imported>Ffffrr: Adding local short description: "Transmembrane protein receptor", overriding Wikidata description "InterPro Family" (Shortdesc helper)

2022-03-28T03:03:27Z

Adding local short description: "Transmembrane protein receptor", overriding Wikidata description "InterPro Family" (Shortdesc helper)

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{{Short description|Transmembrane protein receptor}}
{{Other uses of|Patch}}
{{infobox protein
| name = [[PTCH1|patched 1]]
| caption =
| image =
| width =
| HGNCid = 9585
| Symbol = [[PTCH1]]
| AltSymbols = NBCCS, PTCH
| EntrezGene = 5727
| OMIM = 601309
| RefSeq = NM_000264
| UniProt = Q13635
|| Chromosome = 9
| Arm = q
| Band = 22.1
| LocusSupplementaryData = q31
}}
{{infobox protein
| name = [[PTCH2|patched 2]]
| caption =
| image =
| width =
| HGNCid = 9586
| Symbol = [[PTCH2]]
| AltSymbols =
| EntrezGene = 8643
| OMIM = 603673
| RefSeq = NM_003738
| UniProt = Q9Y6C5
| Chromosome = 1
| Arm = p
| Band = 34.1
| LocusSupplementaryData =
}}
'''Patched''' (Ptc) is a [[conserved sequence|conserved]] 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the [[Hedgehog signaling pathway]] in insects and vertebrates. Patched is an essential gene in [[Drosophila embryogenesis|embryogenesis]] for proper [[Segmentation (biology)|segmentation]] in the fly [[embryo]], mutations in which may be embryonic lethal. Patched functions as the receptor for the Hedgehog protein <ref name="pmid1653906">{{cite journal |vauthors=Ingham PW, Taylor AM, Nakano Y | title = Role of the Drosophila patched gene in positional signalling | journal = Nature | volume = 353 | issue = 6340 | pages = 184–7 | year = 1991 | pmid = 1653906 | doi = 10.1038/353184a0 | bibcode = 1991Natur.353..184I | s2cid = 4361236 }}</ref> and controls its spatial distribution, in part via endocytosis of bound Hedgehog protein, which is then targeted for lysosomal degradation.<ref name="pmid15102702">{{cite journal |vauthors=Torroja C, Gorfinkiel N, Guerrero I | title = Patched controls the Hedgehog gradient by endocytosis in a dynamin-dependent manner, but this internalization does not play a major role in signal transduction | journal = Development | volume = 131 | issue = 10 | pages = 2395–408 | year = 2004 | pmid = 15102702 | doi = 10.1242/dev.01102 | doi-access = free }}</ref>

== Discovery ==

The original mutations in the ''ptc'' gene were discovered in the fruit fly ''[[Drosophila melanogaster]]'' by 1995 [[Nobel Laureates]] [[Eric F. Wieschaus]] and [[Christiane Nusslein-Volhard]] and colleagues, and the gene was independently cloned in 1989 by Joan Hooper in the laboratory of [[Matthew P. Scott]], and by [[Philip Ingham]] and colleagues.

== Role in hedgehog signaling ==

Patched is part of a [[negative feedback]] mechanism for hedgehog signaling that helps shape the spatial gradient of signaling activity across tissues. In the absence of hedgehog, low levels of patched are sufficient to suppress activity of the signal transduction pathway. When hedgehog is present, its [[cholesterol]] moiety binds to the [[sterol-sensing domain]] in patched, which then inhibits the activity of [[smoothened]]. Smoothened is a [[G protein-coupled receptor]], most of which is stored in membrane bound vesicles internally within the cell and which increases at the cell surface when hedgehog is present. Smoothened must be present on the [[cell membrane]] in order for the Hedgehog signaling pathway to be activated. Among other genes, the transcription of the patched gene is induced by hedgehog signaling, with the accumulation of the patched protein limiting signaling through the Smoothened protein. Recent work implicates the [[cilium]] in intracellular trafficking of hedgehog signaling components in vertebrate cells.

== Role in disease ==

Mutated patched proteins have been implicated in a number of cancers including [[basal cell carcinoma]], [[medulloblastoma]], and [[rhabdomyosarcoma]].<ref name="pmid14737121">{{cite journal |vauthors=Pasca di Magliano M, Hebrok M | title = Hedgehog signalling in cancer formation and maintenance | journal = Nat. Rev. Cancer | volume = 3 | issue = 12 | pages = 903–11 | year = 2003 | pmid = 14737121 | doi = 10.1038/nrc1229 | s2cid = 34050826 }}</ref> Hereditary [[mutation]]s in the human patched homolog ''[[PTCH1]]'' cause autosomal dominant [[Gorlin syndrome]], which consists of overgrowth and hereditary disposition to cancer including basal cell carcinoma and medulloblastoma. Mice with mutations in mouse ''PTCH1'' similarly develop medulloblastoma.

== References ==
{{reflist}}

[[Category:Hedgehog signaling pathway]]
[[Category:Human proteins]]
[[Category:Histopathology]]
[[Category:Developmental genes and proteins]]

Patched - Revision history

imported>Ffffrr: Adding local short description: "Transmembrane protein receptor", overriding Wikidata description "InterPro Family" (Shortdesc helper)