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Q3U182 (CRTC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Crtc2
Synonyms:Torc2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length692 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Ref.3 Ref.4

Subunit structure

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. Ref.5

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. Ref.3 Ref.4 Ref.5

Post-translational modification

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-274 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-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm By similarity. Ref.3 Ref.4 Ref.5

Sequence similarities

Belongs to the TORC family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 692691CREB-regulated transcription coactivator 2
PRO_0000318529

Regions

Region209 – 2157Required for interaction with RFWD2/COP1
Region272 – 28817Nuclear export signal By similarity
Compositional bias237 – 2415Poly-Ser
Compositional bias337 – 41377Ser-rich

Sites

Site6281Required for ubiquitination and degradation

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue701Phosphoserine By similarity
Modified residue861Phosphoserine By similarity
Modified residue901Phosphoserine By similarity
Modified residue1361Phosphoserine By similarity
Modified residue1711Phosphoserine; by AMPK, MARK2, SIK1 and SIK2 Ref.3 Ref.4 Ref.5
Modified residue1921Phosphothreonine By similarity
Modified residue2751Phosphoserine; by MARK2 By similarity
Modified residue3071Phosphoserine By similarity
Modified residue3691Phosphoserine By similarity
Modified residue3941Phosphoserine By similarity
Modified residue4341Phosphoserine By similarity
Modified residue4571Phosphoserine By similarity
Modified residue4891Phosphotyrosine
Modified residue4901Phosphoserine By similarity
Modified residue4931Phosphoserine By similarity
Modified residue5021Phosphothreonine By similarity
Modified residue6121Phosphoserine Ref.6
Modified residue6231Phosphoserine By similarity

Experimental info

Mutagenesis1711S → A: Upregulates CREB-mediated gluconeogenic gene expression. No degradation of CRTC2. Loss of SIK2-mediated phosphorylation. Ref.5
Mutagenesis2131K → R: No effect on COP1-mediated degradation of TORC1 under forksolin stimulation.
Mutagenesis2141V → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. Ref.5
Mutagenesis2151P → A: No interaction with RFWD2/COP1. Inhibition of degradation under exposure to FSK/INS. Ref.5
Mutagenesis6281K → R: Translocates to the nucleus and no COP1-mediated degradation. Ref.5
Sequence conflict1951S → G in BAE33618. Ref.1
Sequence conflict2031G → R in BAE42818. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q3U182 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: 5BCBC416D45CFAD8

FASTA69273,216
        10         20         30         40         50         60 
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST RLQAQKLRLA 

        70         80         90        100        110        120 
YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH HGLVERVQRD ARRMVSPLRR 

       130        140        150        160        170        180 
YPRHIDSSPY SPAYLSPPPE SGWRRMMPWG NLPAEKGQLF RLPSALNRTS SDSALHTSVM 

       190        200        210        220        230        240 
NPNPQDTYPG PTPPSVLPSR RGGGFLDGEM DAKVPAIEEN VVDDKHLLKP WDAKKLSSSS 

       250        260        270        280        290        300 
SRPRSCEVPG INIFPSPDQP ANVPVLPPAM NTGGSLPDLT NLHFPPPLPT PLDPEETVYP 

       310        320        330        340        350        360 
SLSGGNSTTN LTHTMTHLGI SGGLGLGPSY DVPGLHSPLS HPSLQSSLSN PNLQASLSSP 

       370        380        390        400        410        420 
QPQLQGSHSH PSLPASSLAH HALPTTSLGH PSLSAPALSS SSSSSSTSSP VLSAPPYPAS 

       430        440        450        460        470        480 
TPGASPRHRR VPLSPLSLPA GPADARRSQQ QLPKQFSPTM SPTLSSITQG VPLDTSKLPT 

       490        500        510        520        530        540 
DQRLPPYPYS PPSLVIPTHP PTPKSLQQLP SQACLVQPSG GQPPGRQPHY GALYPPGSSG 

       550        560        570        580        590        600 
HGQQPYHRPI NDFSLGNLEQ FNMESPSTSL VLDPPAFSEG PGFLGSEGSM SGPQDPHVLN 

       610        620        630        640        650        660 
HQNLTHCSRH GSGPNIILTG DSSPGFSKEI AAALAGVPGF EVSASGLELG LGLEDELRME 

       670        680        690 
PLGLEGLTML SDPCALLPDP AVEDSFRSDR LQ 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism."
Koo S.-H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S., Hedrick S., Xu W., Boussouar F., Brindle P., Takemori H., Montminy M.
Nature 437:1109-1111(2005) [PubMed] [Europe PMC] [Abstract]
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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_083157.1. NM_028881.2.
UniGeneMm.35627.

3D structure databases

ProteinModelPortalQ3U182.
SMRQ3U182. Positions 20-47.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-46162N.
IntActQ3U182. 1 interaction.

Proteomic databases

PaxDbQ3U182.
PRIDEQ3U182.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029545; ENSMUSP00000029545; ENSMUSG00000027936.
GeneID74343.
KEGGmmu:74343.
UCSCuc008qbt.2. mouse.

Organism-specific databases

CTD200186.
MGIMGI:1921593. Crtc2.

Phylogenomic databases

eggNOGNOG74259.
GeneTreeENSGT00390000010652.
HOGENOMHOG000111980.
HOVERGENHBG058314.
InParanoidQ3U182.
KOK16333.
OMATHCSRHG.
OrthoDBEOG7MKW5P.
PhylomeDBQ3U182.
TreeFamTF321571.

Gene expression databases

ArrayExpressQ3U182.
BgeeQ3U182.
CleanExMM_CRTC2.
GenevestigatorQ3U182.

Family and domain databases

InterProIPR024786. TORC.
IPR024785. TORC_C.
IPR024784. TORC_M.
IPR024783. TORC_N.
[Graphical view]
PANTHERPTHR13589. PTHR13589. 1 hit.
PfamPF12886. TORC_C. 1 hit.
PF12885. TORC_M. 1 hit.
PF12884. TORC_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio340497.
PROQ3U182.
SOURCESearch...

Entry information

Entry nameCRTC2_MOUSE
AccessionPrimary (citable) accession number: Q3U182
Secondary accession number(s): Q3TA52, Q8BH09
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot