Regulation of lipid metabolism by PPARalpha (Homo sapiens)

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23, 27, 33, 481111116, 11491173266, 8, 4411, 2111, 38115, 11, 214, 23, 27, 33, 41...11, 151166141, 4, 13, 23, 27...62011, 16111961111261164, 10, 23, 27, 33...116, 116, 116, 112113918, 46116, 931, 426, 11lipid particleCoactivators ofPPARalpha[nucleoplasm]mitochondrial outer membraneLigands of PPARA[nucleoplasm]nucleoplasmActivated PPARG:RXRA[nucleoplasm]PPARA:RXRAHeterodimer[nucleoplasm]endoplasmic reticulum membraneFABP1:Ligands ofPPARA [nucleoplasm]PPARG:Fatty AcidLigand [nucleoplasm]SREBP1A/1C/2:NF-Y:HMGCS1gene [nucleoplasm]SREBP1A/2:NF-Y:HMGCRgene [nucleoplasm]Activated PPARA:RXRAHeterodimer[nucleoplasm]NR1D1(REV-ERBA):heme:Corepressor[nucleoplasm]mitochondrial matrixNF-Y [nucleoplasm]TEAD:YAP1[nucleoplasm]SREBP1A/1C/2 Dimer[nucleoplasm]ROR-alpha:Coactivator[nucleoplasm]SREBF1A,1C,2 cleavedby S2P [nucleoplasm]TEAD [nucleoplasm]Mediator Complex(consensus)[nucleoplasm]ALAS1gene:NRF1:PPARGC1B[nucleoplasm]SREBF1A,1C,2 cleavedby S2P [nucleoplasm]cytosolPPARA:RXRAHeterodimer[nucleoplasm]SREBP1A/2 Dimer[nucleoplasm]NF-Y [nucleoplasm]TEAD:WWTR1(TAZ)[nucleoplasm]PPARA:RXRA RepressorComplex[nucleoplasm]Ligands of PPARA[nucleoplasm]p-BMAL1:p-CLOCK/NPAS2:DNA[nucleoplasm]TEAD [nucleoplasm]SREBP1A/1C/2 Dimer[nucleoplasm]p-CLOCK/p-NPAS2[nucleoplasm]PPARA: Fatty AcidComplex (ActivatedPPARA) [nucleoplasm]peroxisomal matrixNF-Y [nucleoplasm]Ligands of PPARG[nucleoplasm]SREBP1A/1C/2:NF-Y:SP1:FDFT1gene [nucleoplasm]SREBF1A,2[nucleoplasm]Corepressors ofPPARalpha[nucleoplasm]PPARA:RXRACoactivator Complex[nucleoplasm]PPARG:FattyAcid:RXRA:Mediator:CoactivatorComplex[nucleoplasm]NR1D1(REV-ERBA):heme[nucleoplasm]p-S-ARNTL[nucleoplasm]ROR-alpha:CoactivatorCDK8 [nucleoplasm]HMGCR-1MED20 [nucleoplasm]SIN3B-1[nucleoplasm]NCOA1 [nucleoplasm]TEAD1 [nucleoplasm]PEX11ARORA [nucleoplasm]SREBF2(1-484)[nucleoplasm]HMGCR gene[nucleoplasm]ALA [nucleoplasm]HMGCS1 gene[nucleoplasm]CPT2TEAD4 [nucleoplasm]CYP1A1YAP1 [nucleoplasm]CYP4A11SREBF2(1-484)[nucleoplasm]Palm [nucleoplasm]CYP7A1RGZ [nucleoplasm]CARM1(2-608)[nucleoplasm]MED27 [nucleoplasm]TEAD1 [nucleoplasm]EP300(1-2414)[nucleoplasm]MED11 [nucleoplasm]APOA2(24-100)FDFT1 gene[nucleoplasm]MED9 [nucleoplasm]LINA [nucleoplasm]Palm [nucleoplasm]PPARATBL1X [nucleoplasm]MED13 [nucleoplasm]NR1D1 [nucleoplasm]TXNRD1Actos [nucleoplasm]ACADMGLIPR1NR1D1(REV-ERBA):heme:CorepressorABCB4APOA5PPARA [nucleoplasm]FADS1(1-444)LINA [nucleoplasm]TEAD2 [nucleoplasm]SREBF1-1(1-490)[nucleoplasm]MED24 [nucleoplasm]EPA [nucleoplasm]ANGPTL4PPARG:FattyAcid:RXRA:Mediator:CoactivatorComplexferriheme b[nucleoplasm]FABP1:Ligands ofPPARAPPARA:RXRA RepressorComplexNCOR2 [nucleoplasm]TEAD:YAP1TBL1X [nucleoplasm]EPA [nucleoplasm]ABCA1MED22 [nucleoplasm]CHD9 [nucleoplasm]HELZ2 [nucleoplasm]NFYB [nucleoplasm]HELZ2 [nucleoplasm]MED30(1-178)[nucleoplasm]FDFT1MED31 [nucleoplasm]TEAD3(1-435)[nucleoplasm]13(S')-HODE[nucleoplasm]SREBF1-3[nucleoplasm]SREBP1A/1C/2:NF-Y:HMGCS1geneAGTNCOA2 [nucleoplasm]WWTR1 [nucleoplasm]MED25 [nucleoplasm]CCNC [nucleoplasm]4xPalmC-CD36SIN3A [nucleoplasm]MED12 [nucleoplasm]SULT2A1(2-285)NFYB [nucleoplasm]9S-HODE[nucleoplasm]SREBF1-1(1-490)[nucleoplasm]MED10(2-135)[nucleoplasm]RXRA [nucleoplasm]MED1 [nucleoplasm]MED19 [nucleoplasm]ACOX1-1MED15 [nucleoplasm]G0S2SREBP1A/1C/2:NF-Y:SP1:FDFT1geneNCOR1 [nucleoplasm]MED23 [nucleoplasm]CREBBP(2-2442)[nucleoplasm]HMGCS2p-BMAL1:p-CLOCK/NPAS2:DNAPPARA [nucleoplasm]GRHL1Corepressors ofPPARalphaSMARCD3[nucleoplasm]TBL1XR1FHL2MED18 [nucleoplasm]MED4 [nucleoplasm]SREBP1A/2:NF-Y:HMGCRgeneCoactivators ofPPARalphaMED29(2-200)[nucleoplasm]ALAS1gene:NRF1:PPARGC1BMED17 [nucleoplasm]AA [nucleoplasm]ACSL1FABP1TBL1XR1[nucleoplasm]SREBF1-3[nucleoplasm]ALA [nucleoplasm]p-S-CLOCK[nucleoplasm]TEAD4 [nucleoplasm]SLC27A1NCOA1 [nucleoplasm]RGL1NFYC [nucleoplasm]TNFRSF21UGT1A9FABP1 [nucleoplasm]NPAS2TBL1XR1[nucleoplasm]p-S-NPAS2[nucleoplasm]CDK19 [nucleoplasm]CTGFPPARGC1A[nucleoplasm]HDAC3 [nucleoplasm]CREBBP(2-2442)[nucleoplasm]NRF1 [nucleoplasm]SREBF2(1-484)[nucleoplasm]MED16 [nucleoplasm]ALAS1 gene[nucleoplasm]NFYC [nucleoplasm]RXRAAA [nucleoplasm]NFYC [nucleoplasm]TBL1XSP1(1-785)[nucleoplasm]PPARA:RXRACoactivator ComplexPPARA [nucleoplasm]MED6 [nucleoplasm]RXRA [nucleoplasm]SREBF1-1(1-490)[nucleoplasm]NFYB [nucleoplasm]ANKRD1NCOA3 [nucleoplasm]MED7 [nucleoplasm]ALAS1PPARG [nucleoplasm]NCOR1 [nucleoplasm]PPARGC1A[nucleoplasm]MED8 [nucleoplasm]MED14 [nucleoplasm]NFYA [nucleoplasm]PeroxisomeProliferatorReceptor Element(PPRE)TGS1 [nucleoplasm]PPARGC1B[nucleoplasm]MED26 [nucleoplasm]HMGCS1TEAD:WWTR1(TAZ)NCOA6 [nucleoplasm]TEAD2 [nucleoplasm]ME1HDAC3 [nucleoplasm]EP300(1-2414)[nucleoplasm]TIAM2(2-1701)MED1 [nucleoplasm]CPT1APPARA:RXRAHeterodimerPLIN2MED13L [nucleoplasm]TEAD3(1-435)[nucleoplasm]APOA1(25-266)NFYA [nucleoplasm]TRIB3ESRRANCOA2 [nucleoplasm]NFYA [nucleoplasm]MED21 [nucleoplasm]RXRA [nucleoplasm]RXRA [nucleoplasm]243, 47812, 17, 3625, 35373, 478, 44302422, 281, 291, 292440


