Ptch1
entrez
19206
canonical
uniprot
Q61115
canonical
ensembl
ENSMUSG00000021466
resolver
ensp
ENSMUSP00000021921
resolver
ensp
ENSMUSP00000141489
resolver
enst
ENSMUST00000021921
resolver
genesymbol
Ptch1
resolver
genesymbol_syn
PTCH
resolver
genesymbol_syn
Ptch
resolver
uniprot
Q3TQB0
resolver
uniprot
Q3UUD4
resolver
uniprot
Q5R252
resolver
uniprot_entry
PTC1_MOUSE
resolver
uniprot_entry
Q3TQB0_MOUSE
resolver
uniprot_entry
Q3UUD4_MOUSE
resolver
uniprot_entry
Q5R252_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Specifically inhibited by nanobody TI23. {ECO:0000269|PubMed:33139559}.
uniprot
proteins
amino_acid_sequence
MASAGNAAGALGRQAGGGRRRRTGGPHRAAPDRDYLHRPSYCDAAFALEQISKGKATGRKAPLWLRAKFQRLLFKLGCYIQKNCGKFLVVGLLIFGAFAVGLKAANLETNVEELWVEVGGRVSRELNYTRQKIGEEAMFNPQLMIQTPKEEGANVLTTEALLQHLDSALQASRVHVYMYNRQWKLEHLCYKSGELITETGYMDQIIEYLYPCLIITPLDCFWEGAKLQSGTAYLLGKPPLRWTNFDPLEFLEELKKINYQVDSWEEMLNKAEVGHGYMDRPCLNPADPDCPATAPNKNSTKPLDVALVLNGGCQGLSRKYMHWQEELIVGGTVKNATGKLVSAHALQTMFQLMTPKQMYEHFRGYDYVSHINWNEDRAAAILEAWQRTYVEVVHQSVAPNSTQKVLPFTTTTLDDILKSFSDVSVIRVASGYLLMLAYACLTMLRWDCSKSQGAVGLAGVLLVALSVAAGLGLCSLIGISFNAATTQVLPFLALGVGVDDVFLLAHAFSETGQNKRIPFEDRTGECLKRTGASVALTSISNVTAFFMAALIPIPALRAFSLQAAVVVVFNFAMVLLIFPAILSMDLYRREDRRLDIFCCFTSPCVSRVIQVEPQAYTEPHSNTRYSPPPPYTSHSFAHETHITMQSTVQLRTEYDPHTHVYYTTAEPRSEISVQPVTVTQDNLSCQSPESTSSTRDLLSQFSDSSLHCLEPPCTKWTLSSFAEKHYAPFLLKPKAKVVVILLFLGLLGVSLYGTTRVRDGLDLTDIVPRETREYDFIAAQFKYFSFYNMYIVTQKADYPNIQHLLYDLHKSFSNVKYVMLEENKQLPQMWLHYFRDWLQGLQDAFDSDWETGRIMPNNYKNGSDDGVLAYKLLVQTGSRDKPIDISQLTKQRLVDADGIINPSAFYIYLTAWVSNDPVAYAASQANIRPHRPEWVHDKADYMPETRLRIPAAEPIEYAQFPFYLNGLRDTSDFVEAIEKVRVICNNYTSLGLSSYPNGYPFLFWEQYISLRHWLLLSISVVLACTFLVCAVFLLNPWTAGIIVMVLALMTVELFGMMGLIGIKLSAVPVVILIASVGIGVEFTVHVALAFLTAIGDKNHRAMLALEHMFAPVLDGAVSTLLGVLMLAGSEFDFIVRYFFAVLAILTVLGVLNGLVLLPVLLSFFGPCPEVSPANGLNRLPTPSPEPPPSVVRFAVPPGHTNNGSDSSDSEYSSQTTVSGISEELRQYEAQQGAGGPAHQVIVEATENPVFARSTVVHPDSRHQPPLTPRQQPHLDSGSLSPGRQGQQPRRDPPREGLRPPPYRPRRDAFEISTEGHSGPSNRDRSGPRGARSHNPRNPTSTAMGSSVPSYCQPITTVTASASVTVAVHPPPGPGRNPRGGPCPGYESYPETDHGVFEDPHVPFHVRCERRDSKVEVIELQDVECEERPWGSSSN
uniprot
proteins
function
FUNCTION: Negative regulator of the smoothened signaling pathway, which acts as a receptor for hedgehog (SHH, IHH and DHH) morphogens (PubMed:12192414, PubMed:17641202, PubMed:21537345, PubMed:21931618, PubMed:27552050, PubMed:30415841, PubMed:33139559, PubMed:9262482). In absence of hedgehog, acts as an inhibitor of smoothened protein (SMO) by preventing SMO access to cholesterol: mechanistically, acts as a cholesterol transporter, which depeletes cholesterol from the outer leaflet of plasma membrane, thereby preventing cholesterol-binding to the extracellular CRD region of SMO (PubMed:30415841, PubMed:31657721, PubMed:34698632). Hedgehog-binding inhibits PTCH1 cholesterol transporter activity, promoting SMO activation by cholesterol and transduction of the smoothened signaling pathway (PubMed:30819883). Molecular mechanism governing cholesterol transport are still unclear: may move cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium or sodium ion export in the opposite direction (PubMed:30415841, PubMed:34698632). {ECO:0000269|PubMed:12192414, ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:21537345, ECO:0000269|PubMed:21931618, ECO:0000269|PubMed:27552050, ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:30819883, ECO:0000269|PubMed:31657721, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34698632, ECO:0000269|PubMed:9262482}.
