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PTCH2 (patched homolog 2 (Drosophila))

Identity

Other namesPTC2
Patched 2
Patched homolog 2
HGNC (Hugo) PTCH2
LocusID (NCBI) 8643
Location 1p34.1
Location_base_pair Starts at 45285516 and ends at 45308616 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Tel-PLK3-LOC343521-LOC149478-PTCH2-EIF2B3-LOC728887- LOC128192-Cen

DNA/RNA

Description 23 exons, approximately 20 kb of genomic sequence. The last exon is exon 22 due to the presence of exons 12A and 12B.
Transcription Altrenative splice variants, skipping of exons 9 and 10 - maintenance of reading frame, skipping of exon 9 - maintenance of reading frame, skipping of exon 21- change of reading frame. Alternative 3' end - termination within intron 21.

Protein

Description Putative 12 transmembrane protein, similar to PTCH1. Receptor of Hedgehog ligands but can not transduce signal activity as PTCH1 does.
Expression Mainly testis and skin, generally weaker than PTCH1, gene expression dependent on Hedgehog signaling activation, as in PTCH1. However, in PTCH1 the up-regulation of gene expression due to signaling activation results in a negative feedback loop due to inhibition of the activity of the transmenbrane protein, Smoothened, but this does not appear to be the case for PTCH2.
Localisation Cellular membranes.
Function Receptor of Hedgehog ligands but lacks the strong capacity of PTCH1 to inhibit the signaling molecule Smoothened, which, through a series of intracellular events, activates the GLI family of transcription factors. Thus, while PTCH1 regulates Smoothened activity depending on Hedgehog ligand binding, PTCH2 is not. This is despite the fact that the three mammalian Hedgehog ligands Sonic, Desert and Indian Hedgehog have similar affinity for both PTCH1 and PTCH2. The expression of the PTCH2 receptor and the Desert Hedgehog ligand in the testis, as well as the requirement of Desert Hedgehog in testicular development has led to the proposal that PTCH2 may mediate the Desert Hedgehog effects in that tissue and could act as a tumor suppressor in germ cell tumors, as these are frequently deleted in 1p33-34. However, no PTCH2 mutations have been identified in such tumors and knock-out mouse models of PTCH2 have not revealed any testicular phenotype.
Homology Homolog to PTCH1. Mouse, Chicken and Zebrafish have both PTCH homologs but Drosophila only one.

Mutations

Germinal None described
Somatic Only two cases reported :
  • Medulloblastomas, 2bp deletion in exon 8 - germline DNA not checked.
  • Basal Cell Carcinoma, nucleotide change in intron 20, five bases from 5' splice junction.

    • Implicated in

    Entity Various cancers
    Note There are no genetic diseases or tumors where the role of PTCH2 has been clearly demonstrated by the unambiguous detection of PTCH2 mutations that disrupt the protein function.
    The various suggestions of a possible role of PTCH2 in tumor development are generally circumstantial and are mostly based on chromosomal deletions that encompass the PTCH2 genomic region. The strongest evidence that PTCH2 hay have a role in tumor development comes from knock-out mouse model systems. Thus while Ptch2(-/-) mice have no obvious phenotype and do not develop tumors, if they are crossed with Ptch1 (+/-) heterozygotes, then the resulting Ptch2(-/-)Ptch1(+/-) mice developed at a higher incidence typical Ptch1(+/-) tumors such as medulloblastomas and rhabdomyosarcomas, suggesting genetic interactions between Ptch2 and Ptch1.
    A possible role of PTCH2 in testicular development, acting as a Desert Hedgehog receptor has been suggested.
    Overexpression of PTCH2 in basal cell carcinomas cannot compensate for mutated PTCH1 implying distinct roles of the two homologs. This can be rationalized by the very weak capacity of PTCH2 relative to PTCH1 in inhibiting the signaling molecule Smoothened. Additionally, based mostly on chromosomal deletion in the 1p32-34 region where the PTCH2 gene resides, a role in neurofibromas, pituitary tumors, medulloblastomas and meningiomas has been proposed. Also, PTCH2 is implicated in thymus, dental, prostate, ovary, and bone tissue development, as PTCH2 expression has been detected in these tissues.
    In a mouse model, deletions of exons 5 to 17 in both Ptch2 alleles did not result in any obvious phenotype. However in the context of Ptch1+/- mice, this deletion of Ptch2 resulted in higher incidence and broader spectrum of tumor formation. In another mouse model of Ptch2, with a targeted insertion in exon 6 that would results in premature termination, the resulting homozygous mice were characterized with alopecia and epidermal hyperplasia.
      

