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Q3U182

- CRTC2_MOUSE

UniProt

Q3U182 - CRTC2_MOUSE

Protein

CREB-regulated transcription coactivator 2

Gene

Crtc2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 74 (01 Oct 2014)
      Sequence version 2 (05 Feb 2008)
      Previous versions | rss
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    Functioni

    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 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei628 – 6281Required for ubiquitination and degradation

    GO - Molecular functioni

    1. cAMP response element binding protein binding Source: InterPro
    2. protein binding Source: MGI

    GO - Biological processi

    1. gluconeogenesis Source: UniProtKB
    2. glucose homeostasis Source: UniProtKB
    3. histone H3-K9 acetylation Source: MGI
    4. positive regulation of CREB transcription factor activity Source: UniProtKB
    5. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    6. protein homotetramerization Source: InterPro
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CREB-regulated transcription coactivator 2
    Alternative name(s):
    Transducer of regulated cAMP response element-binding protein 2
    Short name:
    TORC-2
    Short name:
    Transducer of CREB protein 2
    Gene namesi
    Name:Crtc2
    Synonyms:Torc2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:1921593. Crtc2.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi171 – 1711S → A: Upregulates CREB-mediated gluconeogenic gene expression. No degradation of CRTC2. Loss of SIK2-mediated phosphorylation. 1 Publication
    Mutagenesisi213 – 2131K → R: No effect on COP1-mediated degradation of TORC1 under forksolin stimulation.
    Mutagenesisi214 – 2141V → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication
    Mutagenesisi215 – 2151P → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. 1 Publication
    Mutagenesisi628 – 6281K → R: Translocates to the nucleus and no COP1-mediated degradation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 692691CREB-regulated transcription coactivator 2PRO_0000318529Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei51 – 511Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei70 – 701PhosphoserineBy similarity
    Modified residuei86 – 861PhosphoserineBy similarity
    Modified residuei90 – 901PhosphoserineBy similarity
    Modified residuei99 – 991Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei120 – 1201Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei123 – 1231Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei136 – 1361PhosphoserineBy similarity
    Modified residuei161 – 1611Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei168 – 1681Asymmetric dimethylarginine; by PRMT61 Publication
    Modified residuei171 – 1711Phosphoserine; by AMPK, MARK2, SIK1 and SIK23 Publications
    Modified residuei192 – 1921PhosphothreonineBy similarity
    Modified residuei275 – 2751Phosphoserine; by MARK2By similarity
    Modified residuei307 – 3071PhosphoserineBy similarity
    Modified residuei369 – 3691PhosphoserineBy similarity
    Modified residuei394 – 3941PhosphoserineBy similarity
    Modified residuei434 – 4341PhosphoserineBy similarity
    Modified residuei457 – 4571PhosphoserineBy similarity
    Modified residuei489 – 4891Phosphotyrosine
    Modified residuei490 – 4901PhosphoserineBy similarity
    Modified residuei493 – 4931PhosphoserineBy similarity
    Modified residuei502 – 5021PhosphothreonineBy similarity
    Modified residuei612 – 6121Phosphoserine1 Publication
    Modified residuei623 – 6231PhosphoserineBy similarity

    Post-translational modificationi

    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. Phosphorylation at Ser-275 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx. Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it. Phosphorylation at Ser-275 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm By similarity.By similarity
    Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ3U182.
    PaxDbiQ3U182.
    PRIDEiQ3U182.

    Expressioni

    Gene expression databases

    ArrayExpressiQ3U182.
    BgeeiQ3U182.
    CleanExiMM_CRTC2.
    GenevestigatoriQ3U182.

    Interactioni

    Subunit structurei

    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 By similarity. Interaction with RFWD2/COP1 mediates nuclear export and degradation of CRTC2.By similarity1 Publication

    Protein-protein interaction databases

    DIPiDIP-46162N.
    IntActiQ3U182. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ3U182.
    SMRiQ3U182. Positions 20-47.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni209 – 2157Required for interaction with RFWD2/COP1
    Regioni272 – 28817Nuclear export signalBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi237 – 2415Poly-Ser
    Compositional biasi337 – 41377Ser-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the TORC family.Curated

    Phylogenomic databases

    eggNOGiNOG74259.
    GeneTreeiENSGT00390000010652.
    HOGENOMiHOG000111980.
    HOVERGENiHBG058314.
    InParanoidiQ3U182.
    KOiK16333.
    OMAiTHCSRHG.
    OrthoDBiEOG7MKW5P.
    PhylomeDBiQ3U182.
    TreeFamiTF321571.

