Regulation of lipid metabolism by PPARalpha (Homo sapiens)

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10, 27, 31, 43132013, 35161316301613, 1629, 374, 13, 14, 16, 1916, 25132416, 506, 16161316, 21, 3449413810, 11, 22, 27, 31...17, 18162, 913161613, 1616, 215, 10, 15, 22, 27...131613, 1610, 22, 27, 31, 43...161616231613, 16716lipid dropletnucleoplasmmitochondrial outer membranecytosolendoplasmic reticulum membraneperoxisomal matrixmitochondrial matrixFABP1PPARA NCOA6 MED15 PPARAMED12 CHD9 CPT2MED13L SREBF2(1-484) MED7 SIN3A LCHA RORA:EP300:CPT1AgeneNCOA2 NR1H2 ABCB4 geneSREBF1-1(1-490) CYP4A11 geneMED24 HMGCS1 geneNFYB MED8 G0S2APOA5NR1H3 PPARA gene SLC27A1 geneRORA:EP300:NPAS2geneMED30 NCOR1 ALAS1 geneAHR:TCDD:ARNTDCA SMARCD3 ALA CARM1 AA MED1 ALAS1RORA GLIPR1APOA2(24-100)MED26 ANGPTL4Palm GRHL1CARM1 GLIPR1 geneMED16 ABCB4HMGCR gene ACSL1 geneHDAC3 ACOX1 geneNCOA1 RGZ p-S-ARNTL ARNT HELZ2 TRIB3 geneNFYA CREBBP RXRA GPS2 ACSL1FDFT1MED29 FADS1TRIB3SULT2A1 geneSLC27A1TXNRD14xPalmC-CD36ALA PPARGC1A APOA1 geneCPT1ANCOA1 MED19 MED22 TBL1XR1 SIN3B-1 RXRB AGT geneHELZ2 LINA TNFRSF21 geneMED4 MED11 RGL1LINA HDAC3 HELZ2 Actos HMGCS1EPA CPT1A geneTGS1 HMGCR geneESRRAp-BMAL1:p-CLOCK,NPAS2:PPARA geneSIN3B-1 PPARGC1B G0S2 geneABCA1 genePLIN2NCOR2 NPAS2 gene MED17 ALAS1gene:NRF1:PPARGC1BMED21 CYP7A1MED1 UGT1A9AHRR p-S-NPAS2 MED9 SREBF1-3 PPARG:FattyAcid:RXRA:Mediator:Coactivator ComplexRXRA AHRR:ARNTCHD9 TBL1XR1 PPARA:RXRACoactivator complexME1NCOA1,2:RXRA:NR1H4:DCA,CDCA,LCHAFADS1 geneACOX1-1NPAS2 gene SREBP1A,1C,2:NF-Y:SP1:FDFT1 geneGRHL1 geneCPT2 geneRORA Corepressors ofPPARalphaHMGCS1 gene RXRA HDAC3 PEX11AAHR ARNT FAM120B ABCA1gene:NR1H2,3:RXR:NCOR:GPS2:TBL1:HDAC3TBL1XR1SREBF1-1(1-490) RXRA PeroxisomeProliferatorReceptor Element(PPRE)ACADMTBL1X ABCA1 gene HMGCR-1SREBP1A,2:NF-Y:HMGCRgeneFABP1 NCOR1 SREBF2(1-484) PPARA EPA PPARA:RXRACorepressor complexUGT1A9 gene9S-HODE MTF1 Zn2+ TXNRD1 geneCDK19 NR1H4 RXRA NCOA1 TGS1 ferriheme b NR1D1:heme:Corepressors:NPAS2 geneRGL1 geneSREBF1-3 MED13 p-S-CLOCK TBL1XR1 ANGPTL geneFABP1:ligands ofPPARAFABP1 geneNPAS2 geneTHRAP3 13(S')-HODE NRF1 CDK8 NFYA NFYB NFYB CCNC EP300 TBL1XNCOA2 MED31 TNFRSF21Palm NCOA6 NPAS2PLIN2 geneMED20 SREBF2(1-484) FHL2CD36 geneNCOA2 TIAM2 genePEX11A geneHMGCS2PPARG TBL1X NFYC RXRA SREBP1A,1C,2:NF-Y:HMGCS1 geneMED1 CYP4A11NFYC PPARA geneAPOA2 geneCPT1A gene MED23 ANKRD1 geneHMGCR gene CYP1A1 geneCREBBP Aryl hydrocarbonreceptor signallingSP1 NCOR2 CDCA ABCA1MED6 TIAM2Coactivators ofPPARalphaTCDD ALAS1 gene MED28 SIN3A NCOA3 PPARA:RXRAheterodimerEP300 Peroxisome Proliferator Receptor Element (PPRE) PPARA CYP7A1 geneANKRD1ACADM geneNCOA1 MED10 FHL2 geneHDAC3 HMGCS2 geneAPOA1(25-266)AA MED18 AGTNCOR1 NCOR1 MTF1dimer:12Zn2+:HMGCRgeneMED14 CYP1A1EP300 FDFT1 gene ARNT2 SMARCD3 FDFT1 geneMED25 Peroxisome Proliferator Receptor Element (PPRE) ME1 geneARNT2 TBL1X NFYA SULT2A1SREBF1-1(1-490) NFYC APOA5 geneNR1D1 NCOR2 CREBBP RXRAMED27 NCOA2 Peroxisome Proliferator Receptor Element (PPRE) 391, 3, 12465146464215, 4415, 444, 14, 194645828, 4726, 40484545