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.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=400206

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Bibliography

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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 [nucleoplasm]MetaboliteCHEBI:34154 (ChEBI)
4xPalmC-CD36ProteinP16671 (Uniprot-TrEMBL)
9S-HODE [nucleoplasm]MetaboliteCHEBI:34496 (ChEBI)
AA [nucleoplasm]MetaboliteCHEBI:15843 (ChEBI)
ABCA1ProteinO95477 (Uniprot-TrEMBL)
ABCB4ProteinP21439 (Uniprot-TrEMBL)
ACADMProteinP11310 (Uniprot-TrEMBL)
ACOX1-1ProteinQ15067-1 (Uniprot-TrEMBL)
ACSL1ProteinP33121 (Uniprot-TrEMBL)
AGTProteinP01019 (Uniprot-TrEMBL)
ALA [nucleoplasm]MetaboliteCHEBI:27432 (ChEBI)
ALAS1 gene:NRF1:PPARGC1BComplexREACT_151863 (Reactome)
ALAS1 gene [nucleoplasm]ProteinENSG00000023330 (ENSEMBL)
ALAS1ProteinP13196 (Uniprot-TrEMBL)
ANGPTL4ProteinQ9BY76 (Uniprot-TrEMBL)
ANKRD1ProteinQ15327 (Uniprot-TrEMBL)
APOA1(25-266)ProteinP02647 (Uniprot-TrEMBL)
APOA2(24-100)ProteinP02652 (Uniprot-TrEMBL)
APOA5ProteinQ6Q788 (Uniprot-TrEMBL)
Actos [nucleoplasm]MetaboliteCHEBI:8228 (ChEBI)
CARM1(2-608) [nucleoplasm]ProteinQ86X55 (Uniprot-TrEMBL)
CCNC [nucleoplasm]ProteinP24863 (Uniprot-TrEMBL)
CDK19 [nucleoplasm]ProteinQ9BWU1 (Uniprot-TrEMBL)
CDK8 [nucleoplasm]ProteinP49336 (Uniprot-TrEMBL)
CHD9 [nucleoplasm]ProteinQ3L8U1 (Uniprot-TrEMBL)
CPT1AProteinP50416 (Uniprot-TrEMBL)
CPT2ProteinP23786 (Uniprot-TrEMBL)
CREBBP(2-2442) [nucleoplasm]ProteinQ92793 (Uniprot-TrEMBL)
CTGFProteinP29279 (Uniprot-TrEMBL)
CYP1A1ProteinP04798 (Uniprot-TrEMBL)
CYP4A11ProteinQ02928 (Uniprot-TrEMBL)
CYP7A1ProteinP22680 (Uniprot-TrEMBL)
Coactivators of PPARalphaProteinREACT_20313 (Reactome)
Corepressors of PPARalphaProteinREACT_19786 (Reactome)
EP300(1-2414) [nucleoplasm]ProteinQ09472 (Uniprot-TrEMBL)
EPA [nucleoplasm]MetaboliteCHEBI:28364 (ChEBI)
ESRRAProteinP11474 (Uniprot-TrEMBL)
FABP1 [nucleoplasm]ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FABP1:Ligands of PPARAComplexREACT_119390 (Reactome)
FABP1ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FADS1(1-444)ProteinO60427 (Uniprot-TrEMBL)
FDFT1 gene [nucleoplasm]ProteinENSG00000079459 (ENSEMBL)
FDFT1ProteinP37268 (Uniprot-TrEMBL)
FHL2ProteinQ14192 (Uniprot-TrEMBL)
G0S2ProteinP27469 (Uniprot-TrEMBL)
GLIPR1ProteinP48060 (Uniprot-TrEMBL)
GRHL1ProteinQ9NZI5 (Uniprot-TrEMBL)
HDAC3 [nucleoplasm]ProteinO15379 (Uniprot-TrEMBL)
HELZ2 [nucleoplasm]ProteinQ9BYK8 (Uniprot-TrEMBL)
HMGCR gene [nucleoplasm]ProteinENSG00000113161 (ENSEMBL)
HMGCR-1ProteinP04035-1 (Uniprot-TrEMBL)
HMGCS1 gene [nucleoplasm]ProteinENSG00000112972 (ENSEMBL)
