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Protein

CREB-regulated transcription coactivator 2

Gene

CRTC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei629Required for ubiquitination and degradationBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-400253. Circadian Clock.
SIGNORiQ53ET0.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:27301. CRTC2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70S → A: No effect on cAMP- and calcium-regulated phosphorylation. 1
Mutagenesisi171S → A: Loss of cAMP- and calcium-regulated phosphorylation. Greatly reduced interaction with 14-3-3 proteins. Impaired phosphorylation under low glucose conditions and impaired interaction with 14-3-3 proteins; when associated with A-274. 3 Publications1
Mutagenesisi274S → A: Impaired phosphorylation under low glucose conditions and impaired interaction with 14-3-3 proteins; when associated with A-171. 1 Publication1
Mutagenesisi368S → A: Reduced cAMP- and calcium-regulated phosphorylation. 2 Publications1
Mutagenesisi393S → A: No effect on cAMP- and calcium-regulated phosphorylation. 1

Organism-specific databases

DisGeNETi200186.
OpenTargetsiENSG00000160741.
PharmGKBiPA142672073.

Polymorphism and mutation databases

BioMutaiCRTC2.
DMDMi167009135.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00003185282 – 693CREB-regulated transcription coactivator 2Add BLAST692

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei51Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei70PhosphoserineCombined sources1 Publication1
Modified residuei86PhosphoserineCombined sources1
Modified residuei90PhosphoserineCombined sources1 Publication1
Modified residuei99Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei120Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei123Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei136PhosphoserineCombined sources1 Publication1
Modified residuei161Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei168Asymmetric dimethylarginine; by PRMT6By similarity1
Modified residuei171Phosphoserine; by AMPK, MARK2, SIK1 and SIK24 Publications1
Modified residuei192PhosphothreonineCombined sources1
Modified residuei274Phosphoserine; by MARK21 Publication1
Modified residuei306Phosphoserine1 Publication1
Modified residuei368Phosphoserine1 Publication1
Modified residuei393Phosphoserine1 Publication1
Modified residuei433PhosphoserineCombined sources1 Publication1
Modified residuei456Phosphoserine1 Publication1
Modified residuei488PhosphotyrosineCombined sources1
Modified residuei489Phosphoserine1 Publication1
Modified residuei490PhosphoserineCombined sources1
Modified residuei492Phosphoserine1 Publication1
Modified residuei501PhosphothreonineCombined sources1
Modified residuei613PhosphoserineCombined sources1 Publication1
Modified residuei623PhosphoserineBy similarity1
Modified residuei624PhosphoserineCombined sources1

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. Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it. Phosphorylation at Ser-274 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx. Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm.5 Publications
Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ53ET0.
MaxQBiQ53ET0.
PaxDbiQ53ET0.
PeptideAtlasiQ53ET0.
PRIDEiQ53ET0.

PTM databases

iPTMnetiQ53ET0.
PhosphoSitePlusiQ53ET0.

Expressioni

Tissue specificityi

Most abundantly expressed in the thymus. Present in both B and T-lymphocytes. Highly expressed in HEK293T cells and in insulinomas. High levels also in spleen, ovary, muscle and lung, with highest levels in muscle. Lower levels found in brain, colon, heart, kidney, prostate, small intestine and stomach. Weak expression in liver and pancreas.3 Publications

Gene expression databases

BgeeiENSG00000160741.
CleanExiHS_CRTC2.
ExpressionAtlasiQ53ET0. baseline and differential.
GenevisibleiQ53ET0. HS.

Organism-specific databases

HPAiHPA028454.
HPA028465.

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. Interaction with the human T-cell leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal transcription activation by Tax. Interaction with RFWD2/COP1 mediates nuclear export and degradation of CRTC2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
BZLF1P032063EBI-1181987,EBI-2621186From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128308. 24 interactors.
DIPiDIP-29950N.
IntActiQ53ET0. 14 interactors.
MINTiMINT-1631979.
STRINGi9606.ENSP00000357622.

Structurei

Secondary structure

1693
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 45Combined sources25

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HTMX-ray2.00A18-50[»]
ProteinModelPortaliQ53ET0.
SMRiQ53ET0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi271 – 287Nuclear export signalBy similarityAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi236 – 240Poly-Ser5
Compositional biasi336 – 408Ser-richAdd BLAST73

Sequence similaritiesi

Belongs to the TORC family.Curated

Phylogenomic databases

eggNOGiENOG410IGNT. Eukaryota.
ENOG410XPDQ. LUCA.
GeneTreeiENSGT00390000010652.
HOGENOMiHOG000111980.
HOVERGENiHBG058314.
InParanoidiQ53ET0.
KOiK16333.
OMAiHTLNHQN.
OrthoDBiEOG091G03YN.
PhylomeDBiQ53ET0.
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.