Description

Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma lipid levels.
PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds.
The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes.
Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 400206
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: May, Bruce

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History

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CompareRevisionActionTimeUserComment
115040view16:58, 25 January 2021ReactomeTeamReactome version 75
113484view11:56, 2 November 2020ReactomeTeamReactome version 74
112683view16:07, 9 October 2020ReactomeTeamReactome version 73
109289view21:21, 5 March 2020KhanspersReverted to version '11:47, 1 November 2018' by Khanspers
109272view15:00, 3 March 2020ClorisModified title
101600view11:47, 1 November 2018ReactomeTeamreactome version 66
101136view21:32, 31 October 2018ReactomeTeamreactome version 65
100664view20:05, 31 October 2018ReactomeTeamreactome version 64
100214view16:50, 31 October 2018ReactomeTeamreactome version 63
99765view15:16, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99324view12:47, 31 October 2018ReactomeTeamreactome version 62
93918view13:44, 16 August 2017ReactomeTeamreactome version 61
93495view11:25, 9 August 2017ReactomeTeamreactome version 61
88142view12:57, 26 July 2016RyanmillerOntology Term : 'fatty acid metabolic pathway' added !
88141view12:56, 26 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86591view09:21, 11 July 2016ReactomeTeamreactome version 56
83414view11:10, 18 November 2015ReactomeTeamVersion54
81776view10:35, 26 August 2015ReactomeTeamVersion53
77088view08:38, 17 July 2014ReactomeTeamFixed remaining interactions
76794view12:17, 16 July 2014ReactomeTeamFixed remaining interactions
76117view10:18, 11 June 2014ReactomeTeamRe-fixing comment source
75829view11:39, 10 June 2014ReactomeTeamReactome 48 Update
75190view09:39, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74834view10:06, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
13(S')-HODE MetaboliteCHEBI:34154 (ChEBI)
4xPalmC-CD36ProteinP16671 (Uniprot-TrEMBL)
9S-HODE MetaboliteCHEBI:34496 (ChEBI)
AA MetaboliteCHEBI:15843 (ChEBI)
ABCA1 gene ProteinENSG00000165029 (Ensembl)
ABCA1 geneGeneProductENSG00000165029 (Ensembl)
ABCA1ProteinO95477 (Uniprot-TrEMBL)
ABCA1gene:NR1H2,3:RXR:NCOR:GPS2:TBL1:HDAC3ComplexR-HSA-9024349 (Reactome)
ABCB4 geneGeneProductENSG00000005471 (Ensembl)
ABCB4ProteinP21439 (Uniprot-TrEMBL)
ACADM geneGeneProductENSG00000117054 (Ensembl)
ACADMProteinP11310 (Uniprot-TrEMBL)
ACOX1 geneGeneProductENSG00000161533 (Ensembl)
ACOX1-1ProteinQ15067-1 (Uniprot-TrEMBL)
ACSL1 geneGeneProductENSG00000151726 (Ensembl)
ACSL1ProteinP33121 (Uniprot-TrEMBL)
AGT geneGeneProductENSG00000135744 (Ensembl)
AGTProteinP01019 (Uniprot-TrEMBL)
AHR ProteinP35869 (Uniprot-TrEMBL)
AHR:TCDD:ARNTComplexR-HSA-8937203 (Reactome)
AHRR ProteinA9YTQ3 (Uniprot-TrEMBL)
AHRR:ARNTComplexR-HSA-8936835 (Reactome)
ALA MetaboliteCHEBI:27432 (ChEBI)
ALAS1 gene:NRF1:PPARGC1BComplexR-HSA-2466384 (Reactome)
ALAS1 gene ProteinENSG00000023330 (Ensembl)
ALAS1 geneGeneProductENSG00000023330 (Ensembl)
ALAS1ProteinP13196 (Uniprot-TrEMBL)
ANGPTL geneGeneProductENSG00000167772 (Ensembl)
ANGPTL4ProteinQ9BY76 (Uniprot-TrEMBL)
ANKRD1 geneGeneProductENSG00000148677 (Ensembl)
ANKRD1ProteinQ15327 (Uniprot-TrEMBL)
APOA1 geneGeneProductENSG00000118137 (Ensembl)
APOA1(25-266)ProteinP02647 (Uniprot-TrEMBL)
APOA2 geneGeneProductENSG00000158874 (Ensembl)
APOA2(24-100)ProteinP02652 (Uniprot-TrEMBL)
APOA5 geneGeneProductENSG00000110243 (Ensembl)
APOA5ProteinQ6Q788 (Uniprot-TrEMBL)
ARNT ProteinP27540 (Uniprot-TrEMBL)
ARNT2 ProteinQ9HBZ2 (Uniprot-TrEMBL)
Actos MetaboliteCHEBI:8228 (ChEBI)
Aryl hydrocarbon receptor signallingPathwayR-HSA-8937144 (Reactome) The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that belongs to the basic helix-loop-helix/PER-ARNT-SIM family of DNA binding proteins and controls the expression of a diverse set of genes. Two major types of environmental compounds can activate AHR signaling: halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAH) such as benzo(a)pyrene. Unliganded AHR forms a complex in the cytosol with two copies of 90kD heat shock protein (HSP90AB1), one X-associated protein (AIP), and one p23 molecular chaperone protein (PTGES3). After ligand binding and activation, the AHR complex translocates to the nucleus, disassociates from the chaperone subunits, dimerises with the aryl hydrocarbon receptor nuclear translocator (ARNT) and transactivates target genes via binding to xenobiotic response elements (XREs) in their promoter regions. AHR targets genes of Phase I and Phase II metabolism, such as cytochrome P450 1A1 (CYP1A1), cytochorme P450 1B1 (CYP1B1), NAD(P)H:quinone oxidoreductase I (NQO1) and aldehyde dehydrogenase 3 (ALHD3A1). This is thought to be an organism's response to foreign chemical exposure and normally, foreign chemicals are made less reactive by the induction and therefore increased activity of these enzymes (Beischlag et al. 2008).

