CRTC2_BOVIN
ID CRTC2_BOVIN Reviewed; 693 AA.
AC Q08E26;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 87.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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|UniProtKB:Q53ET0}.
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; BC123454; AAI23455.1; -; mRNA.
DR RefSeq; NP_001069718.1; NM_001076250.1.
DR AlphaFoldDB; Q08E26; -.
DR SMR; Q08E26; -.
DR STRING; 9913.ENSBTAP00000050880; -.
DR PaxDb; Q08E26; -.
DR PeptideAtlas; Q08E26; -.
DR PRIDE; Q08E26; -.
DR Ensembl; ENSBTAT00000056382; ENSBTAP00000050880; ENSBTAG00000017942.
DR GeneID; 540959; -.
DR KEGG; bta:540959; -.
DR CTD; 200186; -.
DR VEuPathDB; HostDB:ENSBTAG00000017942; -.
DR VGNC; VGNC:97256; CRTC2.
DR eggNOG; ENOG502QVWA; Eukaryota.
DR GeneTree; ENSGT00390000010652; -.
DR HOGENOM; CLU_019357_1_0_1; -.
DR InParanoid; Q08E26; -.
DR OMA; YPRHIID; -.
DR OrthoDB; 1118500at2759; -.
DR TreeFam; TF321571; -.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000017942; Expressed in urinary bladder and 105 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
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 2: Evidence at transcript 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..693
FT /note="CREB-regulated transcription coactivator 2"
FT /id="PRO_0000318527"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 174..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..215
FT /note="Required for interaction with COP1"
FT /evidence="ECO:0000250"
FT REGION 271..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..548
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 174..192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..463
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..507
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 629
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"
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 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53ET0"
FT MOD_RES 624
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 693 AA; 72818 MW; 497F16B29F62C135 CRC64;
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST RLQAQKLRLA
YTRSSHYGGS LPNVNQIGCG LAEFQSPLHS PLDSSRSTRH HGLVERVQRD PRRMVSPLRR
YARHIDSSPY SPAYLSPPPE SSWRRTMPWG SFPAEKGQLF RLPSALNRTS SDSALHTSVM
NPSPQDTYPS PAAPSVLPSR RGGCLDGETD SKVPAIEENL LDDKHLLKPW DAKKLSSSSS
RPRSCEVPGI NIFPSPDQPA TVPVLPPAMN TGGSLPDLTN LHFPPPLPTP LDPEETAYPS
LSGGSSTSNL THTMTHLGIS GGLALGPGYD APGLHSPLSH PSFQSSLSNP NLQASLSSPQ
PQLQGSHSHP SLPASSLARH ALPTTSLGHP SLSAPALSSS SSSSSASSPV LGAPAYPASA
PGASPRHRRV PLSPLSLPAG PADARRSQQQ LPKQFSPTMS PTLSSITQGV ALDTSKLPTD
QRLPPYPYSP PSLVLPTQQP TPKPLQQPGL PSQACSVQPS GGQPPGRQLQ YGTLYPPGPS
GHGQQSYHRS MSDFSLGNLE QFNMENPSTS LALDPPGFSE GPGFLGGEGP VSGPQDPHAL
NHQNVTHCSR HGSGPNVILT GDASPGFSKE IAAALAGVPG FEVSAAGLGL GLGLEEELRM
EPLGLEGLSM LSDPCALLPD PAVEDSFRSD RLQ
