Regulation of lipid metabolism by PPARalpha (Homo sapiens)

From WikiPathways

Revision as of 11:39, 10 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
9, 13, 33, 424720, 371420, 47472, 7, 9, 10, 12...7-9, 13, 33...204202020, 472020, 27203, 7, 9, 13, 33...30, 31476, 2016202020, 47472019, 20, 274739202146, 474729224320, 472017, 4936205, 26, 472020, 352020, 47nucleoplasmSREBP1A/1C/2NF-YSP1FDFT1 gene SREBF1A,1C,2 cleaved by S2P PPARARXRA Repressor Complex TEADWWTR1Coactivators of PPARalpha PPARGFatty AcidRXRAMediatorCoactivator Complex FABP1Ligands of PPARA Ligands of PPARA NF-Y mitochondrial matrixCorepressors of PPARalpha SREBP1A/1C/2 Dimer TEADYAP1 SREBF1A,1C,2 cleaved by S2P TEAD ROR-alphaCoactivator Ligands of PPARA PPARARXRA Heterodimer NF-Y SREBF1A,2 lipid particleALAS1 geneNRF1PPARGC1B peroxisomal matrixNF-Y endoplasmic reticulum membraneActivated PPARGRXRA TEAD NR1D1 PPARARXRA Coactivator Complex PPARARXRA Heterodimer PPARA Fatty Acid Complex SREBP1A/1C/2 Dimer Ligands of PPARG PPARGFatty Acid Ligand p-CLOCK/p-NPAS2 mitochondrial outer membraneMediator Complex SREBP1A/1C/2NF-YHMGCS1 gene SREBP1A/2 Dimer NR1D1 Activated PPARARXRA Heterodimer cytosolSREBP1A/2NF-YHMGCR gene p-BMAL1p-CLOCK/NPAS2DNA NFYA PPARARXRA Repressor ComplexG0S2FABP1 CPT1AMED30MED26 CHD9 Peroxisome Proliferator Receptor Element FDFT1 gene CTGFNCOA6 ESRRATEAD1 APOA1ALA TEAD3TEAD4 PPARGC1A ME1NR1D1 PPARA PPARARXRA Coactivator ComplexMED22 PPARGC1B TEAD4 TBL1XR1 LINA TBL1X TBL1X RORA MED10RGZ ACOX1-14xPalmC-CD36EPA RXRA HDAC3 NFYC EPA NFYB CREBBPABCA1PEX11AANKRD1AA RXRA WWTR1 SIN3B-1 MED13 ferriheme b NCOA2 TEAD1 ANGPTL4HMGCR-1ALAS1 geneNRF1PPARGC1BSULT2A1MED24 MED6 CDK19 FHL2SMARCD3 MED7 ROR-alphaCoactivatorFADS1ALA 9S-HODE MED8 TBL1XR1 Corepressors of PPARalphaSREBP1A/2NF-YHMGCR geneTBL1XR1ALAS1CYP1A1HMGCS2SREBF1-1TGS1 TEADYAP1APOA5NCOA1 MED25 MED1 EP300HMGCS1SP1NCOA2 MED14 ACSL1HELZ2 PPARGFatty AcidRXRAMediatorCoactivator ComplexTXNRD1LINA p-BMAL1p-CLOCK/NPAS2DNAHMGCR gene MED4 NRF1 Coactivators of PPARalphaSREBF1-1NFYC MED13L NFYC NCOR1 MED20 MED9 MED17 NCOR1 MED16 Palm CYP7A1AA TBL1XPalm NR1D1 MED11 PPARA PPARG SREBF1-1PPARGC1A HELZ2 HDAC3 ALAS1 gene SREBF2HMGCS1 gene NFYA GRHL1SREBP1A/1C/2NF-YSP1FDFT1 geneActos SREBF1-3 NCOR2 TEAD2 FDFT1CDK8 p-S-NPAS2 MED19 MED1 SREBF1-3 RXRA CCNC CYP4A11ACADMMED21 MED18 RXRAEP300MED15 TRIB3NPAS2PPARANCOA3 AGTSIN3A p-S-ARNTL TEAD2 RGL1PPARARXRA HeterodimerTEADWWTR1PPARA GLIPR1TNFRSF21TIAM2RXRA SLC27A1UGT1A9APOA213NFYA PLIN2MED29CARM1SREBF2MED31 p-S-CLOCK CREBBPSREBP1A/1C/2NF-YHMGCS1 geneMED23 YAP1 MED12 NFYB TEAD3NFYB ABCB4CPT2SREBF2NCOA1 MED27 FABP1Ligands of PPARAFABP1321, 1825, 385, 2624, 414552, 2345401, 18154511, 34, 442, 23


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

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Hua F, Mu R, Liu J, Xue J, Wang Z, Lin H, Yang H, Chen X, Hu Z.; ''TRB3 interacts with SMAD3 promoting tumor cell migration and invasion.''; PubMed Europe PMC Scholia
  2. Vock C, Döring F, Nitz I.; ''Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP.''; PubMed Europe PMC Scholia
  3. Guo L, Guo ZX, Gong HP, Shang YY, Zhong M, Zhang Y, Zhang W.; ''Tribbles homolog 3 is induced by high glucose and associated with apoptosis in human endothelial cells.''; PubMed Europe PMC Scholia
  4. Haarmann-Stemmann T, Abel J.; ''The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function.''; PubMed Europe PMC Scholia
  5. Krey G, Braissant O, L'Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W.; ''Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay.''; PubMed Europe PMC Scholia
  6. Mukherjee R, Jow L, Noonan D, McDonnell DP.; ''Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators.''; PubMed Europe PMC Scholia
  7. Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C.; ''Peroxisome proliferator-activated receptor alpha (PPARalpha ) turnover by the ubiquitin-proteasome system controls the ligand-induced expression level of its target genes.''; PubMed Europe PMC Scholia
  8. Krammer J, Digel M, Ehehalt F, Stremmel W, Füllekrug J, Ehehalt R.; ''Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells.''; PubMed Europe PMC Scholia
  9. Amemiya-Kudo M, Shimano H, Hasty AH, Yahagi N, Yoshikawa T, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Sato R, Kimura S, Ishibashi S, Yamada N.; ''Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes.''; PubMed Europe PMC Scholia
  10. Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W.; ''From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions.''; PubMed Europe PMC Scholia
  11. Bardot O, Aldridge TC, Latruffe N, Green S.; ''PPAR-RXR heterodimer activates a peroxisome proliferator response element upstream of the bifunctional enzyme gene.''; PubMed Europe PMC Scholia
  12. Xu J, Lv S, Qin Y, Shu F, Xu Y, Chen J, Xu BE, Sun X, Wu J.; ''TRB3 interacts with CtIP and is overexpressed in certain cancers.''; PubMed Europe PMC Scholia
  13. van der Meer DL, Degenhardt T, Väisänen S, de Groot PJ, Heinäniemi M, de Vries SC, Müller M, Carlberg C, Kersten S.; ''Profiling of promoter occupancy by PPARalpha in human hepatoma cells via ChIP-chip analysis.''; PubMed Europe PMC Scholia
  14. Hahn ME, Allan LL, Sherr DH.; ''Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor.''; PubMed Europe PMC Scholia
  15. Wolfrum C, Borrmann CM, Borchers T, Spener F.; ''Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha - and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus.''; PubMed Europe PMC Scholia
  16. Rakhshandehroo M, Hooiveld G, Müller M, Kersten S.; ''Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.''; PubMed Europe PMC Scholia
  17. Zheng J, Shan Y, Lambrecht RW, Donohue SE, Bonkovsky HL.; ''Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt protoporphyrin.''; PubMed Europe PMC Scholia
