PPARA (peroxisome proliferator activated receptor alpha)

Gene

• Entrez ID: 5465
• Gene name: Peroxisome proliferator activated receptor alpha
• Gene symbol: PPARA
• Synonyms: NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR
• Chromosome: 22
• Chromosome location: 22q13.31
• Summary: Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1800206	C>G	Risk-factor	Coding sequence variant, non coding transcript variant, missense variant, synonymous variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000630	hsa-miR-519d-3p	Luciferase reporter assay, qRT-PCR, Western blot	20057369
MIRT002473	hsa-miR-22-3p	Western blot	18347104
MIRT002473	hsa-miR-22-3p	Luciferase reporter assay, qRT-PCR, Western blot	19011694
MIRT005068	hsa-miR-10b-5p	Luciferase reporter assay, qRT-PCR, Western blot	19780876
MIRT006422	hsa-miR-21-5p	Luciferase reporter assay, Flow, Immunoprecipitaion, In situ hybridization, qRT-PCR, Western blot	21636785
MIRT006422	hsa-miR-21-5p	Microarray	18591254
MIRT006422	hsa-miR-21-5p	Immunofluorescence, Immunohistochemistry, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	24012640
MIRT006422	hsa-miR-21-5p	qRT-PCR, Western blot	26338827
MIRT006709	hsa-miR-141-3p	Luciferase reporter assay, qRT-PCR, Western blot	22479552
MIRT017974	hsa-miR-335-5p	Microarray	18185580
MIRT022715	hsa-miR-124-3p	Microarray	18668037
MIRT053098	hsa-miR-9-5p	Luciferase reporter assay	23525285
MIRT054795	hsa-miR-548d-5p	Luciferase reporter assay, QRTPCR, Western blotting	24929254
MIRT158798	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT158799	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT206051	hsa-miR-519c-3p	HITS-CLIP	23824327
MIRT437434	hsa-miR-33a-5p	qRT-PCR, Western blot	24100264
MIRT438762	hsa-miR-130a-3p	Luciferase reporter assay	24960162
MIRT445022	hsa-miR-27a-5p	PAR-CLIP	22100165
MIRT445022	hsa-miR-27a-5p	Luciferase reporter assay, Western blot	27910957
MIRT445023	hsa-miR-4699-5p	PAR-CLIP	22100165
MIRT445024	hsa-miR-4662b	PAR-CLIP	22100165
MIRT445025	hsa-miR-4647	PAR-CLIP	22100165
MIRT445026	hsa-miR-4426	PAR-CLIP	22100165
MIRT454319	hsa-miR-6788-5p	PAR-CLIP	23592263
MIRT454321	hsa-miR-30c-2-3p	PAR-CLIP	23592263
MIRT454322	hsa-miR-5006-5p	PAR-CLIP	23592263
MIRT454323	hsa-miR-30c-1-3p	PAR-CLIP	23592263
MIRT454324	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT454325	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT454326	hsa-miR-8085	PAR-CLIP	23592263
MIRT454327	hsa-miR-6731-5p	PAR-CLIP	23592263
MIRT454328	hsa-miR-6878-5p	PAR-CLIP	23592263
MIRT454329	hsa-miR-6851-5p	PAR-CLIP	23592263
MIRT454330	hsa-miR-3689d	PAR-CLIP	23592263
MIRT454331	hsa-miR-6797-5p	PAR-CLIP	23592263
MIRT454332	hsa-miR-4755-3p	PAR-CLIP	23592263
MIRT454333	hsa-miR-1249-5p	PAR-CLIP	23592263
MIRT454334	hsa-miR-4459	PAR-CLIP	23592263
MIRT454335	hsa-miR-6757-5p	PAR-CLIP	23592263
MIRT454336	hsa-miR-4779	PAR-CLIP	23592263
MIRT609980	hsa-miR-6089	HITS-CLIP	23824327
MIRT609981	hsa-miR-129-5p	HITS-CLIP	23824327
MIRT609982	hsa-miR-608	HITS-CLIP	23824327
MIRT609983	hsa-miR-4651	HITS-CLIP	23824327
MIRT615378	hsa-miR-6766-5p	HITS-CLIP	23824327
MIRT615379	hsa-miR-6756-5p	HITS-CLIP	23824327
MIRT640600	hsa-miR-335-3p	HITS-CLIP	23824327
MIRT640600	hsa-miR-335-3p	HITS-CLIP	27418678
MIRT640601	hsa-miR-1305	HITS-CLIP	23824327
MIRT640601	hsa-miR-1305	HITS-CLIP	27418678
MIRT640602	hsa-miR-607	HITS-CLIP	23824327
MIRT640603	hsa-miR-4753-3p	HITS-CLIP	23824327
MIRT640603	hsa-miR-4753-3p	HITS-CLIP	27418678
MIRT640604	hsa-miR-3671	HITS-CLIP	23824327
MIRT640604	hsa-miR-3671	HITS-CLIP	27418678
MIRT640605	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT640605	hsa-miR-130b-5p	HITS-CLIP	27418678
MIRT640606	hsa-miR-5692a	HITS-CLIP	23824327
MIRT640606	hsa-miR-5692a	HITS-CLIP	27418678
MIRT732545	hsa-miR-34a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26330104
MIRT733074	hsa-miR-9-3p	Luciferase reporter assay, qRT-PCR, Western blot	25592151
MIRT733266	hsa-miR-130b-3p	qRT-PCR, Western blot	26475357
MIRT733266	hsa-miR-130b-3p	Luciferase reporter assay	27364335
MIRT733437	hsa-miR-196b-5p	Next Generation Sequencing (NGS), qRT-PCR	28272430

