Human Gene CRTC2 (uc021pab.1) Description and Page Index
  Description: Homo sapiens CREB regulated transcription coactivator 2 (CRTC2), mRNA.
RefSeq Summary (NM_181715): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BC053562.1, SRR1803611.28709.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000368633.2/ ENSP00000357622.1 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr1:153,920,148-153,931,132 Size: 10,985 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg19 chr1:153,920,585-153,930,973 Size: 10,389 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:153,920,148-153,931,132)mRNA (may differ from genome)Protein (693 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=CREB-regulated transcription coactivator 2; AltName: Full=Transducer of regulated cAMP response element-binding protein 2; Short=TORC-2; Short=Transducer of CREB protein 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).
SUBUNIT: Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1 (By similarity). Interacts with PPP3CA/calcineurin alpha, SIK2 and 14-3-3 proteins, YWHAB and YWHAG. Interaction with the human T-cell leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal transcription activation by Tax. Interaction with RFWD2/COP1 mediates nuclear export and degradation of CRTC2 (By similarity).
INTERACTION: P57059:SIK1; NbExp=1; IntAct=EBI-1181987, EBI-1181640; Q9Y2K2:SIK3; NbExp=1; IntAct=EBI-1181987, EBI-1181460;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein. In response to cAMP levels and glucagon, relocated to the nucleus.
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.
PTM: Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity. TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. 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. Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it. Phosphorylation at Ser-274 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx. Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm.
POLYMORPHISM: 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).
SIMILARITY: Belongs to the TORC family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CRTC2
CDC HuGE Published Literature: CRTC2

-  MalaCards Disease Associations
  MalaCards Gene Search: CRTC2
Diseases sorted by gene-association score: human t-cell leukemia virus type 1 (29), t-cell leukemia (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 45.52 RPKM in Spleen
Total median expression: 1080.12 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -79.90159-0.503 Picture PostScript Text
3' UTR -163.40437-0.374 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024786 - TORC
IPR024785 - TORC_C
IPR024784 - TORC_M
IPR024783 - TORC_N

Pfam Domains:
PF12884 - Transducer of regulated CREB activity, N terminus
PF12885 - Transducer of regulated CREB activity middle domain
PF12886 - Transducer of regulated CREB activity, C terminus

ModBase Predicted Comparative 3D Structure on Q53ET0
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0008140 cAMP response element binding protein binding

Biological Process:
GO:0006094 gluconeogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0016032 viral process
GO:0032793 positive regulation of CREB transcription factor activity
GO:0042593 glucose homeostasis
GO:0043970 histone H3-K9 acetylation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051289 protein homotetramerization
GO:1901998 toxin transport

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0070062 extracellular exosome

-  Descriptions from all associated GenBank mRNAs
  LF206196 - JP 2014500723-A/13699: Polycomb-Associated Non-Coding RNAs.
BC028886 - Homo sapiens CREB regulated transcription coactivator 2, mRNA (cDNA clone IMAGE:4500140), partial cds.
BC033304 - Homo sapiens CREB regulated transcription coactivator 2, mRNA (cDNA clone IMAGE:4933098).
BC053562 - Homo sapiens CREB regulated transcription coactivator 2, mRNA (cDNA clone MGC:61711 IMAGE:6188068), complete cds.
AF289574 - Homo sapiens clone pp6933 unknown mRNA.
BC086958 - Homo sapiens cDNA clone IMAGE:5210435, **** WARNING: chimeric clone ****.
AK096382 - Homo sapiens cDNA FLJ39063 fis, clone NT2RP7014348, highly similar to Homo sapiens transducer of regulated cAMP response element-binding protein (CREB) 2 (TORC2), mRNA.
JD375888 - Sequence 356912 from Patent EP1572962.
JD403057 - Sequence 384081 from Patent EP1572962.
JD253748 - Sequence 234772 from Patent EP1572962.
LF352372 - JP 2014500723-A/159875: Polycomb-Associated Non-Coding RNAs.
AY726597 - Homo sapiens clone MO-27 mRNA sequence.
JD383514 - Sequence 364538 from Patent EP1572962.
JD484010 - Sequence 465034 from Patent EP1572962.
JD445855 - Sequence 426879 from Patent EP1572962.
LF352371 - JP 2014500723-A/159874: Polycomb-Associated Non-Coding RNAs.
JD511960 - Sequence 492984 from Patent EP1572962.
JD547047 - Sequence 528071 from Patent EP1572962.
JD276253 - Sequence 257277 from Patent EP1572962.
JD450350 - Sequence 431374 from Patent EP1572962.
AY360172 - Homo sapiens transducer of regulated CREB protein 2 (TORC2) mRNA, complete cds.
LF352370 - JP 2014500723-A/159873: Polycomb-Associated Non-Coding RNAs.
AK223559 - Homo sapiens mRNA for hypothetical protein LOC200186 variant, clone: FCC127E09.
JD398145 - Sequence 379169 from Patent EP1572962.
JD113526 - Sequence 94550 from Patent EP1572962.
JD115435 - Sequence 96459 from Patent EP1572962.
JD121502 - Sequence 102526 from Patent EP1572962.
JD121501 - Sequence 102525 from Patent EP1572962.
JD210230 - Sequence 191254 from Patent EP1572962.
KJ900410 - Synthetic construct Homo sapiens clone ccsbBroadEn_09804 CRTC2 gene, encodes complete protein.
LF352369 - JP 2014500723-A/159872: Polycomb-Associated Non-Coding RNAs.
LF352368 - JP 2014500723-A/159871: Polycomb-Associated Non-Coding RNAs.
LF352367 - JP 2014500723-A/159870: Polycomb-Associated Non-Coding RNAs.
JD173582 - Sequence 154606 from Patent EP1572962.
JD224761 - Sequence 205785 from Patent EP1572962.
JD216813 - Sequence 197837 from Patent EP1572962.
JD178234 - Sequence 159258 from Patent EP1572962.
MA587949 - JP 2018138019-A/159875: Polycomb-Associated Non-Coding RNAs.
MA587948 - JP 2018138019-A/159874: Polycomb-Associated Non-Coding RNAs.
MA587947 - JP 2018138019-A/159873: Polycomb-Associated Non-Coding RNAs.
MA587946 - JP 2018138019-A/159872: Polycomb-Associated Non-Coding RNAs.
MA587945 - JP 2018138019-A/159871: Polycomb-Associated Non-Coding RNAs.
MA587944 - JP 2018138019-A/159870: Polycomb-Associated Non-Coding RNAs.
MA441773 - JP 2018138019-A/13699: Polycomb-Associated Non-Coding RNAs.

-  Other Names for This Gene
  Alternate Gene Symbols: CRTC2_HUMAN, NM_181715, NP_859066, Q53ET0, Q6UUV8, Q7Z3X7, TORC2
UCSC ID: uc021pab.1
RefSeq Accession: NM_181715
Protein: Q53ET0 (aka CRTC2_HUMAN)
CCDS: CCDS30875.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_181715.2
exon count: 14CDS single in 3' UTR: no RNA size: 2696
ORF size: 2082CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4361.00frame shift in genome: no % Coverage: 99.26
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 1
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.