Homo sapiens complex locus PPARD, encoding peroxisome proliferator-activated receptor delta.
SUMMARY back to top
RefSeq summary
[PPARD] This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. PPARs are nuclear hormone receptors that bind peroxisome proliferators and control the size and number of peroxisomes produced by cells. PPARs mediate a variety of biological processes, and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer. This protein is a potent inhibitor of ligand-induced transcription activity of PPAR alpha and PPAR gamma. It may function as an integrator of transcription repression and nuclear receptor signaling. The expression of this gene is found to be elevated in colorectal cancer cells. The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein related to APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation. Alternate splicing results in multiple transcript variants. [provided by RefSeq].

RefSeq annotates 5 representative transcripts (NM included in AceView variants .b, .c, .d, .e and .f), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 27 spliced variants.

AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at high level, 2.8 times the average gene in this release. The sequence of this gene is defined by 317 GenBank accessions from 290 cDNA clones, some from brain (seen 21 times), placenta (18), hippocampus (17), placenta normal (17), cerebellum (15), uterus (13), lung (8) and 87 other tissues. We annotate structural defects or features in 7 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 37 distinct introns (34 gt-ag, 2 gc-ag, 1 other). Transcription produces 30 different mRNAs, 27 alternatively spliced variants and 3 unspliced forms. There are 6 probable alternative promotors, 9 non overlapping alternative last exons and 6 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 19 cassette exons, overlapping exons with different boundaries. 366 bp of this gene are antisense to spliced gene yosiya.bAug10, raising the possibility of regulated alternate expression.
Note that mRNA .qAug10 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD).
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant aAug10).
Function: There are 165 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (Arteriosclerosis; Breast Neoplasms; Cholesterol, HDL/blood*; Chronic Disease; Diabetes mellitus, type 2; Dyslipidemias; Fasting; Hyperplasia; Inflammation and 4 others), proposed to participate in pathways (Acute myeloid leukemia, Basic mechanism of action of PPARa PPARb(d) and PPARg and effects on gene expression, Pathways in cancer, PPAR signaling pathway, Wnt signaling pathway) and processes (adipose tissue development, anagen, axon ensheathment, cell differentiation, cell proliferation, cell-substrate adhesion, fatty acid beta-oxidation, fatty acid transport, keratinocyte migration, keratinocyte proliferation, lipid metabolic process, negative regulation of epithelial cell proliferation, negative regulation of transcription from RNA polymerase II promoter, placenta development, positive regulation of cell proliferation, positive regulation of phosphoinositide 3-kinase cascade, response to glucose stimulus, vitamin A metabolic process, wound healing). Proteins are expected to have molecular functions (DNA binding, fatty acid binding, metal ion binding, NF-kappaB binding, protein binding, sequence-specific DNA binding, steroid hormone receptor activity, transcription repressor activity, zinc ion binding) and to localize in various compartments (cytoplasm, nucleus). Putative protein interactors have been described (BCL6, CEP350, DUT, EP300, GADD45B, GADD45G, HDAC1, HDAC2, HDAC3, HDAC4, HDAC7, NCOR1, NCOR2, NR0B2, NRIP1, PEBP1, PPARD, PRDX6, PROX1, RANBP9, RXRA, RXRB, RXRG, SMAD9, SPEN, SRC).
Protein coding potential: 16 spliced and the unspliced mRNAs putatively encode good proteins, altogether 15 different isoforms (7 complete, 3 COOH complete, 5 partial), some containing domains Ligand-binding domain of nuclear hormone receptor, Zinc finger, C4 type (two domains) [Pfam]. The remaining 13 mRNA variants (11 spliced, 2 unspliced; 1 partial) appear not to encode good proteins.
