CRTC2_RAT
ID CRTC2_RAT Reviewed; 691 AA.
AC Q3LRZ1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=CREB-regulated transcription coactivator 2;
DE AltName: Full=Transducer of regulated cAMP response element-binding protein 2;
DE Short=TORC-2;
DE Short=Transducer of CREB protein 2;
GN Name=Crtc2; Synonyms=Torc2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Wu H., Miao S., Shen H., Xiong Z.;
RT "TORC2 in central nervous system.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-611, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcriptional coactivator for CREB1 which activates
CC transcription through both consensus and variant cAMP response element
CC (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway,
CC being active when dephosphorylated and acts independently of CREB1
CC 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4.
CC Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2
CC signaling pathway. Regulates the expression of specific genes such as
CC the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and
CC inducer of mitochondrial biogenesis in muscle cells (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Binds, as a tetramer, through its N-terminal region, with the
CC bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is
CC essential for this interaction. Interaction, via its C-terminal, with
CC TAF4, enhances recruitment of TAF4 to CREB1. Interacts with SIK2.
CC Interacts with 14-3-3 proteins, YWHAB and YWHAG. Interacts (probably
CC when phosphorylated at Ser-171) with YWHAE. Interacts with calmodulin-
CC dependent catalytic subunit PPP3CA/calcineurin A (By similarity).
CC Interaction with COP1 mediates nuclear export and degradation of CRTC2
CC (By similarity). {ECO:0000250|UniProtKB:Q3U182,
CC ECO:0000250|UniProtKB:Q53ET0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q53ET0}. Nucleus
CC {ECO:0000250|UniProtKB:Q53ET0}. Note=Translocated from the nucleus to
CC the cytoplasm on interaction of the phosphorylated form with 14-3-3
CC protein. In response to cAMP levels and glucagon, relocated to the
CC nucleus. {ECO:0000250|UniProtKB:Q53ET0}.
CC -!- PTM: Phosphorylation/dephosphorylation states of Ser-171 are required
CC for regulating transduction of CREB activity. CRTCs/TORCs are inactive
CC when phosphorylated, and active when dephosphorylated at this site.
CC This primary site of phosphorylation, is regulated by cAMP and calcium
CC levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2)
CC by LKB1 (By similarity). Following adenylyl cyclase activation,
CC dephosphorylated at Ser-171 by PPP3CA/calcineurin A resulting in CRTC2
CC dissociation from 14-3-3 proteins and PPP3CA (By similarity). Both
CC insulin and AMPK increase this phosphorylation of CRTC2 while glucagon
CC suppresses it. Phosphorylation at Ser-274 by MARK2 is induced under low
CC glucose conditions and dephosphorylated in response to glucose influx.
CC Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins
CC and translocation to the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:Q3U182, ECO:0000250|UniProtKB:Q53ET0}.
CC -!- PTM: Asymmetric dimethylation of arginine resisues by PRMT6 enhances
CC the association of CRTC2 with CREB on the promoters of gluconeogenic
CC genes. {ECO:0000250|UniProtKB:Q3U182}.
CC -!- SIMILARITY: Belongs to the TORC family. {ECO:0000305}.
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DR EMBL; DQ185515; ABA28301.1; -; mRNA.
DR RefSeq; NP_001029067.1; NM_001033895.1.
DR AlphaFoldDB; Q3LRZ1; -.
DR SMR; Q3LRZ1; -.
DR BioGRID; 259674; 3.
DR STRING; 10116.ENSRNOP00000021700; -.
DR iPTMnet; Q3LRZ1; -.
DR PhosphoSitePlus; Q3LRZ1; -.
DR jPOST; Q3LRZ1; -.
DR PaxDb; Q3LRZ1; -.
DR PRIDE; Q3LRZ1; -.
DR GeneID; 310615; -.
DR KEGG; rno:310615; -.
DR UCSC; RGD:1308903; rat.
DR CTD; 200186; -.
DR RGD; 1308903; Crtc2.
DR VEuPathDB; HostDB:ENSRNOG00000056337; -.
DR eggNOG; ENOG502QVWA; Eukaryota.
DR HOGENOM; CLU_019357_1_0_1; -.
DR InParanoid; Q3LRZ1; -.
DR OMA; YPRHIID; -.
DR OrthoDB; 1118500at2759; -.
DR PhylomeDB; Q3LRZ1; -.
DR PRO; PR:Q3LRZ1; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000056337; Expressed in spleen and 20 other tissues.
DR ExpressionAtlas; Q3LRZ1; baseline and differential.
DR Genevisible; Q3LRZ1; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:RGD.
DR GO; GO:0043970; P:histone H3-K9 acetylation; ISO:RGD.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:1901998; P:toxin transport; ISO:RGD.
DR InterPro; IPR024786; TORC.
DR InterPro; IPR024785; TORC_C.
DR InterPro; IPR024784; TORC_M.
DR InterPro; IPR024783; TORC_N.
DR PANTHER; PTHR13589; PTHR13589; 1.
DR Pfam; PF12886; TORC_C; 1.
DR Pfam; PF12885; TORC_M; 1.
DR Pfam; PF12884; TORC_N; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Cytoplasm; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT CHAIN 2..691
FT /note="CREB-regulated transcription coactivator 2"
FT /id="PRO_0000318530"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 513..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 271..287
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 627
FT /note="Required for ubiquitination and degradation"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 51
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 99
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 120
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 123
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 161
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 168
FT /note="Asymmetric dimethylarginine; by PRMT6"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 169
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 171
FT /note="Phosphoserine; by AMPK, MARK2, SIK1 and SIK2"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 192
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 274
FT /note="Phosphoserine; by MARK2"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 488
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 489
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 501
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3U182"
FT MOD_RES 622
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
SQ SEQUENCE 691 AA; 73146 MW; 8CC1DA5B06D890B0 CRC64;
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST RLQAQKLRLA
YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH HGLVERVQRD PRRMVSPLRR
YPRHIDSSPY SPAYLSPPPE SGWRRMMPWG NLPAEKGQLF RLPSALNRTS SDSALHTSVM
NPNPQDTYPG PTPPSVLPSR RGGFLDGEMD AKVPAIEENL VDDKHLLKPW DAKKLSSSSS
RPRSCEVPGI NIFPSPDQPA NVPVLPPAMS TGGSLPDLTN LHFPPPLPTP LDPEETVYPS
LSGGNSTTNL THTMTHLGIS GGLGLGPSYD VPGLHSPLSH PSLQSSLSNP NLQASLSSPQ
PQLQGSHSHP SLPASSLAHH ALPTTSLGHP SLSAPALSSS SSSSSTSSPV LSAPPYPAST
PGASPRHRRV PLSPLSLPAG PADARRSQQQ LPKQFSPTMS PTLSSITQGV PLDTSKLPTD
QRLPPYPYSP PSLVIPSHPP TPKSLQQLPS QACLVQPSGG QPPGRQPHYG TLYPPGSSGH
GQQPYHRPIN DFSLGNLEQF NMESPSTSLV LDPPAFSEGP GFLGSEGSVS GPQDSHVLNH
QNLTHCSRHG SGPNIILTGD SSPGFSKEIA AALAGVPGFE VSASGLELGL GLEDELRMEP
LGLEGLTMLS DPCALLPDPA VEDSFRSDRL Q
