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    CRTC2 CREB regulated transcription coactivator 2 [ Homo sapiens (human) ]

    Gene ID: 200186, updated on 27-Nov-2024

    Summary

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    Official Symbol
    CRTC2provided by HGNC
    Official Full Name
    CREB regulated transcription coactivator 2provided by HGNC
    Primary source
    HGNC:HGNC:27301
    See related
    Ensembl:ENSG00000160741 MIM:608972; AllianceGenome:HGNC:27301
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TORC2; TORC-2
    Summary
    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]
    Expression
    Ubiquitous expression in spleen (RPKM 17.9), bone marrow (RPKM 17.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CRTC2 in Genome Data Viewer
    Location:
    1q21.3
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (153947675..153958612, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (153084936..153095873, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (153920151..153931088, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene GATA zinc finger domain containing 2B Neighboring gene adipose differentiation-related protein pseudogene Neighboring gene Sharpr-MPRA regulatory region 14566 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:153877149-153877650 Neighboring gene Sharpr-MPRA regulatory region 2699 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1345 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1755 Neighboring gene uncharacterized LOC101928059 Neighboring gene Sharpr-MPRA regulatory region 4321 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:153897582-153897755 Neighboring gene DENN domain containing 4B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1756 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1757 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:153918384-153918884 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1758 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1759 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1760 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1761 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1347 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1762 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:153935601-153936800 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:153939664-153940520 Neighboring gene solute carrier family 39 member 1 Neighboring gene microRNA 6737 Neighboring gene cAMP responsive element binding protein 3 like 4 Neighboring gene jumping translocation breakpoint

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Inactivation of Cyclic AMP Response Element Transcription Caused by Constitutive p38 Activation Is Mediated by Hyperphosphorylation-Dependent CRTC2 Nucleocytoplasmic Transport. Ma H, et al. Mol Cell Biol, 2019 May 1. PMID 30782776, Free PMC Article
    2. Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Brown KA, et al. Cancer Res, 2009 Jul 1. PMID 19509226
    3. The induction of IL-10 by zymosan in dendritic cells depends on CREB activation by the coactivators CREB-binding protein and TORC2 and autocrine PGE2. Alvarez Y, et al. J Immunol, 2009 Jul 15. PMID 19564345
    4. The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR. Ma L, et al. Virol Sin, 2021 Aug. PMID 33723808, Free PMC Article
    5. CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis. Hill MJ, et al. Mol Endocrinol, 2016 Jan. PMID 26652733, Free PMC Article

    See all (89) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. cAMP-Induced Nuclear Condensation of CRTC2 Promotes Transcription Elongation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease.
      Title: cAMP-Induced Nuclear Condensation of CRTC2 Promotes Transcription Elongation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease.
    2. Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer.
      Title: Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer.
    3. TORC2/3-mediated DUSP1 upregulation is essential for human decidualization.
      Title: TORC2/3-mediated DUSP1 upregulation is essential for human decidualization.
    4. Phosphorylation of CREB-Specific Coactivator CRTC2 at Ser238 Promotes Proliferation, Migration, and Invasion of Colorectal Cancer Cells.
      Title: Phosphorylation of CREB-Specific Coactivator CRTC2 at Ser238 Promotes Proliferation, Migration, and Invasion of Colorectal Cancer Cells.
    5. The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR.
      Title: The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA Pol II from Binding to HIV-1 LTR.
    6. Sam68 promotes hepatic gluconeogenesis via CRTC2.
      Title: Sam68 promotes hepatic gluconeogenesis via CRTC2.
    7. SIK1 Regulates CRTC2-Mediated Gluconeogenesis Signaling Pathway in Human and Mouse Liver Cells.
      Title: SIK1 Regulates CRTC2-Mediated Gluconeogenesis Signaling Pathway in Human and Mouse Liver Cells.
    8. CRTC2 is unphosphorylated and therefore constitutively activated in LKB1-mutant non-small cell lung cance, where it promotes tumor growth, in part via the induction of the inhibitor of DNA binding 1.
      Title: The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non-small cell lung cancer.
    9. Results identified CRTC2 as a downstream substrate of constitutively activated p38. Constitutive, rather than transient, activation of p38 led to hyperphosphorylation of CRTC2, resulting in CRTC2 cytosolic relocation and subsequent inactivation of cyclic AMP response element (CRE)-mediated transcription.
      Title: Inactivation of Cyclic AMP Response Element Transcription Caused by Constitutive p38 Activation Is Mediated by Hyperphosphorylation-Dependent CRTC2 Nucleocytoplasmic Transport.
    10. Data report crystal structures of a complex containing the CRTC2 CREB binding domain, the CREB basic leucine zipper domain and a CRE-containing DNA. The structures revealed that CRTC and CREB form a 2:2 complex on CRE-containing DNA, and CRTC interacts with both CREB and DNA through highly conserved residues.
      Title: Structural Insights into the CRTC2-CREB Complex Assembly on CRE.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of CREB regulated transcription coactivator 2 (CRTC2) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cAMP response element binding protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cellular response to cAMP IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in gluconeogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in glucose homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of CREB transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein homotetramerization IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    CREB-regulated transcription coactivator 2
    Names
    transducer of regulated cAMP response element-binding protein (CREB) 2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_181715.3 → NP_859066.1  CREB-regulated transcription coactivator 2

      See identical proteins and their annotated locations for NP_859066.1

      Status: REVIEWED

      Source sequence(s)
      AY360172, AY726597, BC053562, BM987537
      Consensus CDS
      CCDS30875.1
      UniProtKB/Swiss-Prot
      Q53ET0, Q6UUV8, Q7Z3X7, Q8N332
      Related
      ENSP00000357622.1, ENST00000368633.2
      Conserved Domains (3) summary
      pfam12884
      Location:18 → 72
      TORC_N; Transducer of regulated CREB activity, N terminus
      pfam12885
      Location:168 → 320
      TORC_M; Transducer of regulated CREB activity middle domain
      pfam12886
      Location:615 → 692
      TORC_C; Transducer of regulated CREB activity, C terminus

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      153947675..153958612 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017000577.2 → XP_016856066.1  CREB-regulated transcription coactivator 2 isoform X4

    2. XM_005244946.2 → XP_005245003.1  CREB-regulated transcription coactivator 2 isoform X1

      Related
      ENST00000487235.5
      Conserved Domains (3) summary
      pfam12884
      Location:18 → 72
      TORC_N; Transducer of regulated CREB activity, N terminus
      pfam12885
      Location:168 → 325
      TORC_M; Transducer of regulated CREB activity middle domain
      pfam12886
      Location:620 → 697
      TORC_C; Transducer of regulated CREB activity, C terminus

    3. XM_017000576.1 → XP_016856065.1  CREB-regulated transcription coactivator 2 isoform X3

    4. XM_017000575.1 → XP_016856064.1  CREB-regulated transcription coactivator 2 isoform X2

    5. XM_017000579.2 → XP_016856068.1  CREB-regulated transcription coactivator 2 isoform X5

    6. XM_047448820.1 → XP_047304776.1  CREB-regulated transcription coactivator 2 isoform X6

    7. XM_047448823.1 → XP_047304779.1  CREB-regulated transcription coactivator 2 isoform X7

    RNA

    1. XR_007095721.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      153084936..153095873 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334981.1 → XP_054190956.1  CREB-regulated transcription coactivator 2 isoform X4

    2. XM_054334978.1 → XP_054190953.1  CREB-regulated transcription coactivator 2 isoform X1

    3. XM_054334980.1 → XP_054190955.1  CREB-regulated transcription coactivator 2 isoform X3

    4. XM_054334979.1 → XP_054190954.1  CREB-regulated transcription coactivator 2 isoform X2

    5. XM_054334982.1 → XP_054190957.1  CREB-regulated transcription coactivator 2 isoform X5

    6. XM_054334983.1 → XP_054190958.1  CREB-regulated transcription coactivator 2 isoform X6

    7. XM_054334984.1 → XP_054190959.1  CREB-regulated transcription coactivator 2 isoform X7

    RNA

    1. XR_008485960.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q53ET0.2 GenPept UniProtKB/Swiss-Prot:Q53ET0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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