Q53ET0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATSGANGPG SATASASNPR KFSEKIALQK QRQAEETAAF EEVMMDIGST
60 70 80 90 100
RLQAQKLRLA YTRSSHYGGS LPNVNQIGSG LAEFQSPLHS PLDSSRSTRH
110 120 130 140 150
HGLVERVQRD PRRMVSPLRR YTRHIDSSPY SPAYLSPPPE SSWRRTMAWG
160 170 180 190 200
NFPAEKGQLF RLPSALNRTS SDSALHTSVM NPSPQDTYPG PTPPSILPSR
210 220 230 240 250
RGGILDGEMD PKVPAIEENL LDDKHLLKPW DAKKLSSSSS RPRSCEVPGI
260 270 280 290 300
NIFPSPDQPA NVPVLPPAMN TGGSLPDLTN LHFPPPLPTP LDPEETAYPS
310 320 330 340 350
LSGGNSTSNL THTMTHLGIS RGMGLGPGYD APGLHSPLSH PSLQSSLSNP
360 370 380 390 400
NLQASLSSPQ PQLQGSHSHP SLPASSLARH VLPTTSLGHP SLSAPALSSS
410 420 430 440 450
SSSSSTSSPV LGAPSYPAST PGASPHHRRV PLSPLSLLAG PADARRSQQQ
460 470 480 490 500
LPKQFSPTMS PTLSSITQGV PLDTSKLSTD QRLPPYPYSS PSLVLPTQPH
510 520 530 540 550
TPKSLQQPGL PSQSCSVQSS GGQPPGRQSH YGTPYPPGPS GHGQQSYHRP
560 570 580 590 600
MSDFNLGNLE QFSMESPSAS LVLDPPGFSE GPGFLGGEGP MGGPQDPHTF
610 620 630 640 650
NHQNLTHCSR HGSGPNIILT GDSSPGFSKE IAAALAGVPG FEVSAAGLEL
660 670 680 690
GLGLEDELRM EPLGLEGLNM LSDPCALLPD PAVEESFRSD RLQ
Length:693
Mass (Da):73,302
Last modified:February 5, 2008 - v2
Checksum:iEE6C52E0ECDC1DF1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti323 – 325MGL → HGP in AAQ98857 (PubMed:14506290).Curated3
Sequence conflicti499P → S in BAD97279 (Ref. 2) Curated1

Polymorphismi

Variant Cys-379, under a dominant model, linked to a recessive mutation in LKB1, may be associated with susceptibility to type II or non-insulin-dependent diabetes mellitus (NIDDM).

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_038756147M → V.Corresponds to variant rs11264680dbSNPEnsembl.1
Natural variantiVAR_038757379R → C.2 PublicationsCorresponds to variant rs150423770dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY360172 mRNA. Translation: AAQ98857.1.
AK223559 mRNA. Translation: BAD97279.1.
AL358472 Genomic DNA. Translation: CAI14017.1.
BC028886 mRNA. Translation: AAH28886.1.
BC053562 mRNA. Translation: AAH53562.1.
CCDSiCCDS30875.1.
RefSeqiNP_859066.1. NM_181715.2.
UniGeneiHs.406392.

Genome annotation databases

EnsembliENST00000368633; ENSP00000357622; ENSG00000160741.
GeneIDi200186.
KEGGihsa:200186.
UCSCiuc057leo.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY360172 mRNA. Translation: AAQ98857.1.
AK223559 mRNA. Translation: BAD97279.1.
AL358472 Genomic DNA. Translation: CAI14017.1.
BC028886 mRNA. Translation: AAH28886.1.
BC053562 mRNA. Translation: AAH53562.1.
CCDSiCCDS30875.1.
RefSeqiNP_859066.1. NM_181715.2.
UniGeneiHs.406392.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HTMX-ray2.00A18-50[»]
ProteinModelPortaliQ53ET0.
SMRiQ53ET0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128308. 24 interactors.
DIPiDIP-29950N.
IntActiQ53ET0. 14 interactors.
MINTiMINT-1631979.
STRINGi9606.ENSP00000357622.

PTM databases

iPTMnetiQ53ET0.
PhosphoSitePlusiQ53ET0.

Polymorphism and mutation databases

BioMutaiCRTC2.
DMDMi167009135.

Proteomic databases

EPDiQ53ET0.
MaxQBiQ53ET0.
PaxDbiQ53ET0.
PeptideAtlasiQ53ET0.
PRIDEiQ53ET0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368633; ENSP00000357622; ENSG00000160741.
GeneIDi200186.
KEGGihsa:200186.
UCSCiuc057leo.1. human.

Organism-specific databases

CTDi200186.
DisGeNETi200186.
GeneCardsiCRTC2.
HGNCiHGNC:27301. CRTC2.
HPAiHPA028454.
HPA028465.
MIMi608972. gene.
neXtProtiNX_Q53ET0.
OpenTargetsiENSG00000160741.
PharmGKBiPA142672073.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGNT. Eukaryota.
ENOG410XPDQ. LUCA.
GeneTreeiENSGT00390000010652.
HOGENOMiHOG000111980.
HOVERGENiHBG058314.
InParanoidiQ53ET0.
KOiK16333.
OMAiHTLNHQN.
OrthoDBiEOG091G03YN.
PhylomeDBiQ53ET0.
TreeFamiTF321571.

Enzyme and pathway databases

ReactomeiR-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-400253. Circadian Clock.
SIGNORiQ53ET0.

Miscellaneous databases

ChiTaRSiCRTC2. human.
GeneWikiiCRTC2.
GenomeRNAii200186.
PROiQ53ET0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160741.
CleanExiHS_CRTC2.
ExpressionAtlasiQ53ET0. baseline and differential.
GenevisibleiQ53ET0. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiCRTC2_HUMAN
AccessioniPrimary (citable) accession number: Q53ET0
Secondary accession number(s): Q6UUV8, Q7Z3X7, Q8N332
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: November 30, 2016
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.