P37230 (PPARA_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome proliferator-activated receptor alpha
Short name=PPAR-alpha

Alternative name(s):
Nuclear receptor subfamily 1 group C member 1

Gene names

Name:	Ppara
Synonyms:	Nr1c1, Ppar

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity. 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 By similarity.
Subunit structure	Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity By similarity. Interacts with AKAP13, LPIN1 and PRDM16. Also interacts with PPARBP coactivator in vitro. Interacts with NCOA3 and NCOA6 coactivators By similarity. Interacts with CITED2; the interaction stimulates its transcriptional activity. Interacts with ASXL1 AND ASXL2 By similarity. Ref.3
Subcellular location	Nucleus.
Tissue specificity	Expressed predominantly in liver and kidney.
Post-translational modification	Phosphorylated. Ref.2
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to nicotine Inferred from direct assay PubMed 20801430. Source: RGD enamel mineralization Inferred from electronic annotation. Source: Compara epidermis development Inferred from electronic annotation. Source: Compara fatty acid metabolic process Inferred from mutant phenotype PubMed 12600885PubMed 12853447PubMed 16183630. Source: RGD heart development Inferred from expression pattern PubMed 15754086. Source: RGD lipoprotein metabolic process Inferred from mutant phenotype PubMed 15537571. Source: RGD negative regulation of appetite Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of blood pressure Inferred from mutant phenotype PubMed 15967866. Source: RGD negative regulation of cholesterol storage Inferred from electronic annotation. Source: Compara negative regulation of neuron death Inferred from mutant phenotype PubMed 20221904. Source: RGD negative regulation of protein binding Inferred from mutant phenotype PubMed 22198280. Source: RGD negative regulation of receptor biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of sequestering of triglyceride Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription regulatory region DNA binding Inferred from mutant phenotype PubMed 22198280. Source: RGD positive regulation of fatty acid oxidation Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of fatty acid metabolic process Traceable author statement PubMed 12189208. Source: RGD regulation of glycolysis by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from direct assay PubMed 15292030. Source: HGNC response to insulin stimulus Inferred from mutant phenotype PubMed 16183630. Source: RGD wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay PubMed 12189208PubMed 22198280. Source: RGD
Molecular_function	drug binding Inferred from sequence or structural similarity. Source: UniProtKB ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from mutant phenotype PubMed 12189208PubMed 12966092. Source: RGD lipid binding Inferred from sequence or structural similarity. Source: UniProtKB protein complex binding Inferred from mutant phenotype PubMed 20132223. Source: RGD protein domain specific binding Inferred from direct assay PubMed 12189208. Source: RGD sequence-specific DNA binding Inferred from electronic annotation. Source: Compara steroid hormone receptor activity Traceable author statement PubMed 12189208. Source: RGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 468	468	Peroxisome proliferator-activated receptor alpha		PRO_0000053484
Regions
	DNA binding	99 – 173	75	Nuclear receptor
	Zinc finger	102 – 122	21	NR C4-type
	Zinc finger	139 – 161	23	NR C4-type
	Region	280 – 468	189	Ligand-binding By similarity
	Region	304 – 433	130	Required for heterodimerization with RXRA By similarity
Sites
	Site	433	1	Essential for heterodimerization with RXRA By similarity

Sequences

	Sequence		Length	Mass (Da)
	P37230 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: 2A89E7D715C8DBA9	FASTA	468	52,377
	10 20 30 40 50 60 MVDTESPICP LSPLEADDLE SPLSEEFLQE MGNIQEISQS LGEESSGSFS FADYQYLGSC 70 80 90 100 110 120 PGSEGSVITD TLSPASSPSS VSCPAVPTST DESPGNALNI ECRICGDKAS GYHYGVHACE 130 140 150 160 170 180 GCKGFFRRTI RLKLAYDKCD RSCKIQKKNR NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE 190 200 210 220 230 240 KAKLKAEILT CEHDLKDSET ADLKSLAKRI HEAYLKNFNM NKVKARVILA GKTSNNPPFV 250 260 270 280 290 300 IHDMETLCMA EKTLVAKMVA NGVENKEAEV RFFHCCQCMS VETVTELTEF AKAIPGFANL 310 320 330 340 350 360 DLNDQVTLLK YGVYEAIFTM LSSLMNKDGM LIAYGNGFIT REFLKNLRKP FCDIMEPKFD 370 380 390 400 410 420 FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNIGYIEKL QEGIVHVLKL HLQSNHPDDT 430 440 450 460 FLFPKLLQKM VDLRQLVTEH AQLVQVIKKT ESDAALHPLL QEIYRDMY

References

[1]	"Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor." Goettlicher M., Widmark E., Li Q., Gustafsson J.-A. Proc. Natl. Acad. Sci. U.S.A. 89:4653-4657(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin." Shalev A., Siegrist-Kaiser C.A., Yen P.M., Wahli W., Burger A.G., Chin W.W., Meier C.A. Endocrinology 137:4499-4502(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[3]	"Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator." Tien E.S., Davis J.W., Vanden Heuvel J.P. J. Biol. Chem. 279:24053-24063(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CITED2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M88592 mRNA. Translation: AAA41918.1.
IPI	IPI00204351.
PIR	A45288.
RefSeq	NP_037328.1. NM_013196.1.
UniGene	Rn.9753.
3D structure databases
ProteinModelPortal	P37230.
SMR	P37230. Positions 100-179, 200-468.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29529N.
STRING	10116.ENSRNOP00000038651.
PTM databases
PhosphoSite	P37230.
Proteomic databases
PRIDE	P37230.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000030082; ENSRNOP00000038651; ENSRNOG00000021463.
GeneID	25747.
KEGG	rno:25747.
Organism-specific databases
CTD	5465.
RGD	3369. Ppara.
Phylogenomic databases
eggNOG	NOG266867.
GeneTree	ENSGT00700000104361.
HOGENOM	HOG000261626.
HOVERGEN	HBG106004.
InParanoid	P37230.
KO	K07294.
OMA	ICPLSPL.
OrthoDB	EOG4FFD1Q.
Gene expression databases
Genevestigator	P37230.
GermOnline	ENSRNOG00000021463. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.565.10. 2 hits. 3.30.50.10. 1 hit.
InterPro	IPR003074. 1Cnucl_rcpt. IPR003076. 1Cnucl_rcpt_A. IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. IPR001723. Str_hrmn_rcpt. IPR001628. Znf_hrmn_rcpt. IPR013088. Znf_NHR/GATA. [Graphical view]
Pfam	PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR01288. PROXISOMEPAR. PR01289. PROXISOMPAAR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
SUPFAM	SSF48508. Str_ncl_receptor. 1 hit.
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P37230.
ChEMBL	CHEMBL2129.
NextBio	607925.

Entry information

Entry name

PPARA_RAT

Accession

Primary (citable) accession number: P37230

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	April 3, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program