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PTCH2 (patched homolog 2 (Drosophila))

Written2008-02Peter Zaphiropoulos
Department of Biosciences, Nutrition, Karolinska Institute, 14157 Huddinge, Sweden

(Note : for Links provided by Atlas : click)

Identity

Alias_namespatched (Drosophila) homolog 2
patched homolog 2 (Drosophila)
Other aliasPTC2
Patched 2
Patched homolog 2
HGNC (Hugo) PTCH2
LocusID (NCBI) 8643
Atlas_Id 41892
Location 1p34.1  [Link to chromosome band 1p34]
Location_base_pair Starts at 44819844 and ends at 44842944 bp from pter ( according to hg19-Feb_2009)  [Mapping PTCH2.png]
Local_order Tel-PLK3-LOC343521-LOC149478-PTCH2-EIF2B3-LOC728887- LOC128192-Cen
Fusion genes
(updated 2016)
RET (10q11.21) / PTCH2 (1p34.1)

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

    Note
      
    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.
      

    Bibliography

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    Development of stratum intermedium and its role as a Sonic hedgehog-signaling structure during odontogenesis.
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    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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    Patched2 modulates tumorigenesis in patched1 heterozygous mice.
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    PMID 16849540
     
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    PMID 10075838
     
    Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog.
    Motoyama J, Takabatake T, Takeshima K, Hui C
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    PMID 9462734
     
    Sonic hedgehog signaling is important in tooth root development.
    Nakatomi M, Morita I, Eto K, Ota MS
    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.
    Nieuwenhuis E, Motoyama J, Barnfield PC, Yoshikawa Y, Zhang X, Mo R, Crackower MA, Hui CC
    Molecular and cellular biology. 2006 ; 26 (17) : 6609-6622.
    PMID 16914743
     
    Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling activity during chick embryogenesis.
    Pearse RV 2nd, Vogan KJ, Tabin CJ
    Developmental biology. 2001 ; 239 (1) : 15-29.
    PMID 11784016
     
    Distinct roles of PTCH2 splice variants in Hedgehog signalling.
    Rahnama F, Toftgå R, Zaphiropoulos PG
    The Biochemical journal. 2004 ; 378 (Pt 2) : 325-334.
    PMID 14613484
     
    Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand.
    Rossi P, Lolicato F, Grimaldi P, Dolci S, Di Sauro A, Filipponi D, Geremia R
    Gene expression patterns : GEP. 2008 ; 8 (2) : 58-70.
    PMID 18036996
     
    The hedgehog signaling pathway in the mouse ovary.
    Russell MC, Cowan RG, Harman RM, Walker AL, Quirk SM
    Biology of reproduction. 2007 ; 77 (2) : 226-236.
    PMID 17392501
     
    Expression of hedgehog proteins in the human thymus.
    Sacedón R, Varas A, Hern´ndez-Ló C, Gutiérrez-deFrí C, Crompton T, Zapata AG, Vicente A
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2003 ; 51 (11) : 1557-1566.
    PMID 14566027
     
    Expression patterns of hedgehog signaling peptides in naturally acquired equine osteochondrosis.
    Semevolos SA, Strassheim ML, Haupt JL, Nixon AJ
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2005 ; 23 (5) : 1152-1159.
    PMID 16140195
     
    Lack of Rb and p53 delays cerebellar development and predisposes to large cell anaplastic medulloblastoma through amplification of N-Myc and Ptch2.
    Shakhova O, Leung C, van Montfort E, Berns A, Marino S
    Cancer research. 2006 ; 66 (10) : 5190-5200.
    PMID 16707443
     
    Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32.
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    PMID 9931336
     
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    Sulman EP, White PS, Brodeur GM
    Oncogene. 2004 ; 23 (4) : 1014-1020.
    PMID 14749765
     
    Expression of hedgehog signalling components in adult mouse testis.
    Szczepny A, Hime GR, Loveland KL
    Developmental dynamics : an official publication of the American Association of Anatomists. 2006 ; 235 (11) : 3063-3070.
    PMID 16958114
     
