to a recessive mutation in LKB1, may be associated with susceptibility to type II or non-insulin-dependent diabetes mellitus (NIDDM).

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CRTC2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs11264680 - p.Met147Val
rs150423770 - p.Arg379Cys

Additional dbSNP identifiers (rs#s) for CRTC2 Gene

Variation tolerance for CRTC2 Gene

Residual Variation Intolerance Score: 27.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.90; 83.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CRTC2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CRTC2

SNP Genotyping and Copy Number Assay Products

No data available for Structural Variations from Database of Genomic Variants (DGV) for CRTC2 Gene

Disorders for CRTC2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for CRTC2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
human t-cell leukemia virus type 1
  • htlv-1
t-cell leukemia
  • leukemia, t-cell, chronic
leukemia
  • leukemias
- elite association - COSMIC cancer census association via MalaCards
Search CRTC2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CRTC2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CRTC2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CRTC2 Gene

Publications for CRTC2 Gene

  1. Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes. (PMID: 17950019) Keshavarz P … Itakura M (Molecular genetics and metabolism 2008) 3 4 23 41 54
  2. Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2. (PMID: 18626018) Jansson D … Screaton RA (Proceedings of the National Academy of Sciences of the United States of America 2008) 3 4 23 54
  3. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. (PMID: 15454081) Screaton RA … Montminy M (Cell 2004) 3 4 23 54
  4. Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. (PMID: 14506290) Iourgenko V … Labow MA (Proceedings of the National Academy of Sciences of the United States of America 2003) 2 3 4 54
  5. TORCs: transducers of regulated CREB activity. (PMID: 14536081) Conkright MD … Montminy M (Molecular cell 2003) 2 3 4 54

Products for CRTC2 Gene