Isoform PPARD.jAug10-unspliced is annotated using as Met a Kozak-compatible g..CTGg start, thereby gaining 90 amino acids N-terminal to the first AUG. Finally proteins from this gene may be modulated by mono-methylation, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 6, links to other databases and other names
Map: This gene PPARD maps on chromosome 6, at 6p21.2 according to Entrez Gene. In AceView, it covers 86.39 kb, from 35309580 to 35395970 (NCBI 37, August 2010), on the direct strand.
Links to: , manual annotations from GAD, KEGG_03320, KEGG_04310, KEGG_05200, KEGG_05221, PhosphoSite, the SNP view, gene overviews from Entrez Gene 5467, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as PPARD, FAAR, NUC1, NUCI, NR1C2, NUCII, PPARB or MGC3931, LOC5467. It has been described as peroxisome proliferator-activated receptor delta, PPAR-beta, PPAR-delta, OTTHUMP00000016256, OTTHUMP00000016257, nuclear hormone receptor 1, nuclear receptor subfamily 1 group C member 2, peroxisome proliferator-activated receptor beta.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene Ppardand1810013A23Rik (e=2 10-06).
The closest C.elegans gene, according to BlastP, is the AceView/WormGene nhr-85 (e=4 10-27), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 3811 bp 441 aa 416 bp 2069 bp 42 bp 2kb probably including promoter 85540 bp 1kb
bAug10 4132 bp 441 aa 692 bp 2114 bp 2kb possibly including promoter 86019 bp 1kb
cAug10 3845 bp 441 aa 405 bp 2114 bp 2kb probably including promoter 85636 bp 1kb
dAug10 3518 bp 402 aa 195 bp 2114 bp 2kb probably including promoter 85636 bp 1kb
eAug10 2006 bp 361 aa 309 bp 611 bp 2kb probably including promoter 82841 bp 1kb
fAug10 3455 bp 343 aa 309 bp 2114 bp 2kb including Promoter 85636 bp 1kb
gAug10 688 bp 151 aa 234 bp 2kb possibly including promoter 75105 bp 1kb
hAug10 615 bp 133 aa 214 bp 2kb including Promoter 79367 bp 1kb
iAug10 571 bp 132 aa 175 bp 2kb possibly including promoter 2738 bp 1kb
jAug10-unspliced 600 bp 129 aa 213 bp 2kb possibly including promoter 600 bp 1kb
kAug10 568 bp 117 aa 197 bp 17 bp 2kb possibly including promoter 80062 bp 1kb
lAug10 619 bp 113 aa 278 bp 66 bp 2kb including Promoter 79259 bp 1kb
mAug10 566 bp 105 aa 230 bp 18 bp 66 bp 2kb including Promoter 77607 bp 1kb
nAug10 643 bp 94 aa 356 bp 2kb 7868 bp 1kb
oAug10 804 bp 74 aa 31 bp 548 bp 2kb probably including promoter 14339 bp 1kb
pAug10 650 bp 69 aa 439 bp 2kb 1818 bp 1kb
qAug10 612 bp 57 aa 438 bp 42 bp 2kb probably including promoter 81561 bp 1kb
rAug10 1236 bp 65 aa 16 bp 1022 bp 2kb including Promoter 76917 bp 1kb
sAug10 1169 bp 67 aa 208 bp 757 bp 2kb probably including promoter 14225 bp 1kb
tAug10-unspliced 917 bp 88 aa 102 bp 548 bp 2kb 917 bp 1kb
uAug10-unspliced 876 bp 81 aa 87 bp 543 bp 2kb 876 bp 1kb
vaAug10 783 bp 41 aa 657 bp 2kb 1884 bp 1kb
vbAug10 586 bp 33 aa 156 bp 328 bp 2kb including Promoter 6183 bp 1kb
vcAug10 557 bp 35 aa 153 bp 296 bp 2kb including Promoter 77597 bp 1kb
vdAug10 555 bp 47 aa 184 bp 227 bp 2kb including Promoter 13896 bp 1kb
veAug10 553 bp 53 aa 153 bp 238 bp 2kb including Promoter 68604 bp 1kb
vfAug10 550 bp 44 aa 185 bp 230 bp 2kb including Promoter 68428 bp 1kb
vgAug10 549 bp 43 aa 226 bp 191 bp 2kb including Promoter 13942 bp 1kb
vhAug10 495 bp 44 aa 156 bp 204 bp 2kb including Promoter 41306 bp 1kb
viAug10 453 bp 54 aa 126 bp 162 bp 2kb including Promoter 68508 bp 1kb

Gene neighbors and Navigator on chromosome 6p21.2 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               165 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e, .f, .g, .h, .i, .j-u, .k, .l, .m, .n, .o, .p, .q, .r, .s, .t-u, .u-u, .va, .vb, .vc, .vd, .ve, .vf, .vg, .vh, .vi Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DCI

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

If you know more about this gene, or found errors, please share your knowledge. Thank you !