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P23204

- PPARA_MOUSE

UniProt

P23204 - PPARA_MOUSE

Protein

Peroxisome proliferator-activated receptor alpha

Gene

Ppara

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 2 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    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 PER2.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei433 – 4331Essential for heterodimerization with RXRABy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi99 – 17375Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri102 – 12221NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri139 – 16123NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. drug binding Source: UniProtKB
    3. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: Ensembl
    4. lipid binding Source: UniProtKB
    5. protein binding Source: UniProtKB
    6. protein heterodimerization activity Source: UniProtKB
    7. receptor activity Source: MGI
    8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: MGI
    9. sequence-specific DNA binding Source: UniProtKB
    10. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    11. steroid hormone receptor activity Source: MGI
    12. zinc ion binding Source: InterPro

    GO - Biological processi

    1. behavioral response to nicotine Source: Ensembl
    2. circadian regulation of gene expression Source: UniProtKB
    3. enamel mineralization Source: MGI
    4. epidermis development Source: MGI
    5. fatty acid metabolic process Source: MGI
    6. glucose metabolic process Source: MGI
    7. heart development Source: Ensembl
    8. lipid metabolic process Source: MGI
    9. lipoprotein metabolic process Source: Ensembl
    10. negative regulation of appetite Source: UniProtKB
    11. negative regulation of blood pressure Source: Ensembl
    12. negative regulation of cholesterol storage Source: Ensembl
    13. negative regulation of neuron death Source: Ensembl
    14. negative regulation of protein binding Source: Ensembl
    15. negative regulation of receptor biosynthetic process Source: Ensembl
    16. negative regulation of sequestering of triglyceride Source: Ensembl
    17. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    18. negative regulation of transcription regulatory region DNA binding Source: Ensembl
    19. positive regulation of fatty acid oxidation Source: BHF-UCL
    20. positive regulation of gluconeogenesis Source: MGI
    21. positive regulation of transcription, DNA-templated Source: UniProtKB
    22. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    23. regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    24. regulation of circadian rhythm Source: UniProtKB
    25. regulation of fatty acid metabolic process Source: MGI
    26. regulation of gene expression Source: MGI
    27. regulation of glycolytic by positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    28. regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    29. regulation of transcription, DNA-templated Source: MGI
    30. response to hypoxia Source: Ensembl
    31. response to insulin Source: Ensembl
    32. wound healing Source: MGI

    Keywords - Molecular functioni

    Activator, Receptor

    Keywords - Biological processi

    Biological rhythms, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Lipid-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_115781. Bmal1:Clock,Npas2 activates circadian gene expression.
    REACT_118837. Rora activates circadian gene expression.
    REACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
    REACT_198351. RORA activates circadian gene expression.
    REACT_198352. REV-ERBA represses gene expression.
    REACT_198602. PPARA activates gene expression.
    REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
    REACT_198969. Activation of gene expression by SREBF (SREBP).
    REACT_205251. Transcriptional activation of mitochondrial biogenesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Peroxisome proliferator-activated receptor alpha
    Short name:
    PPAR-alpha
    Alternative name(s):
    Nuclear receptor subfamily 1 group C member 1
    Gene namesi
    Name:Ppara
    Synonyms:Nr1c1, Ppar
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:104740. Ppara.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleoplasm Source: Reactome
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Peroxisome proliferators are a diverse group of chemicals that include hypolipidaemic drugs, herbicides and industrial plasticisers. Administration of these chemicals to rodents results in the dramatic proliferation of hepatic peroxisomes as well as liver hyperplasia.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi119 – 1191C → A: Reduces DNA binding and strongly decreases transcriptional activation; when associated with A-122. 1 Publication
    Mutagenesisi122 – 1221C → A: Reduces DNA binding and strongly decreases transcriptional activation; when associated with A-119. 1 Publication
    Mutagenesisi292 – 2921K → A: No effect on interaction with PER2. 1 Publication
    Mutagenesisi459 – 46810Missing: Slightly reduces interaction with PER2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 468468Peroxisome proliferator-activated receptor alphaPRO_0000053482Add
    BLAST

    Proteomic databases

    PRIDEiP23204.

    PTM databases

    PhosphoSiteiP23204.

    Expressioni

    Tissue specificityi

    Highly expressed in liver, kidney and heart. Very weakly expressed in brain and testis.

    Developmental stagei

    It appears first at 13.5 dpc and increases until birth.

    Gene expression databases

    BgeeiP23204.
    CleanExiMM_PPARA.
    GenevestigatoriP23204.

    Interactioni

    Subunit structurei

    Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 AND ASXL2. Interacts with PER2.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Men1O885592EBI-5273083,EBI-3990176

    Protein-protein interaction databases

    BioGridi202317. 15 interactions.
    DIPiDIP-5958N.
    IntActiP23204. 3 interactions.
    STRINGi10090.ENSMUSP00000059719.