AHR itself is regulated by the aryl hydrocarbon receptor repressor (AHRR, aka BHLHE77, KIAA1234), an evolutionarily conserved bHLH-PAS protein that inhibits both xenobiotic-induced and constitutively active AHR transcriptional activity in many species. AHRR resides predominantly in the nuclear compartment where it competes with AHR for binding to ARNT. As a result, there is competition between AHR:ARNT and AHRR:ARNT complexes for binding to XREs in target genes and AHRR can repress the transcription activity of AHR (Hahn et al. 2009, Haarmann-Stemmann & Abel 2006).
CARM1 ProteinQ86X55 (Uniprot-TrEMBL)
CCNC ProteinP24863 (Uniprot-TrEMBL)
CD36 geneGeneProductENSG00000135218 (Ensembl)
CDCA MetaboliteCHEBI:16755 (ChEBI)
CDK19 ProteinQ9BWU1 (Uniprot-TrEMBL)
CDK8 ProteinP49336 (Uniprot-TrEMBL)
CHD9 ProteinQ3L8U1 (Uniprot-TrEMBL)
CPT1A gene ProteinENSG00000110090 (Ensembl)
CPT1A geneGeneProductENSG00000110090 (Ensembl)
CPT1AProteinP50416 (Uniprot-TrEMBL)
CPT2 geneGeneProductENSG00000157184 (Ensembl)
CPT2ProteinP23786 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CYP1A1 geneGeneProductENSG00000140465 (Ensembl)
CYP1A1ProteinP04798 (Uniprot-TrEMBL)
CYP4A11 geneGeneProductENSG00000187048 (Ensembl)
CYP4A11ProteinQ02928 (Uniprot-TrEMBL)
CYP7A1 geneGeneProductENSG00000167910 (Ensembl)
CYP7A1ProteinP22680 (Uniprot-TrEMBL)
Coactivators of PPARalphaComplexR-HSA-400216 (Reactome)
Corepressors of PPARalphaComplexR-HSA-400207 (Reactome)
DCA MetaboliteCHEBI:28834 (ChEBI)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EPA MetaboliteCHEBI:28364 (ChEBI)
ESRRAProteinP11474 (Uniprot-TrEMBL)
FABP1 ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FABP1 geneGeneProductENSG00000163586 (Ensembl)
FABP1:ligands of PPARAComplexR-HSA-2026984 (Reactome)
FABP1ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FADS1 geneGeneProductENSG00000149485 (Ensembl)
FADS1ProteinO60427 (Uniprot-TrEMBL)
FAM120B ProteinQ96EK7 (Uniprot-TrEMBL)
FDFT1 gene ProteinENSG00000079459 (Ensembl)
FDFT1 geneGeneProductENSG00000079459 (Ensembl)
FDFT1ProteinP37268 (Uniprot-TrEMBL)
FHL2 geneGeneProductENSG00000115641 (Ensembl)
FHL2ProteinQ14192 (Uniprot-TrEMBL)
G0S2 geneGeneProductENSG00000123689 (Ensembl)
G0S2ProteinP27469 (Uniprot-TrEMBL)
GLIPR1 geneGeneProductENSG00000139278 (Ensembl)
GLIPR1ProteinP48060 (Uniprot-TrEMBL)
GPS2 ProteinQ13227 (Uniprot-TrEMBL)
GRHL1 geneGeneProductENSG00000134317 (Ensembl)
GRHL1ProteinQ9NZI5 (Uniprot-TrEMBL)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HELZ2 ProteinQ9BYK8 (Uniprot-TrEMBL)
HMGCR gene ProteinENSG00000113161 (Ensembl)
HMGCR geneGeneProductENSG00000113161 (Ensembl)
HMGCR-1ProteinP04035-1 (Uniprot-TrEMBL)
HMGCS1 gene ProteinENSG00000112972 (Ensembl)
HMGCS1 geneGeneProductENSG00000112972 (Ensembl)
HMGCS1ProteinQ01581 (Uniprot-TrEMBL)
HMGCS2 geneGeneProductENSG00000134240 (Ensembl)
HMGCS2ProteinP54868 (Uniprot-TrEMBL)
LCHA MetaboliteCHEBI:16325 (ChEBI)
LINA MetaboliteCHEBI:17351 (ChEBI)
ME1 geneGeneProductENSG00000065833 (Ensembl)
ME1ProteinP48163 (Uniprot-TrEMBL)
MED1 ProteinQ15648 (Uniprot-TrEMBL) MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
MED10 ProteinQ9BTT4 (Uniprot-TrEMBL)
MED11 ProteinQ9P086 (Uniprot-TrEMBL)
MED12 ProteinQ93074 (Uniprot-TrEMBL)
MED13 ProteinQ9UHV7 (Uniprot-TrEMBL)
MED13L ProteinQ71F56 (Uniprot-TrEMBL)
MED14 ProteinO60244 (Uniprot-TrEMBL)
MED15 ProteinQ96RN5 (Uniprot-TrEMBL)
MED16 ProteinQ9Y2X0 (Uniprot-TrEMBL)
MED17 ProteinQ9NVC6 (Uniprot-TrEMBL)
MED18 ProteinQ9BUE0 (Uniprot-TrEMBL)
MED19 ProteinA0JLT2 (Uniprot-TrEMBL)
MED20 ProteinQ9H944 (Uniprot-TrEMBL)
MED21 ProteinQ13503 (Uniprot-TrEMBL)
MED22 ProteinQ15528 (Uniprot-TrEMBL)
MED23 ProteinQ9ULK4 (Uniprot-TrEMBL)
MED24 ProteinO75448 (Uniprot-TrEMBL)
MED25 ProteinQ71SY5 (Uniprot-TrEMBL)
MED26 ProteinO95402 (Uniprot-TrEMBL)
MED27 ProteinQ6P2C8 (Uniprot-TrEMBL)
MED28 ProteinQ9H204 (Uniprot-TrEMBL)
MED29 ProteinQ9NX70 (Uniprot-TrEMBL)
MED30 ProteinQ96HR3 (Uniprot-TrEMBL)
MED31 ProteinQ9Y3C7 (Uniprot-TrEMBL)
MED4 ProteinQ9NPJ6 (Uniprot-TrEMBL)
MED6 ProteinO75586 (Uniprot-TrEMBL)
MED7 ProteinO43513 (Uniprot-TrEMBL)
MED8 ProteinQ96G25 (Uniprot-TrEMBL)
MED9 ProteinQ9NWA0 (Uniprot-TrEMBL)
MTF1

dimer:12Zn2+:HMGCR

gene		ComplexR-HSA-5660440 (Reactome)
MTF1 ProteinQ14872 (Uniprot-TrEMBL)
NCOA1 ProteinQ15788 (Uniprot-TrEMBL)
NCOA1,2:RXRA:NR1H4:DCA,CDCA,LCHAComplexR-HSA-5340274 (Reactome)
NCOA2 ProteinQ15596 (Uniprot-TrEMBL)
NCOA3 ProteinQ9Y6Q9 (Uniprot-TrEMBL)
NCOA6 ProteinQ14686 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NCOR2 ProteinQ9Y618 (Uniprot-TrEMBL)
NFYA ProteinP23511 (Uniprot-TrEMBL)
NFYB ProteinP25208 (Uniprot-TrEMBL)
NFYC ProteinQ13952 (Uniprot-TrEMBL)
NPAS2 gene ProteinENSG00000170485 (Ensembl)
NPAS2 geneGeneProductENSG00000170485 (Ensembl)
NPAS2ProteinQ99743 (Uniprot-TrEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1:heme:Corepressors:NPAS2 geneComplexR-HSA-5663274 (Reactome)
NR1H2 ProteinP55055 (Uniprot-TrEMBL)
NR1H3 ProteinQ13133 (Uniprot-TrEMBL)
NR1H4 ProteinQ96RI1 (Uniprot-TrEMBL)
NRF1 ProteinQ16656 (Uniprot-TrEMBL)
PEX11A geneGeneProductENSG00000166821 (Ensembl)
PEX11AProteinO75192 (Uniprot-TrEMBL)
PLIN2 geneGeneProductENSG00000147872 (Ensembl)
PLIN2ProteinQ99541 (Uniprot-TrEMBL)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARA gene ProteinENSG00000186951 (Ensembl)
PPARA geneGeneProductENSG00000186951 (Ensembl)
PPARA:RXRA Coactivator complexComplexR-HSA-400154 (Reactome)
PPARA:RXRA Corepressor complexComplexR-HSA-400196 (Reactome)
PPARA:RXRA heterodimerComplexR-HSA-400138 (Reactome)
PPARAProteinQ07869 (Uniprot-TrEMBL)
PPARG ProteinP37231 (Uniprot-TrEMBL)
PPARG:Fatty Acid:RXRA:Mediator:Coactivator ComplexComplexR-HSA-381367 (Reactome)
PPARGC1A ProteinQ9UBK2 (Uniprot-TrEMBL)
PPARGC1B ProteinQ86YN6 (Uniprot-TrEMBL)
Palm MetaboliteCHEBI:15756 (ChEBI)
Peroxisome

Proliferator Receptor Element

(PPRE)		R-ALL-422139 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
Peroxisome Proliferator Receptor Element (PPRE) R-ALL-422139 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
RGL1 geneGeneProductENSG00000143344 (Ensembl)
RGL1ProteinQ9NZL6 (Uniprot-TrEMBL)
RGZ MetaboliteCHEBI:50122 (ChEBI)
RORA ProteinP35398 (Uniprot-TrEMBL)
RORA:EP300:CPT1A geneComplexR-HSA-5663244 (Reactome)
RORA:EP300:NPAS2 geneComplexR-HSA-5663257 (Reactome)
RXRA ProteinP19793 (Uniprot-TrEMBL)
RXRAProteinP19793 (Uniprot-TrEMBL)
RXRB ProteinP28702 (Uniprot-TrEMBL)
SIN3A ProteinQ96ST3 (Uniprot-TrEMBL)
SIN3B-1 ProteinO75182-1 (Uniprot-TrEMBL)
SLC27A1 geneGeneProductENSG00000130304 (Ensembl)
SLC27A1ProteinQ6PCB7 (Uniprot-TrEMBL)
SMARCD3 ProteinQ6STE5 (Uniprot-TrEMBL)
SP1 ProteinP08047 (Uniprot-TrEMBL)
SREBF1-1(1-490) ProteinP36956-1 (Uniprot-TrEMBL)
SREBF1-3 ProteinP36956-3 (Uniprot-TrEMBL)
SREBF2(1-484) ProteinQ12772 (Uniprot-TrEMBL)
SREBP1A,1C,2:NF-Y:HMGCS1 geneComplexR-HSA-2426129 (Reactome)
SREBP1A,1C,2:NF-Y:SP1:FDFT1 geneComplexR-HSA-2426135 (Reactome)
SREBP1A,2:NF-Y:HMGCR geneComplexR-HSA-2426128 (Reactome)
SULT2A1 geneGeneProductENSG00000105398 (Ensembl)
SULT2A1ProteinQ06520 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (Uniprot-TrEMBL)
TBL1XR1ProteinQ9BZK7 (Uniprot-TrEMBL)
TCDD MetaboliteCHEBI:28119 (ChEBI)
TGS1 ProteinQ96RS0 (Uniprot-TrEMBL)
THRAP3 ProteinQ9Y2W1 (Uniprot-TrEMBL)
TIAM2 geneGeneProductENSG00000146426 (Ensembl)
TIAM2ProteinQ8IVF5 (Uniprot-TrEMBL)
TNFRSF21 geneGeneProductENSG00000146072 (Ensembl)
TNFRSF21ProteinO75509 (Uniprot-TrEMBL)
TRIB3 geneGeneProductENSG00000101255 (Ensembl)
TRIB3ProteinQ96RU7 (Uniprot-TrEMBL)
TXNRD1 geneGeneProductENSG00000198431 (Ensembl)
TXNRD1ProteinQ16881 (Uniprot-TrEMBL)
UGT1A9 geneGeneProductENSG00000241119 (Ensembl)
UGT1A9ProteinO60656 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
p-BMAL1:p-CLOCK,NPAS2:PPARA geneComplexR-HSA-5663137 (Reactome)
p-S-ARNTL ProteinO00327 (Uniprot-TrEMBL)
p-S-CLOCK ProteinO15516 (Uniprot-TrEMBL)
p-S-NPAS2 ProteinQ99743 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
4xPalmC-CD36ArrowR-HSA-560517 (Reactome)
ABCA1 geneR-HSA-1989765 (Reactome)
ABCA1ArrowR-HSA-1989765 (Reactome)
ABCA1gene:NR1H2,3:RXR:NCOR:GPS2:TBL1:HDAC3TBarR-HSA-1989765 (Reactome)
ABCB4 geneR-HSA-1989762 (Reactome)