  18. Roberts AG, Elder GH.; ''Alternative splicing and tissue-specific transcription of human and rodent ubiquitous 5-aminolevulinate synthase (ALAS1) genes.''; PubMed Europe PMC Scholia
  19. Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH.; ''The aryl hydrocarbon receptor complex and the control of gene expression.''; PubMed Europe PMC Scholia
  20. Jiang G, McKenzie TL, Conrad DG, Shechter I.; ''Transcriptional regulation by lovastatin and 25-hydroxycholesterol in HepG2 cells and molecular cloning and expression of the cDNA for the human hepatic squalene synthase.''; PubMed Europe PMC Scholia
  21. Johnson EF, Hsu MH, Savas U, Griffin KJ.; ''Regulation of P450 4A expression by peroxisome proliferator activated receptors.''; PubMed Europe PMC Scholia
  22. Qi C, Zhu Y, Reddy JK.; ''Peroxisome proliferator-activated receptors, coactivators, and downstream targets.''; PubMed Europe PMC Scholia
  23. Shimamoto Y, Hirota K, Fukamizu A.; ''Effect of peroxisome proliferator-activated receptor alpha on human angiotensinogen promoter.''; PubMed Europe PMC Scholia
  24. Barbier O, Villeneuve L, Bocher V, Fontaine C, Torra IP, Duhem C, Kosykh V, Fruchart JC, Guillemette C, Staels B.; ''The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene.''; PubMed Europe PMC Scholia
  25. Tian L, Zhou J, Casimiro MC, Liang B, Ojeifo JO, Wang M, Hyslop T, Wang C, Pestell RG.; ''Activating peroxisome proliferator-activated receptor gamma mutant promotes tumor growth in vivo by enhancing angiogenesis.''; PubMed Europe PMC Scholia
  26. Yang X, Lu X, Lombès M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J.; ''The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase.''; PubMed Europe PMC Scholia
  27. Kersten S.; ''Peroxisome proliferator activated receptors and lipoprotein metabolism.''; PubMed Europe PMC Scholia
  28. Knutti D, Kaul A, Kralli A.; ''A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen.''; PubMed Europe PMC Scholia
  29. Zhou YD, Barnard M, Tian H, Li X, Ring HZ, Francke U, Shelton J, Richardson J, Russell DW, McKnight SL.; ''Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.''; PubMed Europe PMC Scholia
  30. Vallett SM, Sanchez HB, Rosenfeld JM, Osborne TF.; ''A direct role for sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene.''; PubMed Europe PMC Scholia
  31. Gouni-Berthold I, Krone W.; ''Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis.''; PubMed Europe PMC Scholia
  32. Perissi V, Aggarwal A, Glass CK, Rose DW, Rosenfeld MG.; ''A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors.''; PubMed Europe PMC Scholia
  33. Mochizuki K, Suruga K, Fukami H, Kiso Y, Takase S, Goda T.; ''Selectivity of fatty acid ligands for PPARalpha which correlates both with binding to cis-element and DNA binding-independent transactivity in Caco-2 cells.''; PubMed Europe PMC Scholia
  34. Britton CH, Schultz RA, Zhang B, Esser V, Foster DW, McGarry JD.; ''Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.''; PubMed Europe PMC Scholia
  35. Fang HL, Strom SC, Cai H, Falany CN, Kocarek TA, Runge-Morris M.; ''Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor.''; PubMed Europe PMC Scholia