    Structurei

    3D structure databases

    ProteinModelPortaliP23204.
    SMRiP23204. Positions 93-468.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni280 – 468189Ligand-bindingBy similarityAdd
    BLAST
    Regioni304 – 433130Required for heterodimerization with RXRABy similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri102 – 12221NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri139 – 16123NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG266867.
    HOGENOMiHOG000261626.
    HOVERGENiHBG106004.
    InParanoidiP23204.
    KOiK07294.
    OMAiTESPICP.
    OrthoDBiEOG7X9G7F.
    PhylomeDBiP23204.
    TreeFamiTF316304.

    Family and domain databases

    Gene3Di1.10.565.10. 2 hits.
    3.30.50.10. 1 hit.
    InterProiIPR003074. 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]
    PfamiPF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view]
    PRINTSiPR01288. PROXISOMEPAR.
    PR01289. PROXISOMPAAR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTiSM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view]
    SUPFAMiSSF48508. SSF48508. 1 hit.
    PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P23204-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVDTESPICP LSPLEADDLE SPLSEEFLQE MGNIQEISQS IGEESSGSFG    50
    FADYQYLGSC PGSEGSVITD TLSPASSPSS VSCPVIPAST DESPGSALNI 100
    ECRICGDKAS GYHYGVHACE GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR 150
    NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE KAKLKAEILT CEHDLKDSET 200
    ADLKSLGKRI HEAYLKNFNM NKVKARVILA GKTSNNPPFV IHDMETLCMA 250
    EKTLVAKMVA NGVEDKEAEV RFFHCCQCMS VETVTELTEF AKAIPGFANL 300
    DLNDQVTLLK YGVYEAIFTM LSSLMNKDGM LIAYGNGFIT REFLKNLRKP 350
    FCDIMEPKFD FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNIGYIEKL 400
    QEGIVHVLKL HLQSNHPDDT FLFPKLLQKM VDLRQLVTEH AQLVQVIKKT 450
    ESDAALHPLL QEIYRDMY 468
    Length:468
    Mass (Da):52,347
    Last modified:October 1, 1996 - v2
    Checksum:i2930A5191C610B6B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti75 – 751A → R in CAA40856. (PubMed:2129546)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57638 mRNA. Translation: CAA40856.1.
    X75289
    , X75290, X75291, X75292, X75293, X75294 Genomic DNA. Translation: CAA53042.1.
    BC016892 mRNA. Translation: AAH16892.1.
    X89577 mRNA. Translation: CAA61754.1.
    CCDSiCCDS27721.1.
    PIRiJC2085.
    RefSeqiNP_001106889.1. NM_001113418.1.
    NP_035274.2. NM_011144.6.
    XP_006520682.1. XM_006520619.1.
    XP_006520683.1. XM_006520620.1.
    XP_006520684.1. XM_006520621.1.
    XP_006520685.1. XM_006520622.1.
    XP_006520686.1. XM_006520623.1.
    UniGeneiMm.212789.

    Genome annotation databases

    EnsembliENSMUST00000057979; ENSMUSP00000059719; ENSMUSG00000022383.
    ENSMUST00000109422; ENSMUSP00000105049; ENSMUSG00000022383.
    ENSMUST00000109423; ENSMUSP00000105050; ENSMUSG00000022383.
    GeneIDi19013.
    KEGGimmu:19013.
    UCSCiuc007xdj.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57638 mRNA. Translation: CAA40856.1 .
    X75289
    , X75290 , X75291 , X75292 , X75293 , X75294 Genomic DNA. Translation: CAA53042.1 .
    BC016892 mRNA. Translation: AAH16892.1 .
    X89577 mRNA. Translation: CAA61754.1 .
    CCDSi CCDS27721.1.
    PIRi JC2085.
    RefSeqi NP_001106889.1. NM_001113418.1.
    NP_035274.2. NM_011144.6.
    XP_006520682.1. XM_006520619.1.
    XP_006520683.1. XM_006520620.1.
    XP_006520684.1. XM_006520621.1.
    XP_006520685.1. XM_006520622.1.
    XP_006520686.1. XM_006520623.1.
    UniGenei Mm.212789.

    3D structure databases

    ProteinModelPortali P23204.
    SMRi P23204. Positions 93-468.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202317. 15 interactions.
    DIPi DIP-5958N.
    IntActi P23204. 3 interactions.
    STRINGi 10090.ENSMUSP00000059719.

    Chemistry

    BindingDBi P23204.
    ChEMBLi CHEMBL2128.
    GuidetoPHARMACOLOGYi 593.