ABCB4ArrowR-HSA-1989762 (Reactome)
ACADM geneR-HSA-1989745 (Reactome)
ACADMArrowR-HSA-1989745 (Reactome)
ACOX1 geneR-HSA-1989749 (Reactome)
ACOX1-1ArrowR-HSA-1989749 (Reactome)
ACSL1 geneR-HSA-1989778 (Reactome)
ACSL1ArrowR-HSA-1989778 (Reactome)
AGT geneR-HSA-1989774 (Reactome)
AGTArrowR-HSA-1989774 (Reactome)
AHRR:ARNTTBarR-HSA-1989764 (Reactome)
ALAS1 geneR-HSA-1592238 (Reactome)
ALAS1ArrowR-HSA-1592238 (Reactome)
ANGPTL geneR-HSA-560473 (Reactome)
ANGPTL4ArrowR-HSA-560473 (Reactome)
ANKRD1 geneR-HSA-1989779 (Reactome)
ANKRD1ArrowR-HSA-1989779 (Reactome)
APOA1 geneR-HSA-1989754 (Reactome)
APOA1(25-266)ArrowR-HSA-1989754 (Reactome)
APOA2 geneR-HSA-1989776 (Reactome)
APOA2(24-100)ArrowR-HSA-1989776 (Reactome)
APOA5 geneR-HSA-1989761 (Reactome)
APOA5ArrowR-HSA-1989761 (Reactome)
ArrowR-HSA-1368065 (Reactome)
ArrowR-HSA-1592238 (Reactome)
ArrowR-HSA-1801587 (Reactome)
ArrowR-HSA-1989764 (Reactome)
ArrowR-HSA-879724 (Reactome)
CD36 geneR-HSA-560517 (Reactome)
CPT1A geneR-HSA-1801587 (Reactome)
CPT1AArrowR-HSA-1801587 (Reactome)
CPT2 geneR-HSA-1989773 (Reactome)
CPT2ArrowR-HSA-1989773 (Reactome)
CYP1A1 geneR-HSA-1989764 (Reactome)
CYP1A1ArrowR-HSA-1989764 (Reactome)
CYP4A11 geneR-HSA-1989755 (Reactome)
CYP4A11ArrowR-HSA-1989755 (Reactome)
CYP7A1 geneR-HSA-1989746 (Reactome)
CYP7A1ArrowR-HSA-1989746 (Reactome)
Coactivators of PPARalphaR-HSA-400143 (Reactome)
Corepressors of PPARalphaArrowR-HSA-400143 (Reactome)
Corepressors of PPARalphaR-HSA-400183 (Reactome)
FABP1 geneR-HSA-1989751 (Reactome)
FABP1:ligands of PPARAR-HSA-400143 (Reactome)
FABP1ArrowR-HSA-1989751 (Reactome)
FABP1ArrowR-HSA-400143 (Reactome)
FADS1 geneR-HSA-1989757 (Reactome)
FADS1ArrowR-HSA-1989757 (Reactome)
FDFT1 geneR-HSA-1655850 (Reactome)
FDFT1ArrowR-HSA-1655850 (Reactome)
FHL2 geneR-HSA-1989747 (Reactome)
FHL2ArrowR-HSA-1989747 (Reactome)
G0S2 geneR-HSA-1989759 (Reactome)
G0S2ArrowR-HSA-1989759 (Reactome)
GLIPR1 geneR-HSA-1989772 (Reactome)
GLIPR1ArrowR-HSA-1989772 (Reactome)
GRHL1 geneR-HSA-1989748 (Reactome)
GRHL1ArrowR-HSA-1989748 (Reactome)
HMGCR geneR-HSA-1655826 (Reactome)
HMGCR-1ArrowR-HSA-1655826 (Reactome)
HMGCS1 geneR-HSA-1655848 (Reactome)
HMGCS1ArrowR-HSA-1655848 (Reactome)
HMGCS2 geneR-HSA-1989760 (Reactome)
HMGCS2ArrowR-HSA-1989760 (Reactome)
ME1 geneR-HSA-1989756 (Reactome)
ME1ArrowR-HSA-1989756 (Reactome)
MTF1