uniprot
proteins
mass_dalton
159273
uniprot
proteins
mutagenesis
MUTAGEN 111..115; /note="VEELW->FEEFA: Impaired ability to inhibit smoothened signaling pathway without affecting hedgehog-binding."; /evidence="ECO:0000269|PubMed:30415841"; MUTAGEN 111..114; /note="VEEL->FEEF: Impaired ability to inhibit smoothened signaling pathway without affecting hedgehog-binding; when associated with F-111."; /evidence="ECO:0000269|PubMed:30415841"; MUTAGEN 111; /note="V->F: Impaired ability to inhibit smoothened signaling pathway without affecting hedgehog-binding; when associated with F-766. Impaired ability to inhibit smoothened signaling pathway without affecting hedgehog-binding; when associated with 111-F--F-114."; /evidence="ECO:0000269|PubMed:30415841"; MUTAGEN 472; /note="G->R: Loss-of-function; abolished ability to inhibit smoothened."; /evidence="ECO:0000269|PubMed:28344083"; MUTAGEN 628..631; /note="Missing: Abolished endocytic sorting, leading to accumulation in cilia due to impaired ubiquitination by SMURF1 and/or SMURF2; when associated with deletion of 1299-P--Y-1302."; /evidence="ECO:0000269|PubMed:24925320"; MUTAGEN 766; /note="I->F: Impaired ability to inhibit smoothened signaling pathway without affecting hedgehog-binding; when associated with F-111."; /evidence="ECO:0000269|PubMed:30415841"; MUTAGEN 1299..1302; /note="Missing: Abolished endocytic sorting, leading to accumulation in cilia due to impaired ubiquitination by SMURF1 and/or SMURF2; when associated with deletion of 628-P--Y-631."; /evidence="ECO:0000269|PubMed:24925320"; MUTAGEN 1413; /note="K->R: Accumulates at the plasma membrane, increased half-life and increased CASP9-mediated cell death."; /evidence="ECO:0000269|PubMed:25092867
uniprot
proteins
post_translational_modification
PTM: In the absence of hedgehog (SHH, IHH and DHH) ligands, ubiquitination by ITCH at Lys-1413 promotes endocytosis and both proteasomal and lysosomal degradation (PubMed:25092867). Ubiquitinated by SMURF1 and/or SMURF2 in response to SHH, promoting endocytosis and lysosomal degradation; degradation is essential for PTCH1 clearance from the primary cilium and smoothened pathway activation (PubMed:24925320). {ECO:0000269|PubMed:24925320, ECO:0000269|PubMed:25092867}.
uniprot
proteins
protein_family
Patched family
uniprot
proteins
pubmed
12192414
uniprot
proteins
pubmed
17641202
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21537345
uniprot
proteins
pubmed
21931618
uniprot
proteins
pubmed
24062445
uniprot
proteins
pubmed
24925320
uniprot
proteins
pubmed
25092867
uniprot
proteins
pubmed
27552050
uniprot
proteins
pubmed
28344083
uniprot
proteins
pubmed
30415841
uniprot
proteins
pubmed
30819883
uniprot
proteins
pubmed
31657721
uniprot
proteins
pubmed
33139559
uniprot
proteins
pubmed
34174188
uniprot
proteins
pubmed
34698632
uniprot
proteins
pubmed
35658032
uniprot
proteins
pubmed
8595881
uniprot
proteins
pubmed
9262482
uniprot
proteins
sequence_length
1434
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21931618, ECO:0000269|PubMed:24062445, ECO:0000269|PubMed:30819883}; Multi-pass membrane protein {ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188}. Cell projection, cilium membrane {ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:24925320, ECO:0000269|PubMed:30819883}; Multi-pass membrane protein {ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188}. Note=Localizes to primary cilium and prevents cilium localization of SMO (PubMed:17641202, PubMed:30819883). Delocalizes from primary cilium following hedgehog-binding (PubMed:30819883). {ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:30819883}.
uniprot
proteins
transmembrane_region
TRANSMEM 80..103; /note="Helical; Name=TM1"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65"; TRANSMEM 425..445; /note="Helical; Name=TM2"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 453..477; /note="Helical; Name=TM3"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 487..506; /note="Helical; Name=TM4"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 530..550; /note="Helical; Name=TM5"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 559..582; /note="Helical; Name=TM6"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 732..754; /note="Helical; Name=TM7"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 1014..1035; /note="Helical; Name=TM8"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 1037..1060; /note="Helical; Name=TM9"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 1068..1088; /note="Helical; Name=TM10"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 1108..1128; /note="Helical; Name=TM11"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z"; TRANSMEM 1138..1164; /note="Helical; Name=TM12"; /evidence="ECO:0000269|PubMed:30415841, ECO:0000269|PubMed:33139559, ECO:0000269|PubMed:34174188, ECO:0007744|PDB:6MG8, ECO:0007744|PDB:7K65, ECO:0007744|PDB:7V6Y, ECO:0007744|PDB:7V6Z
uniprot
proteins