    Expression and function of sonic hedgehog pathway components in pituitary adenomas: evidence for a direct role in hormone secretion and cell proliferation.
    Vila G, Theodoropoulou M, Stalla J, Tonn JC, Losa M, Renner U, Stalla GK, Paez-Pereda M
    The Journal of clinical endocrinology and metabolism. 2005 ; 90 (12) : 6687-6694.
    PMID 16159933
     
    Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells.
    Wang BE, Shou J, Ross S, Koeppen H, De Sauvage FJ, Gao WQ
    The Journal of biological chemistry. 2003 ; 278 (20) : 18506-18513.
    PMID 12626524
     
    Hedgehog signaling in mouse ovary: Indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells.
    Wijgerde M, Ooms M, Hoogerbrugge JW, Grootegoed JA
    Endocrinology. 2005 ; 146 (8) : 3558-3566.
    PMID 15878962
     
    Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice.
    Yamago G, Takata Y, Furuta I, Urase K, Momoi T, Huh N
    Archives of dermatological research. 2001 ; 293 (9) : 435-441.
    PMID 11758785
     
    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
     
    PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas.
    Zaphiropoulos PG, Undén AB, Rahnama F, Hollingsworth RE, Toftgård R
    Cancer research. 1999 ; 59 (4) : 787-792.
    PMID 10029063
     
    Sonic and desert hedgehog signaling in human fetal prostate development.
    Zhu G, Zhau HE, He H, Zhang L, Shehata B, Wang X, Cerwinka WH, Elmore J, He D
    The Prostate. 2007 ; 67 (6) : 674-684.
    PMID 17342747
     

    Citation

    This paper should be referenced as such :
    Zaphiropoulos, P
    PTCH2 (patched homolog 2 (Drosophila))
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):435-437.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/PTCH2ID41892ch1p34.html


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
      Familial nervous system tumour syndromes Naevoid basal cell carcinoma syndrome (NBCS)