    External links

    Nomenclature
    HGNC (Hugo)PTCH2   9586
    Entrez_Gene (NCBI)PTCH2  8643  patched 2
    Cards
    AtlasPTCH2ID41892ch1p34
    GeneCards (Weizmann)PTCH2
    Ensembl (Hinxton)ENSG00000117425 [Gene_View]  chr1:45285516-45308616 [Contig_View]  PTCH2 [Vega]
    AceView (NCBI)PTCH2
    Genatlas (Paris)PTCH2
    euGene (Indiana)8643
    SOURCE (Stanford)NM_001166292 NM_003738
    Genomic and cartography
    GoldenPath (UCSC)PTCH2  -  1p34.1   chr1:45285516-45308616 -  1p34.1   [Description]    (hg19-Feb_2009)
    EnsemblPTCH2 - 1p34.1 [CytoView]
    Mapping of homologs : NCBIPTCH2 [Mapview]
    OMIM155255   603673   605462   613545   
    Gene and transcription
    Genbank (Entrez)AA781365 AF087651 AF091501 AF119569 AI798853
    RefSeq transcript (SRS)NM_001166292 NM_003738
    RefSeq transcript (Entrez)NM_001166292 NM_003738
    RefSeq genomic (SRS)AC_000133 NC_000001 NG_013369 NT_032977 NW_001838578
    RefSeq genomic (Entrez)AC_000133 NC_000001 NG_013369 NT_032977 NW_001838578
    Consensus coding sequences : CCDS (NCBI)PTCH2
    Cluster EST : UnigeneHs.591497 [ SRS ] Hs.591497 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)15523
    Alternative Splicing GalleryENSG00000117425
    Gene ExpressionPTCH2 [ NCBI-GEO ]   PTCH2 [ EBI - ARRAY_EXPRESS ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9Y6C5 (SRS) Q9Y6C5 (Uniprot)
    With graphics : InterProQ9Y6C5
    Splice isoforms : SwissVarQ9Y6C5(Swissvar)
    Domaine pattern : Prosite (SRS)SSD (PS50156)   
    Domaine pattern : Prosite (Expaxy)SSD (PS50156)   
    Domains : Interpro (SRS)Patched    SSD    TM_rcpt_patched   
    Domains : Interpro (EBI)Patched    SSD    TM_rcpt_patched   
    Related proteins : CluSTrQ9Y6C5
    Domain families : Pfam (SRS)Patched (PF02460)   
    Domain families : Pfam (Sanger)Patched (PF02460)   
    Domain families : Pfam (NCBI)pfam02460   
    Blocks (Seattle)Q9Y6C5
    Human Protein AtlasENSG00000117425
    HPRD04722
    IPIIPI00419647   IPI00471943   IPI00844378   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9Y6C5
    IntAct (EBI)Q9Y6C5
    FunCoupENSG00000117425
    REACTOMEPTCH2
    BioGRIDPTCH2
    InParanoidQ9Y6C5
    Interologous Interaction database Q9Y6C5
    Polymorphism : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)PTCH2
    SNP (GeneSNP Utah)PTCH2
    SNP : HGBasePTCH2
    Genetic variants : HAPMAPPTCH2
    Somatic Mutations in Cancer : COSMICPTCH2 
    CONAN: Copy Number AnalysisPTCH2 
    Mutations and Diseases : HGMDPTCH2
    OMIM155255    603673    605462    613545   
    GENETests155255    603673    605462    613545   
    Disease Genetic AssociationPTCH2
    Huge Navigator PTCH2 [HugePedia]  PTCH2 [HugeCancerGEM]
    Genomic VariantsPTCH2
    snp3D : Map Gene to Disease8643
    General knowledge
    Homologs : HomoloGenePTCH2
    Homology/Alignments : Family Browser (UCSC)PTCH2
    Phylogenetic Trees/Animal Genes : TreeFamPTCH2
    Chemical/Protein Interactions : CTD8643
    Chemical/Pharm GKB GenePA33938
    Clinical trialPTCH2
    Cancer Resource (Charite)ENSG00000117425
    Ontology : AmiGOreceptor activity  smoothened binding  hedgehog receptor activity  membrane  integral to membrane  hair cycle  skin development  negative regulation of smoothened signaling pathway  hedgehog family protein binding  hedgehog family protein binding  
    Ontology : EGO-EBIreceptor activity  smoothened binding  hedgehog receptor activity  membrane  integral to membrane  hair cycle  skin development  negative regulation of smoothened signaling pathway  hedgehog family protein binding  hedgehog family protein binding  
    Pathways : KEGGHedgehog signaling pathway
    Other databases
    Probes
    Probes : ImagenesPTCH2 Related clones (RZPD - Berlin)
    Litterature
    PubMed13 Pubmed reference(s) in Entrez
    PubGenePTCH2
    iHOPPTCH2

