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homolog of drosophila patched protein 1; PTC protein-1; patched homolog protein 1 (PTC1, PTCH1)
Function:
- transcriptional repression of members of Wnt & TGF-beta gene families
- action of PTC1 is opposed by hedgehog
- acts as a receptor for
a) sonic hedgehog (SHH)
b) Indian hedgehog (IHH)
c) desert hedgehog (DHH)
- associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal
- seems to have a tumor suppressor function; inactivation of PTCH1 is probably a necessary, if not sufficient for tumorigenesis
- glycosylation is necessary for SHH binding (putative)
- interacts with SNX17
Structure:
- belongs to the patched family
- contains 1 SSD (sterol-sensing) domain
Compartment: membrane
Expression:
- in the adult, expressed in brain, lung, liver, heart, placenta, skeletal muscle, pancreas & kidney
- expressed in tumor cells but not in normal skin
- in the embryo, found in all major target tissues of sonic hedgehog, such as the ventral neural tube, somites, & tissues surrounding the zone of polarizing activity of the limb bud
Pathology:
- defects in PTCH1 are probably the cause of basal cell nevus syndrome; may be associated with large body size
- PTCH1 is also mutated in squamous cell carcinoma of the skin
- defects in PTCH1 are a cause of sporadic basal cell carcinoma
- defects in PTCH1 are the cause of holoprosencephaly type 7
General
homolog of drosophila patched protein (PTC)
Properties
SIZE: MW = 161 kD
entity length = 1447 aa
COMPARTMENT: cellular membrane
MOTIF: cytoplasmic domain {1-100}
MOTIF: calponin homology domain
NAME: calponin homology domain
SITE: 14-31
transmembrane domain {101-121}
exoplasmic loop {122-436}
MOTIF: N-glycosylation site {N141}
N-glycosylation site {N312}
N-glycosylation site {N349}
N-glycosylation site {N414}
transmembrane domain {437-457}
cytoplasmic loop {458-472}
transmembrane domain {473-493}
exoplasmic loop {494-501}
transmembrane domain {502-522}
cytoplasmic loop {523-547}
transmembrane domain {548-568}
exoplasmic loop {569-577}
transmembrane domain {578-598}
cytoplasmic loop {599-748}
transmembrane domain {749-769}
exoplasmic loop {770-1027}
MOTIF: N-glycosylation site {N875}
N-glycosylation site {N1000}
transmembrane domain {1028-1048}
cytoplasmic loop {1049-1055}
transmembrane domain {1056-1076}
exoplasmic loop {1077-1083}
transmembrane domain {1084-1104}
cytoplasmic loop {1105-1121}
transmembrane domain {1122-1141}
exoplasmic loop {1142-1154}
transmembrane domain {1155-1175}
cytoplasmic domain {1176-1447}
References
- Hahn H et al
Mutations of the human homolog of Drosophila patched in the
nevoid basal cell carcinoma syndrome.
Cell. 1996 Jun 14;85(6):841-51.
PMID: 8681379
- Entrez Gene :accession 5727
- UniProt :accession Q13635
- PTCH1 mutation database
http://www.cybergene.se/PTCH/ptchbase.html
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/PTCH100.html
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/PTCH1
Databases & Figures
OMIM correlations
UniProt Q13635
Pfam PF02460
Entrez Gene 5727
Kegg hsa:5727
hedgehog/gli pathway