HMGCS1ProteinQ01581 (Uniprot-TrEMBL)
HMGCS2ProteinP54868 (Uniprot-TrEMBL)
LINA [nucleoplasm]MetaboliteCHEBI:17351 (ChEBI)
ME1ProteinP48163 (Uniprot-TrEMBL)
MED1 [nucleoplasm]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(2-135) [nucleoplasm]ProteinQ9BTT4 (Uniprot-TrEMBL)
MED11 [nucleoplasm]ProteinQ9P086 (Uniprot-TrEMBL)
MED12 [nucleoplasm]ProteinQ93074 (Uniprot-TrEMBL)
MED13 [nucleoplasm]ProteinQ9UHV7 (Uniprot-TrEMBL)
MED13L [nucleoplasm]ProteinQ71F56 (Uniprot-TrEMBL)
MED14 [nucleoplasm]ProteinO60244 (Uniprot-TrEMBL)
MED15 [nucleoplasm]ProteinQ96RN5 (Uniprot-TrEMBL)
MED16 [nucleoplasm]ProteinQ9Y2X0 (Uniprot-TrEMBL)
MED17 [nucleoplasm]ProteinQ9NVC6 (Uniprot-TrEMBL)
MED18 [nucleoplasm]ProteinQ9BUE0 (Uniprot-TrEMBL)
MED19 [nucleoplasm]ProteinA0JLT2 (Uniprot-TrEMBL)
MED20 [nucleoplasm]ProteinQ9H944 (Uniprot-TrEMBL)
MED21 [nucleoplasm]ProteinQ13503 (Uniprot-TrEMBL)
MED22 [nucleoplasm]ProteinQ15528 (Uniprot-TrEMBL)
MED23 [nucleoplasm]ProteinQ9ULK4 (Uniprot-TrEMBL)
MED24 [nucleoplasm]ProteinO75448 (Uniprot-TrEMBL)
MED25 [nucleoplasm]ProteinQ71SY5 (Uniprot-TrEMBL)
MED26 [nucleoplasm]ProteinO95402 (Uniprot-TrEMBL)
MED27 [nucleoplasm]ProteinQ6P2C8 (Uniprot-TrEMBL)
MED29(2-200) [nucleoplasm]ProteinQ9NX70 (Uniprot-TrEMBL)
MED30(1-178) [nucleoplasm]ProteinQ96HR3 (Uniprot-TrEMBL)
MED31 [nucleoplasm]ProteinQ9Y3C7 (Uniprot-TrEMBL)
MED4 [nucleoplasm]ProteinQ9NPJ6 (Uniprot-TrEMBL)
MED6 [nucleoplasm]ProteinO75586 (Uniprot-TrEMBL)
MED7 [nucleoplasm]ProteinO43513 (Uniprot-TrEMBL)
MED8 [nucleoplasm]ProteinQ96G25 (Uniprot-TrEMBL)
MED9 [nucleoplasm]ProteinQ9NWA0 (Uniprot-TrEMBL)
NCOA1 [nucleoplasm]ProteinQ15788 (Uniprot-TrEMBL)
NCOA2 [nucleoplasm]ProteinQ15596 (Uniprot-TrEMBL)
NCOA3 [nucleoplasm]ProteinQ9Y6Q9 (Uniprot-TrEMBL)
NCOA6 [nucleoplasm]ProteinQ14686 (Uniprot-TrEMBL)
NCOR1 [nucleoplasm]ProteinO75376 (Uniprot-TrEMBL)
NCOR2 [nucleoplasm]ProteinQ9Y618 (Uniprot-TrEMBL)
NFYA [nucleoplasm]ProteinP23511 (Uniprot-TrEMBL)
NFYB [nucleoplasm]ProteinP25208 (Uniprot-TrEMBL)
NFYC [nucleoplasm]ProteinQ13952 (Uniprot-TrEMBL)
NPAS2ProteinQ99743 (Uniprot-TrEMBL)
NR1D1 (REV-ERBA):heme:CorepressorComplexREACT_111441 (Reactome)
NR1D1 [nucleoplasm]ProteinP20393 (Uniprot-TrEMBL)
NRF1 [nucleoplasm]ProteinQ16656 (Uniprot-TrEMBL)
PEX11AProteinO75192 (Uniprot-TrEMBL)
PLIN2ProteinQ99541 (Uniprot-TrEMBL)
PPARA [nucleoplasm]ProteinQ07869 (Uniprot-TrEMBL)
PPARA:RXRA Coactivator ComplexComplexREACT_20439 (Reactome)
PPARA:RXRA HeterodimerComplexREACT_20362 (Reactome)
PPARA:RXRA Repressor ComplexComplexREACT_19814 (Reactome)
PPARAProteinQ07869 (Uniprot-TrEMBL)
PPARG [nucleoplasm]ProteinP37231 (Uniprot-TrEMBL)
PPARG:Fatty