  36. Yu S, Reddy JK.; ''Transcription coactivators for peroxisome proliferator-activated receptors.''; PubMed Europe PMC Scholia
  37. Matsumura R, Matsubara C, Node K, Takumi T, Akashi M.; ''Nuclear receptor-mediated cell-autonomous oscillatory expression of the circadian transcription factor, neuronal PAS domain protein 2 (NPAS2).''; PubMed Europe PMC Scholia
  38. Cheema SK, Agellon LB.; ''The murine and human cholesterol 7alpha-hydroxylase gene promoters are differentially responsive to regulation by fatty acids mediated via peroxisome proliferator-activated receptor alpha.''; PubMed Europe PMC Scholia
  39. Crumbley C, Wang Y, Kojetin DJ, Burris TP.; ''Characterization of the core mammalian clock component, NPAS2, as a REV-ERBalpha/RORalpha target gene.''; PubMed Europe PMC Scholia
  40. Lu X, Yang X, Liu J.; ''Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2.''; PubMed Europe PMC Scholia
  41. Vu-Dac N, Chopin-Delannoy S, Gervois P, Bonnelye E, Martin G, Fruchart JC, Laudet V, Staels B.; ''The nuclear receptors peroxisome proliferator-activated receptor alpha and Rev-erbalpha mediate the species-specific regulation of apolipoprotein A-I expression by fibrates.''; PubMed Europe PMC Scholia
  42. Wang M, Yang F, Zhang X, Zhao H, Wang Q, Pan Y.; ''Comparative analysis of MTF-1 binding sites between human and mouse.''; PubMed Europe PMC Scholia
  43. Desvergne B, Wahli W.; ''Peroxisome proliferator-activated receptors: nuclear control of metabolism.''; PubMed Europe PMC Scholia
  44. Hostetler HA, McIntosh AL, Atshaves BP, Storey SM, Payne HR, Kier AB, Schroeder F.; ''L-FABP directly interacts with PPARalpha in cultured primary hepatocytes.''; PubMed Europe PMC Scholia
  45. Reed BD, Charos AE, Szekely AM, Weissman SM, Snyder M.; ''Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes.''; PubMed Europe PMC Scholia
  46. Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, Desvergne B.; ''DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.''; PubMed Europe PMC Scholia
  47. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM.; ''A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.''; PubMed Europe PMC Scholia
  48. Jakobsson T, Venteclef N, Toresson G, Damdimopoulos AE, Ehrlund A, Lou X, Sanyal S, Steffensen KR, Gustafsson JA, Treuter E.; ''GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus.''; PubMed Europe PMC Scholia
  49. Perera RJ, Marcusson EG, Koo S, Kang X, Kim Y, White N, Dean NM.; ''Identification of novel PPARgamma target genes in primary human adipocytes.''; PubMed Europe PMC Scholia
  50. Schachtrup C, Emmler T, Bleck B, Sandqvist A, Spener F.; ''Functional analysis of peroxisome-proliferator-responsive element motifs in genes of fatty acid-binding proteins.''; PubMed Europe PMC Scholia
  51. Tao N, Wagner SJ, Lublin DM.; ''CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.''; PubMed Europe PMC Scholia
  52. Liu MH, Li J, Shen P, Husna B, Tai ES, Yong EL.; ''A natural polymorphism in peroxisome proliferator-activated receptor-alpha hinge region attenuates transcription due to defective release of nuclear receptor corepressor from chromatin.''; PubMed Europe PMC Scholia