Transcription factors

Transcription factor	Regulation	Reference
CREBBP	Unknown	10542237
HIF1A	Unknown	14521756
HNF4A	Unknown	11981036
JUN	Unknown	10542237
NR2F2	Unknown	11981036
RELA	Unknown	10542237
STAT1	Activation	24242046
STAT3	Activation	24242046
TP63	Unknown	19458633

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	9748239, 12700342
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	9748239
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001103	Function	RNA polymerase II repressing transcription factor binding	IBA	21873635
GO:0001103	Function	RNA polymerase II repressing transcription factor binding	IPI	19955185
GO:0001223	Function	Transcription coactivator binding	IEA
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IBA	21873635
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA	9748239
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	9748239
GO:0001666	Process	Response to hypoxia	IEA
GO:0003677	Function	DNA binding	TAS	10860941
GO:0003700	Function	DNA-binding transcription factor activity	IDA	19955185
GO:0003700	Function	DNA-binding transcription factor activity	ISS
GO:0003707	Function	Steroid hormone receptor activity	IDA	19955185
GO:0004879	Function	Nuclear receptor activity	IBA	21873635
GO:0004879	Function	Nuclear receptor activity	IDA	12955147, 19955185
GO:0005515	Function	Protein binding	IPI	9653119, 11915042, 16554032, 19955185, 21775429, 24043310, 24713062, 25814554, 32814053
GO:0005634	Component	Nucleus	IDA	24639097
GO:0005634	Component	Nucleus	TAS	16271724
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0006631	Process	Fatty acid metabolic process	IBA	21873635
GO:0007507	Process	Heart development	IEA
GO:0008134	Function	Transcription factor binding	IPI	26504087
GO:0008144	Function	Drug binding	IDA	12955147
GO:0008270	Function	Zinc ion binding	IEA
GO:0008289	Function	Lipid binding	IDA	12955147
GO:0008544	Process	Epidermis development	IEA
GO:0009267	Process	Cellular response to starvation	ISS
GO:0009755	Process	Hormone-mediated signaling pathway	IBA	21873635
GO:0010565	Process	Regulation of cellular ketone metabolic process	IDA	19955185
GO:0010745	Process	Negative regulation of macrophage derived foam cell differentiation	IC	12700342
GO:0010745	Process	Negative regulation of macrophage derived foam cell differentiation	IDA	19114110
GO:0010876	Process	Lipid localization	IEA
GO:0010887	Process	Negative regulation of cholesterol storage	IBA	21873635
GO:0010887	Process	Negative regulation of cholesterol storage	IDA	19114110
GO:0010891	Process	Negative regulation of sequestering of triglyceride	IDA	12700342
GO:0019216	Process	Regulation of lipid metabolic process	IBA	21873635
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0019217	Process	Regulation of fatty acid metabolic process	IDA	19955185
GO:0019902	Function	Phosphatase binding	IEA
GO:0019904	Function	Protein domain specific binding	IEA
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	IDA	31611175
GO:0030522	Process	Intracellular receptor signaling pathway	IEA
GO:0031624	Function	Ubiquitin conjugating enzyme binding	IPI	19955185
GO:0032000	Process	Positive regulation of fatty acid beta-oxidation	TAS	16271724
GO:0032091	Process	Negative regulation of protein binding	IEA
GO:0032099	Process	Negative regulation of appetite	ISS
GO:0032868	Process	Response to insulin	IEA
GO:0032922	Process	Circadian regulation of gene expression	ISS
GO:0033993	Process	Response to lipid	IBA	21873635
GO:0035095	Process	Behavioral response to nicotine	IEA
GO:0042060	Process	Wound healing	IEA
GO:0042157	Process	Lipoprotein metabolic process	IEA
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0043401	Process	Steroid hormone mediated signaling pathway	IEA
GO:0043565	Function	Sequence-specific DNA binding	ISS
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045070	Process	Positive regulation of viral genome replication	IMP	22479552
GO:0045471	Process	Response to ethanol	IEA
GO:0045722	Process	Positive regulation of gluconeogenesis	IEA
GO:0045776	Process	Negative regulation of blood pressure	IEA
GO:0045820	Process	Negative regulation of glycolytic process	IDA	19955185
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	12955147
GO:0045923	Process	Positive regulation of fatty acid metabolic process	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9748239, 19955185, 20837115
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046321	Process	Positive regulation of fatty acid oxidation	ISS
GO:0046889	Process	Positive regulation of lipid biosynthetic process	IMP	25592151
GO:0050728	Process	Negative regulation of inflammatory response	IBA	21873635
GO:0050728	Process	Negative regulation of inflammatory response	IDA	21636785
GO:0051525	Function	NFAT protein binding	IEA
GO:0051898	Process	Negative regulation of protein kinase B signaling	IMP	31574452
GO:0061052	Process	Negative regulation of cell growth involved in cardiac muscle cell development	IEA
GO:0070166	Process	Enamel mineralization	IEA
GO:0097371	Function	MDM2/MDM4 family protein binding	IEA
GO:1900016	Process	Negative regulation of cytokine production involved in inflammatory response	IMP	31574452
GO:1901215	Process	Negative regulation of neuron death	IEA
GO:1902894	Process	Negative regulation of pri-miRNA transcription by RNA polymerase II	IDA	21636785
GO:1903038	Process	Negative regulation of leukocyte cell-cell adhesion	IDA	21636785
GO:1903427	Process	Negative regulation of reactive oxygen species biosynthetic process	IMP	31574452
GO:1903944	Process	Negative regulation of hepatocyte apoptotic process	IMP	31574452
GO:2000191	Process	Regulation of fatty acid transport	TAS	16271724
GO:2000272	Process	Negative regulation of signaling receptor activity	IDA	12700342
GO:2001171	Process	Positive regulation of ATP biosynthetic process	IMP	31574452