dimer:12Zn2+:HMGCR

gene		TBarR-HSA-1655826 (Reactome)
NCOA1,2:RXRA:NR1H4:DCA,CDCA,LCHATBarR-HSA-1989746 (Reactome)
NPAS2 geneR-HSA-1368065 (Reactome)
NPAS2ArrowR-HSA-1368065 (Reactome)
NR1D1:heme:Corepressors:NPAS2 geneTBarR-HSA-1368065 (Reactome)
PEX11A geneR-HSA-1989753 (Reactome)
PEX11AArrowR-HSA-1989753 (Reactome)
PLIN2 geneR-HSA-1989770 (Reactome)
PLIN2ArrowR-HSA-1989770 (Reactome)
PPARA geneR-HSA-879724 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1368065 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1592238 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1655826 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1655848 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1655850 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1801587 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989745 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989746 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989747 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989748 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989749 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989750 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989751 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989752 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989753 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989754 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989755 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989756 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989757 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989758 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989759 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989760 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989761 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989762 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989764 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989765 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989767 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989768 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989770 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989771 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989772 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989773 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989774 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989775 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989776 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989777 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989778 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989779 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-400143 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-560473 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-560517 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-879724 (Reactome)
PPARA:RXRA Corepressor complexArrowR-HSA-400183 (Reactome)
PPARA:RXRA Corepressor complexR-HSA-400143 (Reactome)
PPARA:RXRA heterodimerArrowR-HSA-400204 (Reactome)
PPARA:RXRA heterodimerR-HSA-400183 (Reactome)
PPARAArrowR-HSA-879724 (Reactome)
PPARAR-HSA-400204 (Reactome)
PPARG:Fatty Acid:RXRA:Mediator:Coactivator ComplexArrowR-HSA-560473 (Reactome)
PPARG:Fatty Acid:RXRA:Mediator:Coactivator ComplexArrowR-HSA-560517 (Reactome)
Peroxisome

Proliferator Receptor Element

(PPRE)		R-HSA-400204 (Reactome)
R-HSA-1368065 (Reactome) The NPAS2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Transcription of NPAS2 is enhanced by the RORA:Coactivator complex and repressed by the REV-ERBA:Corepressor complex.
R-HSA-1592238 (Reactome) The ALAS1 gene is transcribed to yield mRNA and the mRNA is translated in the cytosol to yield precursor protein. The ALAS1 precursor is imported into the mitochodrial matrix where it catalyzes the synthesis of 5-aminolevulinate from glycine and succinyl-CoA as part of heme biosynthesis.
R-HSA-1655826 (Reactome) The HMGCR gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1655848 (Reactome) The HMGCS1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1655850 (Reactome) The FDFT1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1801587 (Reactome) The CPT1A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989745 (Reactome) The ACADM gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989746 (Reactome) The CYP7A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989747 (Reactome) The FHL2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989748 (Reactome) The GRHL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989749 (Reactome) The ACOX1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989750 (Reactome) The FATP1 (SLC27A1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989751 (Reactome) The FABP1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989752 (Reactome) The TXNRD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989753 (Reactome) The PEX11A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989754 (Reactome) The APOA1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989755 (Reactome) The CYP4A11 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989756 (Reactome) The ME1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989757 (Reactome) The FADS1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989758 (Reactome) The UGT1A9 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989759 (Reactome) The G0S2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989760 (Reactome) The HMGCS2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989761 (Reactome) The APOA5 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989762 (Reactome) The ABCB4 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989764 (Reactome) The CYP1A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein (van der Meer et al. 2010, Rakhshandehroo et al. 2009). The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that controls the expression of a diverse set of genes. AHR acts as a sensor of polyaromatic chemicals, which upon activation, translocates to the nucleus and binds with the aryl hydrocarbon receptor nuclear translocator (ARNT) to transactivate target genes via binding to xenobiotic response elements (XREs) in their promoter regions. AHR targets genes of Phase I and Phase II metabolism, such as cytochrome P450 1A1 (CYP1A1) (Beischlag et al. 2008). AHR is regulated by the aryl hydrocarbon receptor repressor (AHRR, aka BHLHE77, KIAA1234) that inhibits both xenobiotic-induced and constitutively active AHR transcriptional activity in many species (Hahn et al. 2009, Haarmann-Stemmann & Abel 2006).

