# Patched

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Transmembrane protein receptor

For other uses of "Patch", see [Patch (disambiguation)](/source/Patch_(disambiguation)).

patched 1 Identifiers Symbol PTCH1 Alt. symbols NBCCS, PTCH NCBI gene 5727 HGNC 9585 OMIM 601309 RefSeq NM_000264 UniProt Q13635 Other data Locus Chr. 9 q22.1q31 Search for Structures Swiss-model Domains InterPro

patched 2 Identifiers Symbol PTCH2 NCBI gene 8643 HGNC 9586 OMIM 603673 RefSeq NM_003738 UniProt Q9Y6C5 Other data Locus Chr. 1 p34.1 Search for Structures Swiss-model Domains InterPro

**Patched** (Ptc) is a [conserved](/source/Conserved_sequence) 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the [Hedgehog signaling pathway](/source/Hedgehog_signaling_pathway) in insects and vertebrates. Patched is an essential gene in [embryogenesis](/source/Drosophila_embryogenesis) for proper [segmentation](/source/Segmentation_(biology)) in the fly [embryo](/source/Embryo), mutations in which may be embryonic lethal. Patched functions as the receptor for the Hedgehog protein [1] and controls its spatial distribution, in part via endocytosis of bound Hedgehog protein, which is then targeted for lysosomal degradation.[2]

## Discovery

The original mutations in the *ptc* gene were discovered in the fruit fly *[Drosophila melanogaster](/source/Drosophila_melanogaster)* by 1995 [Nobel Laureates](/source/Nobel_Laureates) [Eric F. Wieschaus](/source/Eric_F._Wieschaus) and [Christiane Nusslein-Volhard](/source/Christiane_Nusslein-Volhard) and colleagues, and the gene was independently cloned in 1989 by Joan Hooper in the laboratory of [Matthew P. Scott](/source/Matthew_P._Scott), and by [Philip Ingham](/source/Philip_Ingham) and colleagues.

## Role in hedgehog signaling

Patched is part of a [negative feedback](/source/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](/source/Cholesterol) moiety binds to the [sterol-sensing domain](/source/Sterol-sensing_domain) in patched, which then inhibits the activity of [smoothened](/source/Smoothened). Smoothened is a [G protein-coupled receptor](/source/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](/source/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](/source/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](/source/Basal_cell_carcinoma), [medulloblastoma](/source/Medulloblastoma), and [rhabdomyosarcoma](/source/Rhabdomyosarcoma).[3] Hereditary [mutations](/source/Mutation) in the human patched homolog *[PTCH1](/source/PTCH1)* cause autosomal dominant [Gorlin syndrome](/source/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

1. **[^](#cite_ref-pmid1653906_1-0)** Ingham PW, Taylor AM, Nakano Y (1991). "Role of the Drosophila patched gene in positional signalling". *Nature*. **353** (6340): 184–7. [Bibcode](/source/Bibcode_(identifier)):[1991Natur.353..184I](https://ui.adsabs.harvard.edu/abs/1991Natur.353..184I). [doi](/source/Doi_(identifier)):[10.1038/353184a0](https://doi.org/10.1038%2F353184a0). [PMID](/source/PMID_(identifier)) [1653906](https://pubmed.ncbi.nlm.nih.gov/1653906). [S2CID](/source/S2CID_(identifier)) [4361236](https://api.semanticscholar.org/CorpusID:4361236).

1. **[^](#cite_ref-pmid15102702_2-0)** Torroja C, Gorfinkiel N, Guerrero I (2004). ["Patched controls the Hedgehog gradient by endocytosis in a dynamin-dependent manner, but this internalization does not play a major role in signal transduction"](https://doi.org/10.1242%2Fdev.01102). *Development*. **131** (10): 2395–408. [doi](/source/Doi_(identifier)):[10.1242/dev.01102](https://doi.org/10.1242%2Fdev.01102). [PMID](/source/PMID_(identifier)) [15102702](https://pubmed.ncbi.nlm.nih.gov/15102702).

1. **[^](#cite_ref-pmid14737121_3-0)** Pasca di Magliano M, Hebrok M (2003). "Hedgehog signalling in cancer formation and maintenance". *Nat. Rev. Cancer*. **3** (12): 903–11. [doi](/source/Doi_(identifier)):[10.1038/nrc1229](https://doi.org/10.1038%2Fnrc1229). [PMID](/source/PMID_(identifier)) [14737121](https://pubmed.ncbi.nlm.nih.gov/14737121). [S2CID](/source/S2CID_(identifier)) [34050826](https://api.semanticscholar.org/CorpusID:34050826).

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Adapted from the Wikipedia article [Patched](https://en.wikipedia.org/wiki/Patched) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Patched?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.