Acid:RXRA:Mediator:Coactivator

Complex		ComplexREACT_27768 (Reactome)
PPARGC1A [nucleoplasm]ProteinQ9UBK2 (Uniprot-TrEMBL)
PPARGC1B [nucleoplasm]ProteinQ86YN6 (Uniprot-TrEMBL)
Palm [nucleoplasm]MetaboliteCHEBI:15756 (ChEBI)
Peroxisome

Proliferator Receptor Element

(PPRE)		REACT_20340 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
RGL1ProteinQ9NZL6 (Uniprot-TrEMBL)
RGZ [nucleoplasm]MetaboliteCHEBI:50122 (ChEBI)
ROR-alpha:CoactivatorComplexREACT_111748 (Reactome)
RORA [nucleoplasm]ProteinP35398 (Uniprot-TrEMBL)
RXRA [nucleoplasm]ProteinP19793 (Uniprot-TrEMBL)
RXRAProteinP19793 (Uniprot-TrEMBL)
SIN3A [nucleoplasm]ProteinQ96ST3 (Uniprot-TrEMBL)
SIN3B-1 [nucleoplasm]ProteinO75182-1 (Uniprot-TrEMBL)
SLC27A1ProteinQ6PCB7 (Uniprot-TrEMBL)
SMARCD3 [nucleoplasm]ProteinQ6STE5 (Uniprot-TrEMBL)
SP1(1-785) [nucleoplasm]ProteinP08047 (Uniprot-TrEMBL)
SREBF1-1(1-490) [nucleoplasm]ProteinP36956-1 (Uniprot-TrEMBL)
SREBF1-3 [nucleoplasm]ProteinP36956-3 (Uniprot-TrEMBL)
SREBF2(1-484) [nucleoplasm]ProteinQ12772 (Uniprot-TrEMBL)
SREBP1A/1C/2:NF-Y:HMGCS1 geneComplexREACT_148333 (Reactome)
SREBP1A/1C/2:NF-Y:SP1:FDFT1 geneComplexREACT_148107 (Reactome)
SREBP1A/2:NF-Y:HMGCR geneComplexREACT_148301 (Reactome)
SULT2A1(2-285)ProteinQ06520 (Uniprot-TrEMBL)
TBL1X [nucleoplasm]ProteinO60907 (Uniprot-TrEMBL)
TBL1XProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 [nucleoplasm]ProteinQ9BZK7 (Uniprot-TrEMBL)
TBL1XR1ProteinQ9BZK7 (Uniprot-TrEMBL)
TEAD1 [nucleoplasm]ProteinP28347 (Uniprot-TrEMBL)
TEAD2 [nucleoplasm]ProteinQ15562 (Uniprot-TrEMBL)
TEAD3(1-435) [nucleoplasm]ProteinQ99594 (Uniprot-TrEMBL)
TEAD4 [nucleoplasm]ProteinQ15561 (Uniprot-TrEMBL)
TEAD:WWTR1(TAZ)ComplexREACT_120065 (Reactome)
TEAD:YAP1ComplexREACT_119773 (Reactome)
TGS1 [nucleoplasm]ProteinQ96RS0 (Uniprot-TrEMBL)
TIAM2(2-1701)ProteinQ8IVF5 (Uniprot-TrEMBL)
TNFRSF21ProteinO75509 (Uniprot-TrEMBL)
TRIB3ProteinQ96RU7 (Uniprot-TrEMBL)
TXNRD1ProteinQ16881 (Uniprot-TrEMBL)
UGT1A9ProteinO60656 (Uniprot-TrEMBL)
WWTR1 [nucleoplasm]ProteinQ9GZV5 (Uniprot-TrEMBL)
YAP1 [nucleoplasm]ProteinP46937 (Uniprot-TrEMBL)
ferriheme b [nucleoplasm]MetaboliteCHEBI:36144 (ChEBI)
p-BMAL1:p-CLOCK/NPAS2:DNAComplexREACT_25790 (Reactome)
p-S-ARNTL [nucleoplasm]ProteinO00327 (Uniprot-TrEMBL)
p-S-CLOCK [nucleoplasm]ProteinO15516 (Uniprot-TrEMBL)
p-S-NPAS2 [nucleoplasm]ProteinQ99743 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
4xPalmC-CD36ArrowREACT_27168 (Reactome)
ABCA1ArrowREACT_115994 (Reactome)
ABCB4ArrowREACT_115807 (Reactome)
ACADMArrowREACT_116020 (Reactome)
ACOX1-1ArrowREACT_115624 (Reactome)
ACSL1ArrowREACT_115978 (Reactome)
AGTArrowREACT_115879 (Reactome)
ALAS1 gene:NRF1:PPARGC1BArrowREACT_115949 (Reactome)
ALAS1 gene:NRF1:PPARGC1BREACT_115949 (Reactome)
ALAS1ArrowREACT_115949 (Reactome)
ANGPTL4ArrowREACT_27173 (Reactome)
ANKRD1ArrowREACT_115878 (Reactome)
APOA1(25-266)ArrowREACT_116159 (Reactome)
APOA2(24-100)ArrowREACT_116133 (Reactome)
APOA5ArrowREACT_115631 (Reactome)
CPT1AArrowREACT_115644 (Reactome)
CPT2ArrowREACT_115927 (Reactome)
CTGFArrowREACT_116163 (Reactome)
CYP1A1ArrowREACT_116079 (Reactome)
CYP4A11ArrowREACT_115547 (Reactome)
CYP7A1ArrowREACT_115550 (Reactome)
Coactivators of PPARalphaREACT_19175 (Reactome)
Corepressors of PPARalphaArrowREACT_19175 (Reactome)
Corepressors of PPARalphaREACT_19283 (Reactome)
ESRRAArrowREACT_115949 (Reactome)
FABP1:Ligands of PPARAREACT_19175 (Reactome)
FABP1ArrowREACT_115721 (Reactome)