History

View all...
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
13MetaboliteCHEBI:34154 (ChEBI)
4xPalmC-CD36ProteinP16671 (Uniprot-TrEMBL)
9S-HODE MetaboliteCHEBI:34496 (ChEBI)
AA MetaboliteCHEBI:15843 (ChEBI)
ABCA1ProteinO95477 (Uniprot-TrEMBL)
ABCB4ProteinP21439 (Uniprot-TrEMBL)
ACADMProteinP11310 (Uniprot-TrEMBL)
ACOX1-1ProteinQ15067-1 (Uniprot-TrEMBL)
ACSL1ProteinP33121 (Uniprot-TrEMBL)
AGTProteinP01019 (Uniprot-TrEMBL)
ALA MetaboliteCHEBI:27432 (ChEBI)
ALAS1 gene

NRF1

PPARGC1B		ComplexREACT_151863 (Reactome)
ALAS1 gene ProteinENSG00000023330 (ENSEMBL)
ALAS1ProteinP13196 (Uniprot-TrEMBL)
ANGPTL4ProteinQ9BY76 (Uniprot-TrEMBL)
ANKRD1ProteinQ15327 (Uniprot-TrEMBL)
APOA1ProteinP02647 (Uniprot-TrEMBL)
APOA2ProteinP02652 (Uniprot-TrEMBL)
APOA5ProteinQ6Q788 (Uniprot-TrEMBL)
Actos MetaboliteCHEBI:8228 (ChEBI)
CARM1ProteinQ86X55 (Uniprot-TrEMBL)
CCNC ProteinP24863 (Uniprot-TrEMBL)
CDK19 ProteinQ9BWU1 (Uniprot-TrEMBL)
CDK8 ProteinP49336 (Uniprot-TrEMBL)
CHD9 ProteinQ3L8U1 (Uniprot-TrEMBL)
CPT1AProteinP50416 (Uniprot-TrEMBL)
CPT2ProteinP23786 (Uniprot-TrEMBL)
CREBBPProteinQ92793 (Uniprot-TrEMBL)
CTGFProteinP29279 (Uniprot-TrEMBL)
CYP1A1ProteinP04798 (Uniprot-TrEMBL)
CYP4A11ProteinQ02928 (Uniprot-TrEMBL)
CYP7A1ProteinP22680 (Uniprot-TrEMBL)
Coactivators of PPARalphaProteinREACT_20313 (Reactome)
Corepressors of PPARalphaProteinREACT_19786 (Reactome)
EP300ProteinQ09472 (Uniprot-TrEMBL)
EPA MetaboliteCHEBI:28364 (ChEBI)
ESRRAProteinP11474 (Uniprot-TrEMBL)
FABP1 Ligands of PPARAComplexREACT_119390 (Reactome)
FABP1 ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FABP1ProteinP07148 (Uniprot-TrEMBL) As inferred from mouse, FABP1 localizes to the nucleus where it may deliver lipids to PPARA.
FADS1ProteinO60427 (Uniprot-TrEMBL)
FDFT1 gene ProteinENSG00000079459 (ENSEMBL)
FDFT1ProteinP37268 (Uniprot-TrEMBL)
FHL2ProteinQ14192 (Uniprot-TrEMBL)
G0S2ProteinP27469 (Uniprot-TrEMBL)
GLIPR1ProteinP48060 (Uniprot-TrEMBL)
GRHL1ProteinQ9NZI5 (Uniprot-TrEMBL)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HELZ2 ProteinQ9BYK8 (Uniprot-TrEMBL)
HMGCR gene ProteinENSG00000113161 (ENSEMBL)
HMGCR-1ProteinP04035-1 (Uniprot-TrEMBL)
HMGCS1 gene ProteinENSG00000112972 (ENSEMBL)
HMGCS1ProteinQ01581 (Uniprot-TrEMBL)
HMGCS2ProteinP54868 (Uniprot-TrEMBL)
LINA MetaboliteCHEBI:17351 (ChEBI)
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.
MED10ProteinQ9BTT4 (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)
MED29ProteinQ9NX70 (Uniprot-TrEMBL)
MED30ProteinQ96HR3 (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)
NCOA1 ProteinQ15788 (Uniprot-TrEMBL)
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)
NPAS2ProteinQ99743 (Uniprot-TrEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 ComplexREACT_111441 (Reactome)
NRF1 ProteinQ16656 (Uniprot-TrEMBL)
PEX11AProteinO75192 (Uniprot-TrEMBL)
PLIN2ProteinQ99541 (Uniprot-TrEMBL)
PPARA RXRA Coactivator ComplexComplexREACT_20439 (Reactome)
PPARA RXRA HeterodimerComplexREACT_20362 (Reactome)
PPARA RXRA Repressor ComplexComplexREACT_19814 (Reactome)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARAProteinQ07869 (Uniprot-TrEMBL)
PPARG