R-HSA-1989765 (Reactome) The ATP-binding cassette transporter A1 (ABCA1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989767 (Reactome) The TRIB3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989768 (Reactome) The TIAM2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989770 (Reactome) The Adipophilin (PLIN2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989771 (Reactome) The TNFRSF21 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989772 (Reactome) The GLIPR1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989773 (Reactome) The CPT2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989774 (Reactome) The AGT gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989775 (Reactome) The SULT2A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989776 (Reactome) The APOA2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989777 (Reactome) The RGL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989778 (Reactome) The ACSL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1989779 (Reactome) The ANKRD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-400143 (Reactome) PPAR-alpha is activated by binding polyunsaturated fatty acids especially those having 18-22 carbon groups and 2-6 double bonds. These ligands bind the C-terminal region of PPAR-alpha and include linoleic acid, linolenic acids, arachidonic acid, and eicosapentaenoic acid. The fibrate drugs are also agonists of PPAR-alpha.
Binding of a ligand causes a conformational change in PPAR-alpha so that it recruits coactivators. By analogy with the closely related receptor PPAR-gamma, PPAR-alpha probably binds TBL1 and TBLR1, which are responsible for recruiting the 19S proteasome to degrade corepressors during the exchange of corepressors for coactivators. The coactivators belong to the CBP-SRC-HAT complex (CBP/p300, SRC1, SRC2, SRC3, CARM1, SWI/SNF, BAF60C, PRIC320, and PRIC285), the ASC complex (PRIP/ASC2, PIMT), and the TRAP-DRIP-ARC-MEDIATOR complex (TRAP130, PBP/TRAP220). The coactivators contain LXXLL motifs (Nuclear Receptor Boxes) that interact with the AF-2 region in nuclear receptors such as PPAR-alpha.
R-HSA-400183 (Reactome) In the absence of activating ligands of PPAR-alpha, the PPAR-alpha:RXR-alpha heterodimers recruit corepressors NCoR1, NCoR2(SMRT), and histone deacetylases (HDACs) to genes regulated by PPAR-alpha. The corepressors maintain chromatin at the gene in an inactive conformation and prevent expression of the gene.
R-HSA-400204 (Reactome) Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a type II nuclear receptor (its subcellular location is independent of ligand binding) related to PPAR-beta/delta and PPAR-gamma. PPAR-alpha is expressed highly in the liver where if functions to control lipid metabolism, especially fatty acid oxidation.
PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha). The heterodimers bind peroxisome proliferator receptor elements (PPREs) in and around genes regulated by PPAR-alpha.
R-HSA-560473 (Reactome) The ANGPTL4 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-560517 (Reactome) The Platelet glycoprotein IV gene (CD36, PAS IV, GPIV) is transcribed to yield mRNA and the mRNA is translated to yield proteind.
R-HSA-879724 (Reactome) The PPARA gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) heterodimers bind the scond intron of the PPARA gene and activate transcription of PPARA.
RGL1 geneR-HSA-1989777 (Reactome)
RGL1ArrowR-HSA-1989777 (Reactome)
RXRAR-HSA-400204 (Reactome)
SLC27A1 geneR-HSA-1989750 (Reactome)
SLC27A1ArrowR-HSA-1989750 (Reactome)
SREBP1A,1C,2:NF-Y:HMGCS1 geneArrowR-HSA-1655848 (Reactome)
SREBP1A,1C,2:NF-Y:SP1:FDFT1 geneArrowR-HSA-1655850 (Reactome)
SREBP1A,2:NF-Y:HMGCR geneArrowR-HSA-1655826 (Reactome)
SULT2A1 geneR-HSA-1989775 (Reactome)
SULT2A1ArrowR-HSA-1989775 (Reactome)
TBL1XR-HSA-400183 (Reactome)
TBL1XR1R-HSA-400183 (Reactome)
TIAM2 geneR-HSA-1989768 (Reactome)
TIAM2ArrowR-HSA-1989768 (Reactome)
TNFRSF21 geneR-HSA-1989771 (Reactome)
TNFRSF21ArrowR-HSA-1989771 (Reactome)
TRIB3 geneR-HSA-1989767 (Reactome)
TRIB3ArrowR-HSA-1989767 (Reactome)
TXNRD1 geneR-HSA-1989752 (Reactome)
TXNRD1ArrowR-HSA-1989752 (Reactome)
UGT1A9 geneR-HSA-1989758 (Reactome)
UGT1A9ArrowR-HSA-1989758 (Reactome)
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