    Bibliography

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    Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice.
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    The British journal of dermatology. 2003 ; 148 (2) : 337-341.
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    A molecular fingerprint for medulloblastoma.
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    Expression of hedgehog proteins in the human thymus.
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    PMID 14566027
     
    Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells.
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    The Journal of biological chemistry. 2003 ; 278 (20) : 18506-18513.
    PMID 12626524
     
    Molecular profiling of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1, based on large-scale real-time RT-PCR.
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    Molecular cancer. 2004 ; 3 : page 20.
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    Distinct roles of PTCH2 splice variants in Hedgehog signalling.
    Rahnama F, Toftgˆ€rd R, Zaphiropoulos PG
    The Biochemical journal. 2004 ; 378 (Pt 2) : 325-334.
    PMID 14613484
     
    Genomic annotation of the meningioma tumor suppressor locus on chromosome 1p34.
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    Oncogene. 2004 ; 23 (4) : 1014-1020.
    PMID 14749765
     
    Molecular abnormalities in pediatric embryonal brain tumors--analysis of loss of heterozygosity on chromosomes 1, 5, 9, 10, 11, 16, 17 and 22.
    Zakrzewska M, Rieske P, Debiec-Rychter M, Zakrzewski K, Polis L, Fiks T, Liberski PP
    Clinical neuropathology. 2004 ; 23 (5) : 209-217.
    PMID 15581023
     
    The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway.
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    PLoS genetics. 2005 ; 1 (2) : page e19.
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    Expression patterns of hedgehog signaling peptides in naturally acquired equine osteochondrosis.
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    Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2005 ; 23 (5) : 1152-1159.
    PMID 16140195
     
    Expression and function of sonic hedgehog pathway components in pituitary adenomas: evidence for a direct role in hormone secretion and cell proliferation.
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    Desert hedgehog-patched 2 expression in peripheral nerves during Wallerian degeneration and regeneration.
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    Journal of neurobiology. 2006 ; 66 (3) : 243-255.
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    Cancer research. 2006 ; 66 (14) : 6964-6971.
    PMID 16849540
     
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    Journal of dental research. 2006 ; 85 (5) : 427-431.
    PMID 16632755
     
    Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia.
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    Molecular and cellular biology. 2006 ; 26 (17) : 6609-6622.
    PMID 16914743
     
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    Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand.
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    PMID 17392501
     
    Sonic and desert hedgehog signaling in human fetal prostate development.
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    PMID 17342747
     
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    Contributor(s)

    Written02-2008Peter Zaphiropoulos
    Department of Biosciences and Nutrition, Karolinska Institute, 14157 Huddinge, Sweden

    Citation

    This paper should be referenced as such :
    Zaphiropoulos P . PTCH2 (patched homolog 2 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. February 2008 .
    URL : http://AtlasGeneticsOncology.org/Genes/PTCH2ID41892ch1p34.html

    This paper is referenced by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/38598/1/02-2008-PTCH2ID41892ch1p34.pdf   [ Bibliographic record ]

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