Other IDs

• MIM: 170998
• HGNC: 9232
• e!Ensembl: ENSG00000186951

Protein

• UniProt ID: Q07869
• Protein name: Peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Nuclear receptor subfamily 1 group C member 1)
• Protein function: Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
• PDB: 1I7G, 1K7L, 1KKQ, 2NPA, 2P54, 2REW, 2ZNN, 3ET1, 3FEI, 3G8I, 3KDT, 3KDU, 3SP6, 3VI8, 4BCR, 4CI4, 5AZT, 5HYK, 6KAX, 6KAY, 6KAZ, 6KB0, 6KB1, 6KB2, 6KB3, 6KB4, 6KB5, 6KB6, 6KB7, 6KB8, 6KB9, 6KBA, 6KXX, 6KXY, 6KYP, 6L36, 6L37, 6L38, 6L96, 6LX4, 6LX5, 6LX6, 6LX7, 6LX8, 6LX9, 6LXA, 6LXB, 6LXC, 7BPY, 7BPZ, 7BQ0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00105	zf-C4	100 → 168	Zinc finger, C4 type (two domains)	Domain
  PF00104	Hormone_recep	264 → 449	Ligand-binding domain of nuclear hormone receptor	Domain

• Sequence:

  MVDTESPLCPLSPLEAGDLESPLSEEFLQEMGNIQEISQSIGEDSSGSFGFTEYQYLGSC
  PGSDGSVITDTLSPASSPSSVTYPVVPGSVDESPSGALNIECRICGDKASGYHYGVHACE
  GCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGMSHNAIRFGRMPRSE
  KAKLKAEILTCEHDIEDSETADLKSLAKRIYEAYLKNFNMNKVKARVILSGKASNNPPFV
  IHDMETLCMAEKTLVAKLVANGIQNKEAEVRIFHCCQCTSVETVTELTEFAKAIPGFANL
  DLNDQVTLLKYGVYEAIFAMLSSVMNKDGMLVAYGNGFITREFLKSLRKPFCDIMEPKFD
  FAMKFNALELDDSDISLFVAAIICCGDRPGLLNVGHIEKMQEGIVHVLRLHLQSNHPDDI
  FLFPKLLQKMADLRQLVTEHAQLVQIIKKTESDAALHPLLQEIYRDMY

• Sequence length: 468