Fatty Acid RXRA Mediator

Coactivator Complex		ComplexREACT_27768 (Reactome)
PPARG ProteinP37231 (Uniprot-TrEMBL)
PPARGC1A ProteinQ9UBK2 (Uniprot-TrEMBL)
PPARGC1B ProteinQ86YN6 (Uniprot-TrEMBL)
Palm MetaboliteCHEBI:15756 (ChEBI)
Peroxisome Proliferator Receptor Element 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 MetaboliteCHEBI:50122 (ChEBI)
ROR-alpha CoactivatorComplexREACT_111748 (Reactome)
RORA ProteinP35398 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
RXRAProteinP19793 (Uniprot-TrEMBL)
SIN3A ProteinQ96ST3 (Uniprot-TrEMBL)
SIN3B-1 ProteinO75182-1 (Uniprot-TrEMBL)
SLC27A1ProteinQ6PCB7 (Uniprot-TrEMBL)
SMARCD3 ProteinQ6STE5 (Uniprot-TrEMBL)
SP1ProteinP08047 (Uniprot-TrEMBL)
SREBF1-1ProteinP36956-1 (Uniprot-TrEMBL)
SREBF1-3 ProteinP36956-3 (Uniprot-TrEMBL)
SREBF2ProteinQ12772 (Uniprot-TrEMBL)
SREBP1A/1C/2

NF-Y

HMGCS1 gene		ComplexREACT_148333 (Reactome)
SREBP1A/1C/2

NF-Y SP1

FDFT1 gene		ComplexREACT_148107 (Reactome)
SREBP1A/2

NF-Y

HMGCR gene		ComplexREACT_148301 (Reactome)
SULT2A1ProteinQ06520 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (Uniprot-TrEMBL)
TBL1XR1ProteinQ9BZK7 (Uniprot-TrEMBL)
TEAD WWTR1ComplexREACT_120065 (Reactome)
TEAD YAP1ComplexREACT_119773 (Reactome)
TEAD1 ProteinP28347 (Uniprot-TrEMBL)
TEAD2 ProteinQ15562 (Uniprot-TrEMBL)
TEAD3ProteinQ99594 (Uniprot-TrEMBL)
TEAD4 ProteinQ15561 (Uniprot-TrEMBL)
TGS1 ProteinQ96RS0 (Uniprot-TrEMBL)
TIAM2ProteinQ8IVF5 (Uniprot-TrEMBL)
TNFRSF21ProteinO75509 (Uniprot-TrEMBL)
TRIB3ProteinQ96RU7 (Uniprot-TrEMBL)
TXNRD1ProteinQ16881 (Uniprot-TrEMBL)
UGT1A9ProteinO60656 (Uniprot-TrEMBL)
WWTR1 ProteinQ9GZV5 (Uniprot-TrEMBL)
YAP1 ProteinP46937 (Uniprot-TrEMBL)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
p-BMAL1

p-CLOCK/NPAS2

DNA		ComplexREACT_25790 (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
ALAS1 gene

NRF1

PPARGC1B		ArrowREACT_115949 (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_19175 (Reactome)
NR1D1 TBarREACT_116112 (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 HeterodimerREACT_19283 (Reactome)
PPARA RXRA Repressor ComplexREACT_19175 (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 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.
ROR-alpha CoactivatorArrowREACT_115644 (Reactome)
ROR-alpha CoactivatorArrowREACT_116112 (Reactome)
RXRAREACT_19370 (Reactome)
SREBP1A/1C/2

NF-Y

HMGCS1 gene		ArrowREACT_115739 (Reactome)
SREBP1A/1C/2

NF-Y SP1

FDFT1 gene		ArrowREACT_115945 (Reactome)
SREBP1A/2

NF-Y

HMGCR gene		ArrowREACT_115997 (Reactome)
TBL1XR1REACT_19283 (Reactome)
TBL1XREACT_19283 (Reactome)
TEAD WWTR1ArrowREACT_116163 (Reactome)
TEAD YAP1ArrowREACT_116163 (Reactome)
p-BMAL1

p-CLOCK/NPAS2

DNA		ArrowREACT_25084 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2797"
Personal tools