    PTM databases

    PhosphoSitei P23204.

    Proteomic databases

    PRIDEi P23204.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000057979 ; ENSMUSP00000059719 ; ENSMUSG00000022383 .
    ENSMUST00000109422 ; ENSMUSP00000105049 ; ENSMUSG00000022383 .
    ENSMUST00000109423 ; ENSMUSP00000105050 ; ENSMUSG00000022383 .
    GeneIDi 19013.
    KEGGi mmu:19013.
    UCSCi uc007xdj.2. mouse.

    Organism-specific databases

    CTDi 5465.
    MGIi MGI:104740. Ppara.

    Phylogenomic databases

    eggNOGi NOG266867.
    HOGENOMi HOG000261626.
    HOVERGENi HBG106004.
    InParanoidi P23204.
    KOi K07294.
    OMAi TESPICP.
    OrthoDBi EOG7X9G7F.
    PhylomeDBi P23204.
    TreeFami TF316304.

    Enzyme and pathway databases

    Reactomei REACT_115781. Bmal1:Clock,Npas2 activates circadian gene expression.
    REACT_118837. Rora activates circadian gene expression.
    REACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
    REACT_198351. RORA activates circadian gene expression.
    REACT_198352. REV-ERBA represses gene expression.
    REACT_198602. PPARA activates gene expression.
    REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
    REACT_198969. Activation of gene expression by SREBF (SREBP).
    REACT_205251. Transcriptional activation of mitochondrial biogenesis.

    Miscellaneous databases

    NextBioi 295428.
    PROi P23204.
    SOURCEi Search...

    Gene expression databases

    Bgeei P23204.
    CleanExi MM_PPARA.
    Genevestigatori P23204.

    Family and domain databases

    Gene3Di 1.10.565.10. 2 hits.
    3.30.50.10. 1 hit.
    InterProi 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 ]
    Pfami PF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PRINTSi PR01288. PROXISOMEPAR.
    PR01289. PROXISOMPAAR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators."
      Issemann I., Green S.
      Nature 347:645-650(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structure of the mouse peroxisome proliferator activated receptor alpha gene."
      Gearing K.L., Crickmore A., Gustafsson J.-A.
      Biochem. Biophys. Res. Commun. 199:255-263(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/Sv.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Kidney.
    4. "Chromosomal localisation, inducibility, tissue-specific expression and strain differences in three murine peroxisome-proliferator-activated-receptor genes."
      Jones P.S., Savory R., Barratt P., Bell A.R., Gray T.J.B., Jenkins N.A., Gilbert D.J., Copeland N.G., Bell D.R.
      Eur. J. Biochem. 233:219-226(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 413-468.
      Strain: Swiss Webster.
      Tissue: Liver.
    5. "Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor."
      Zhu Y., Qi C., Jain S., Rao M.S., Reddy J.K.
      J. Biol. Chem. 272:25500-25506(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPARBP.
    6. "Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action."
      Rubino D., Driggers P., Arbit D., Kemp L., Miller B., Coso O., Pagliai K., Gray K., Gutkind S., Segars J.
      Oncogene 16:2513-2526(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AKAP13.
    7. "Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR."
      Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.
      J. Biol. Chem. 275:13510-13516(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NCOA6.
    8. "Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha."
      Fu J., Gaetani S., Oveisi F., Lo Verme J., Serrano A., Rodriguez De Fonseca F., Rosengarth A., Luecke H., Di Giacomo B., Tarzia G., Piomelli D.
      Nature 425:90-93(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION AS RECEPTOR FOR OLEYLETHANOLAMIDE, FUNCTION.
    9. "Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway."
      Finck B.N., Gropler M.C., Chen Z., Leone T.C., Croce M.A., Harris T.E., Lawrence J.C. Jr., Kelly D.P.
      Cell Metab. 4:199-210(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LIPN1.
    10. Cited for: INTERACTION WITH PRDM16.
    11. "Identification of a physiologically relevant endogenous ligand for PPARalpha in liver."
      Chakravarthy M.V., Lodhi I.J., Yin L., Malapaka R.R., Xu H.E., Turk J., Semenkovich C.F.
      Cell 138:476-488(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION OF 1-PALMITOYL-2-OLEOYL-SN-GLYCEROL-3-PHOSPHOCHOLINE AS A PHYSIOLOGICAL LIGAND, DNA-BINDING, FUNCTION, MUTAGENESIS OF CYS-119 AND CYS-122.
    12. "The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
      Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
      Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CIRCADIAN RHYTHMS, INTERACTION WITH PER2, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-292 AND 459-LEU--TYR-468.

    Entry informationi

    Entry nameiPPARA_MOUSE
    AccessioniPrimary (citable) accession number: P23204
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1991
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 156 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3