FABP1ArrowREACT_19175 (Reactome)
FADS1(1-444)ArrowREACT_115953 (Reactome)
FDFT1ArrowREACT_115945 (Reactome)
FHL2ArrowREACT_116040 (Reactome)
G0S2ArrowREACT_115967 (Reactome)
GLIPR1ArrowREACT_115533 (Reactome)
GRHL1ArrowREACT_115770 (Reactome)
HMGCR-1ArrowREACT_115997 (Reactome)
HMGCS1ArrowREACT_115739 (Reactome)
HMGCS2ArrowREACT_116136 (Reactome)
ME1ArrowREACT_115847 (Reactome)
NPAS2ArrowREACT_116112 (Reactome)
NR1D1 (REV-ERBA):heme:CorepressorTBarREACT_116112 (Reactome)
PEX11AArrowREACT_115962 (Reactome)
PLIN2ArrowREACT_115542 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115533 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115542 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115547 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115550 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115593 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115624 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115625 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115631 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115644 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115677 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115721 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115729 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115739 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115770 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115777 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115807 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115815 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115847 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115875 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115878 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115879 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115927 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115945 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115949 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115953 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115962 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115967 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115978 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115979 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115994 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_115997 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116020 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116040 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116079 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116112 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116133 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116136 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116159 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_116163 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_19175 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_25084 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_27168 (Reactome)
PPARA:RXRA Coactivator ComplexArrowREACT_27173 (Reactome)
PPARA:RXRA HeterodimerArrowREACT_19370 (Reactome)
PPARA:RXRA HeterodimerREACT_19283 (Reactome)
PPARA:RXRA Repressor ComplexArrowREACT_19283 (Reactome)
PPARA:RXRA Repressor ComplexREACT_19175 (Reactome)
PPARAArrowREACT_25084 (Reactome)
PPARAREACT_19370 (Reactome)
PPARG:Fatty