    Family and domain databases

    InterProiIPR024786. TORC.
    IPR024785. TORC_C.
    IPR024784. TORC_M.
    IPR024783. TORC_N.
    [Graphical view]
    PANTHERiPTHR13589. PTHR13589. 1 hit.
    PfamiPF12886. TORC_C. 1 hit.
    PF12885. TORC_M. 1 hit.
    PF12884. TORC_N. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q3U182-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST    50
    RLQAQKLRLA YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH 100
    HGLVERVQRD ARRMVSPLRR YPRHIDSSPY SPAYLSPPPE SGWRRMMPWG 150
    NLPAEKGQLF RLPSALNRTS SDSALHTSVM NPNPQDTYPG PTPPSVLPSR 200
    RGGGFLDGEM DAKVPAIEEN VVDDKHLLKP WDAKKLSSSS SRPRSCEVPG 250
    INIFPSPDQP ANVPVLPPAM NTGGSLPDLT NLHFPPPLPT PLDPEETVYP 300
    SLSGGNSTTN LTHTMTHLGI SGGLGLGPSY DVPGLHSPLS HPSLQSSLSN 350
    PNLQASLSSP QPQLQGSHSH PSLPASSLAH HALPTTSLGH PSLSAPALSS 400
    SSSSSSTSSP VLSAPPYPAS TPGASPRHRR VPLSPLSLPA GPADARRSQQ 450
    QLPKQFSPTM SPTLSSITQG VPLDTSKLPT DQRLPPYPYS PPSLVIPTHP 500
    PTPKSLQQLP SQACLVQPSG GQPPGRQPHY GALYPPGSSG HGQQPYHRPI 550
    NDFSLGNLEQ FNMESPSTSL VLDPPAFSEG PGFLGSEGSM SGPQDPHVLN 600
    HQNLTHCSRH GSGPNIILTG DSSPGFSKEI AAALAGVPGF EVSASGLELG 650
    LGLEDELRME PLGLEGLTML SDPCALLPDP AVEDSFRSDR LQ 692
    Length:692
    Mass (Da):73,216
    Last modified:February 5, 2008 - v2
    Checksum:i5BCBC416D45CFAD8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti195 – 1951S → G in BAE33618. (PubMed:16141072)Curated
    Sequence conflicti203 – 2031G → R in BAE42818. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK156192 mRNA. Translation: BAE33618.1.
    AK172084 mRNA. Translation: BAE42818.1.
    BC023831 mRNA. Translation: AAH23831.1.
    BC032183 mRNA. Translation: AAH32183.1.
    BC033300 mRNA. Translation: AAH33300.1.
    CCDSiCCDS38501.1.
    RefSeqiNP_083157.1. NM_028881.2.
    UniGeneiMm.35627.

    Genome annotation databases

    EnsembliENSMUST00000029545; ENSMUSP00000029545; ENSMUSG00000027936.
    GeneIDi74343.
    KEGGimmu:74343.
    UCSCiuc008qbt.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK156192 mRNA. Translation: BAE33618.1 .
    AK172084 mRNA. Translation: BAE42818.1 .
    BC023831 mRNA. Translation: AAH23831.1 .
    BC032183 mRNA. Translation: AAH32183.1 .
    BC033300 mRNA. Translation: AAH33300.1 .
    CCDSi CCDS38501.1.
    RefSeqi NP_083157.1. NM_028881.2.
    UniGenei Mm.35627.

    3D structure databases

    ProteinModelPortali Q3U182.
    SMRi Q3U182. Positions 20-47.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-46162N.
    IntActi Q3U182. 1 interaction.

    Proteomic databases

    MaxQBi Q3U182.
    PaxDbi Q3U182.
    PRIDEi Q3U182.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000029545 ; ENSMUSP00000029545 ; ENSMUSG00000027936 .
    GeneIDi 74343.
    KEGGi mmu:74343.
    UCSCi uc008qbt.2. mouse.

    Organism-specific databases

    CTDi 200186.
    MGIi MGI:1921593. Crtc2.

    Phylogenomic databases

    eggNOGi NOG74259.
    GeneTreei ENSGT00390000010652.
    HOGENOMi HOG000111980.
    HOVERGENi HBG058314.
    InParanoidi Q3U182.
    KOi K16333.
    OMAi THCSRHG.
    OrthoDBi EOG7MKW5P.
    PhylomeDBi Q3U182.
    TreeFami TF321571.

    Miscellaneous databases

    NextBioi 340497.
    PROi Q3U182.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q3U182.
    Bgeei Q3U182.
    CleanExi MM_CRTC2.
    Genevestigatori Q3U182.

    Family and domain databases

    InterProi IPR024786. TORC.
    IPR024785. TORC_C.
    IPR024784. TORC_M.
    IPR024783. TORC_N.
    [Graphical view ]
    PANTHERi PTHR13589. PTHR13589. 1 hit.
    Pfami PF12886. TORC_C. 1 hit.
    PF12885. TORC_M. 1 hit.
    PF12884. TORC_N. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: NOD.
      Tissue: Spleen.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Liver, Mammary tumor and Salivary gland.
    3. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-171, TISSUE SPECIFICITY.
    4. "The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin."
      Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N., Depinho R.A., Montminy M., Cantley L.C.
      Science 310:1642-1646(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT SER-171, SUBCELLULAR LOCATION.
    5. "Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2."
      Dentin R., Liu Y., Koo S.-H., Hedrick S., Vargas T., Heredia J., Yates J. III, Montminy M.
      Nature 449:366-369(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RFWD2, PHOSPHORYLATION AT SER-171, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-171; VAL-214; PRO-215 AND LYS-628.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    7. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism."
      Han H.S., Jung C.Y., Yoon Y.S., Choi S., Choi D., Kang G., Park K.G., Kim S.T., Koo S.H.
      Sci. Signal. 7:RA19-RA19(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: METHYLATION AT ARG-51; ARG-99; ARG-120; ARG-123; ARG-161 AND ARG-168.

    Entry informationi

    Entry nameiCRTC2_MOUSE
    AccessioniPrimary (citable) accession number: Q3U182
    Secondary accession number(s): Q3TA52, Q8BH09
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 5, 2008
    Last sequence update: February 5, 2008
    Last modified: October 1, 2014
    This is version 74 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3