RefSeq annotates one representative transcript (NM included in AceView variant.a), but Mus musculus 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 9 spliced variants.
AceView synopsis, each blue text links to tables and details Expression: According to AceView, this gene is expressed at high level, 2.6 times the average gene in this release. The sequence of this gene is defined by 282 GenBank accessions from 240 cDNA clones, some from brain (seen 35 times), whole brain (25), upper head (15), embryonic stem cell (13), taste buds (10), tongue (10), eye (9) and 60 other tissues. We annotate structural defects or features in 4 cDNA clones. Alternative mRNA variants and regulation: The gene contains 30 distinct introns (29 gt-ag, 1 gc-ag). Transcription produces 13 different mRNAs, 9 alternatively spliced variants and 4 unspliced forms. There are 7 probable alternative promotors, 3 non overlapping alternative last exons and 3 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 a cassette exon, overlapping exons with different boundaries, splicing versus retention of 2 introns.
Note that mRNA .bSep07 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD). Function: There are 373 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (cardiovascular system phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; embryogenesis phenotype; endocrine/exocrine gland phenotype; growth/size phenotype; lethality-embryonic/perinatal; life span-post-weaning/aging and 8 others), proposed to participate in pathways (Basal cell carcinoma, Hedgehog signaling pathway) and processes (dorsal/ventral pattern formation, embryonic limb morphogenesis, mammary gland development, negative regulation of body size, neural tube formation, organ morphogenesis, protein processing, regulation of smoothened activity, signal transduction, smoothened signaling pathway). Proteins are expected to have molecular functions (cholesterol binding, hedgehog receptor activity, heparin binding, patched binding, protein binding, zinc ion binding) and to localize in various compartments (extracellular region, integral to membrane, integral to plasma membrane).
Please see the Jackson Laboratory Mouse Genome Database/Informatics site MGI_105373 for in depth functional annotation of this gene. Protein coding potential: 7 spliced and 3 unspliced mRNAs putatively encode good proteins, altogether 11 different isoforms (3 complete, 4 COOH complete, 4 partial), some containing patched domain [Pfam], some transmembrane domains [Psort2]. The remaining 3 mRNA variants (2 spliced, 1 unspliced; 2 partial) appear not to encode good proteins.
2 isoforms are annotated using as Met a Kozak-compatible non-AUG start, thereby gaining a minimum of 84 amino acids N-terminal to the first AUG.
Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12. Map on chromosome 13, links to other databases and other names Map: This gene Ptch1 maps on chromosome 13, at 13 B3|13 36.0 cM according to Entrez Gene. In AceView, it covers 65.32 kb, from 63674768 to 63609453 (NCBI 37a, Aug 2007), on the reverse strand. Links to: manual annotations from MGI_105373, KEGG_04340, KEGG_05217, the SNP view, gene overviews from Entrez Gene 19206, expression data from UniGene, molecular and other annotations from UCSC. Other names: The gene is also known as Ptch1, Ptc, mes, Ptc1, PTCH or A230106A15Rik, LOC19206. Closest AceView homologs in other species ? The closest human gene, according to BlastP, is the AceView gene PTCH1 (e=9 10-18). The closest C.elegans genes, according to BlastP, are the AceView/WormGenes ptc-3 (e=8 10-06), ptc-1 (e=10-04), which may contain interesting functional annotation. The closest A.thaliana gene, according to BlastP, is the AceView gene AT4G38350 (e=4 10-29), which may contain interesting functional annotation
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. Read more...
Mouse over the ending of each transcript gives tissues from which the supporting cDNAs were extracted. Details on tissue of origin for each intron and exon is available from the intron and exons table.
Click on any transcript to open the specific mRNA page, to see the exact cDNA clone support and eventual SNPs and to get details on tissues, sequences, mRNA and protein annotations. Proteins supported by a single continuous cDNA sequence lead to underlining the name/ending of the variant. Names not underlined result from cDNA concatenation in the coding region and should be experimentally checked.
Introns are depicted by broken lines; the height of the top of each intron reflects the relative number of clones supporting this intron. ]^[ A pink broken line denotes an intron with standard boundaries (gt-ag or gc-ag) that is exactly supported (i.e. a cDNA sequence exactly matches the genome over 16 bp, 8 on both sides of the intron). ] ^ ] A blue broken line denotes non-standard introns, exactly supported, but with non-standard at-ac or any other boundaries. ]-[ Pink and ] - ] blue straight lines represent 'fuzzy' introns of the standard and non-standard types respectively, those introns do not follow the 16 bp rule. Black straight lines ]-[denote gaps in the alignments.
Exons: Wide filled pink areas represent putative protein coding regions, narrow empty pink boxes represent the 5'UTR (on the left) and 3' UTR (on the right). Flags identify validated endings: cap site on the 5' side, polyadenylation site on the 3' side. Filled flags correspond to frequent events while empty flags have lesser supporting cDNAs (yet all are validated); at the 3' side, black flags are associated to the main AATAAA signal, blue flags to any single letter variant of the main . More explanations are given in the gene help file
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'.
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