Acid:RXRA:Mediator:Coactivator

Complex		ArrowREACT_27168 (Reactome)
PPARG:Fatty

Acid:RXRA:Mediator:Coactivator

Complex		ArrowREACT_27173 (Reactome)
Peroxisome

Proliferator Receptor Element

(PPRE)		REACT_19370 (Reactome)
REACT_115533 (Reactome) The GLIPR1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115542 (Reactome) The Adipophilin (PLIN2) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115547 (Reactome) The CYP4A11 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115550 (Reactome) The CYP7A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115593 (Reactome) The TIAM2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115624 (Reactome) The ACOX1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115625 (Reactome) The RGL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115631 (Reactome) The APOA5 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115644 (Reactome) The CPT1A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115677 (Reactome) The TXNRD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115721 (Reactome) The FABP1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115729 (Reactome) The SULT2A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115739 (Reactome) The HMGCS1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115770 (Reactome) The GRHL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115777 (Reactome) The UGT1A9 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115807 (Reactome) The ABCB4 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115815 (Reactome) The TRIB3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115847 (Reactome) The ME1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115875 (Reactome) The TNFRSF21 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115878 (Reactome) The ANKRD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115879 (Reactome) The AGT gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115927 (Reactome) The CPT2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115945 (Reactome) The FDFT1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115949 (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.
REACT_115953 (Reactome) The FADS1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115962 (Reactome) The PEX11A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115967 (Reactome) The G0S2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115978 (Reactome) The ACSL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115979 (Reactome) The FATP1 (SLC27A1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115994 (Reactome) The ABCA1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_115997 (Reactome) The HMGCR gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116020 (Reactome) The ACADM gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116040 (Reactome) The FHL2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116079 (Reactome) The CYP1A1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116112 (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.
REACT_116133 (Reactome) The APOA2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116136 (Reactome) The HMGCS2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116159 (Reactome) The APOA1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
REACT_116163 (Reactome) The CTGF gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Transcription of the CTGF gene is increased by both YAP1:TEAD and WWTR1(TAZ):TEAD transcriptional coactivator:transcription factor complexes, so that CTFG is one of the many genes whose expression is downregulated by the action of the hippo cascade (Zhang et al. 2009; Zhao et al. 2008).
REACT_19175 (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.
REACT_19283 (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.
REACT_19370 (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.
REACT_25084 (Reactome) The PPARA gene is transcribed to yield mRNA and the mRNA is translated to yield protein. As inferred from mouse, BMAL1:CLOCK heterodimers bind the scond intron of the PPARA gene and activate transcription of PPARA.
REACT_27168 (Reactome) The Platelet glycoprotein IV gene (CD36, PAS IV, GPIV) is transcribed to yield mRNA and the mRNA is translated to yield proteind.
REACT_27173 (Reactome) The ANGPTL4 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
RGL1ArrowREACT_115625 (Reactome)
ROR-alpha:CoactivatorArrowREACT_115644 (Reactome)
ROR-alpha:CoactivatorArrowREACT_116112 (Reactome)
RXRAREACT_19370 (Reactome)
SLC27A1ArrowREACT_115979 (Reactome)
SREBP1A/1C/2:NF-Y:HMGCS1 geneArrowREACT_115739 (Reactome)
SREBP1A/1C/2:NF-Y:HMGCS1 geneREACT_115739 (Reactome)
SREBP1A/1C/2:NF-Y:SP1:FDFT1 geneArrowREACT_115945 (Reactome)
SREBP1A/1C/2:NF-Y:SP1:FDFT1 geneREACT_115945 (Reactome)
SREBP1A/2:NF-Y:HMGCR geneArrowREACT_115997 (Reactome)
SREBP1A/2:NF-Y:HMGCR geneREACT_115997 (Reactome)
SULT2A1(2-285)ArrowREACT_115729 (Reactome)
TBL1XR1REACT_19283 (Reactome)
TBL1XREACT_19283 (Reactome)
TEAD:WWTR1(TAZ)ArrowREACT_116163 (Reactome)
TEAD:YAP1ArrowREACT_116163 (Reactome)
TIAM2(2-1701)ArrowREACT_115593 (Reactome)
TNFRSF21ArrowREACT_115875 (Reactome)
TRIB3ArrowREACT_115815 (Reactome)
TXNRD1ArrowREACT_115677 (Reactome)
UGT1A9ArrowREACT_115777 (Reactome)
p-BMAL1:p-CLOCK/NPAS2:DNAArrowREACT_25084 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2797"
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