    External links

    Nomenclature
    HGNC (Hugo)PTCH2   9586
    Cards
    AtlasPTCH2ID41892ch1p34
    Entrez_Gene (NCBI)PTCH2  8643  patched 2
    AliasesPTC2
    GeneCards (Weizmann)PTCH2
    Ensembl hg19 (Hinxton)ENSG00000117425 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000117425 [Gene_View]  chr1:44819844-44842944 [Contig_View]  PTCH2 [Vega]
    ICGC DataPortalENSG00000117425
    TCGA cBioPortalPTCH2
    AceView (NCBI)PTCH2
    Genatlas (Paris)PTCH2
    WikiGenes8643
    SOURCE (Princeton)PTCH2
    Genetics Home Reference (NIH)PTCH2
    Genomic and cartography
    GoldenPath hg38 (UCSC)PTCH2  -     chr1:44819844-44842944 -  1p34.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)PTCH2  -     1p34.1   [Description]    (hg19-Feb_2009)
    EnsemblPTCH2 - 1p34.1 [CytoView hg19]  PTCH2 - 1p34.1 [CytoView hg38]
    Mapping of homologs : NCBIPTCH2 [Mapview hg19]  PTCH2 [Mapview hg38]
    OMIM109400   155255   603673   605462   
    Gene and transcription
    Genbank (Entrez)AA781365 AF087651 AF091501 AF119569 AI798853
    RefSeq transcript (Entrez)NM_001166292 NM_003738
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)PTCH2
    Cluster EST : UnigeneHs.591497 [ NCBI ]
    CGAP (NCI)Hs.591497
    Alternative Splicing GalleryENSG00000117425
    Gene ExpressionPTCH2 [ NCBI-GEO ]   PTCH2 [ EBI - ARRAY_EXPRESS ]   PTCH2 [ SEEK ]   PTCH2 [ MEM ]
    Gene Expression Viewer (FireBrowse)PTCH2 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)8643
    GTEX Portal (Tissue expression)PTCH2
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9Y6C5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ9Y6C5  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ9Y6C5
    Splice isoforms : SwissVarQ9Y6C5
    PhosPhoSitePlusQ9Y6C5
    Domaine pattern : Prosite (Expaxy)SSD (PS50156)   
    Domains : Interpro (EBI)Ptc/Disp    SSD    TM_rcpt_patched   
    Domain families : Pfam (Sanger)Patched (PF02460)    Sterol-sensing (PF12349)   
    Domain families : Pfam (NCBI)pfam02460    pfam12349   
    Conserved Domain (NCBI)PTCH2
    DMDM Disease mutations8643
    Blocks (Seattle)PTCH2
    SuperfamilyQ9Y6C5
    Human Protein AtlasENSG00000117425
    Peptide AtlasQ9Y6C5
    HPRD04722
    IPIIPI00419647   IPI00471943   IPI00844378   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9Y6C5
    IntAct (EBI)Q9Y6C5
    FunCoupENSG00000117425
    BioGRIDPTCH2
    STRING (EMBL)PTCH2
    ZODIACPTCH2
    Ontologies - Pathways
    QuickGOQ9Y6C5
    Ontology : AmiGOcell fate determination  smoothened binding  signal transduction  hedgehog receptor activity  epidermal cell fate specification  integral component of membrane  hair cycle  skin development  positive regulation of epidermal cell differentiation  negative regulation of smoothened signaling pathway  hedgehog family protein binding  hedgehog family protein binding  
    Ontology : EGO-EBIcell fate determination  smoothened binding  signal transduction  hedgehog receptor activity  epidermal cell fate specification  integral component of membrane  hair cycle  skin development  positive regulation of epidermal cell differentiation  negative regulation of smoothened signaling pathway  hedgehog family protein binding  hedgehog family protein binding  
    Pathways : KEGGHedgehog signaling pathway    Pathways in cancer    Basal cell carcinoma   
    REACTOMEQ9Y6C5 [protein]
    REACTOME PathwaysR-HSA-373080 [pathway]   
    NDEx NetworkPTCH2
    Atlas of Cancer Signalling NetworkPTCH2
    Wikipedia pathwaysPTCH2
    Orthology - Evolution
    OrthoDB8643
    GeneTree (enSembl)ENSG00000117425
    Phylogenetic Trees/Animal Genes : TreeFamPTCH2
    HOVERGENQ9Y6C5
    HOGENOMQ9Y6C5
    Homologs : HomoloGenePTCH2
    Homology/Alignments : Family Browser (UCSC)PTCH2
    Gene fusions - Rearrangements
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerPTCH2 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)PTCH2
    dbVarPTCH2
    ClinVarPTCH2
    1000_GenomesPTCH2 
    Exome Variant ServerPTCH2
    ExAC (Exome Aggregation Consortium)PTCH2 (select the gene name)
    Genetic variants : HAPMAP8643
    Genomic Variants (DGV)PTCH2 [DGVbeta]
    DECIPHERPTCH2 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisPTCH2 
    Mutations
    ICGC Data PortalPTCH2 
    TCGA Data PortalPTCH2 
    Broad Tumor PortalPTCH2
    OASIS PortalPTCH2 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICPTCH2  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDPTCH2
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch PTCH2
    DgiDB (Drug Gene Interaction Database)PTCH2
    DoCM (Curated mutations)PTCH2 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)PTCH2 (select a term)
    intoGenPTCH2
    NCG5 (London)PTCH2
    Cancer3DPTCH2(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM109400    155255    603673    605462   
    Orphanet207    17074   
    MedgenPTCH2
    Genetic Testing Registry PTCH2
    NextProtQ9Y6C5 [Medical]
    TSGene8643
    GENETestsPTCH2
    Target ValidationPTCH2
    Huge Navigator PTCH2 [HugePedia]
    snp3D : Map Gene to Disease8643
    BioCentury BCIQPTCH2
    ClinGenPTCH2
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD8643
    Chemical/Pharm GKB GenePA33938
    Clinical trialPTCH2
    Miscellaneous
    canSAR (ICR)PTCH2 (select the gene name)
    Probes
    Litterature
    PubMed16 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMinePTCH2
    EVEXPTCH2
    GoPubMedPTCH2
    iHOPPTCH2
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Mon Sep 25 18:37:14 CEST 2017

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