Reviewed,
UniProtKB/Swiss-Prot Q13635 (PTC1_HUMAN)
Last modified
February 9, 2010.
Version 104.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: Protein patched homolog 1 Short name=PTC1 Short name=PTC | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1447 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis. |
| Subunit structure | Interacts with SNX17. Ref.4 |
| Subcellular location | |
| Tissue specificity | In the adult, expressed in brain, lung, liver, heart, placenta, skeletal muscle, pancreas and kidney. Expressed in tumor cells but not in normal skin. |
| Developmental stage | In the embryo, found in all major target tissues of sonic hedgehog, such as the ventral neural tube, somites, and tissues surrounding the zone of polarizing activity of the limb bud. |
| Post-translational modification | Glycosylation is necessary for SHH binding By similarity. |
| Involvement in disease | Defects in PTCH1 are probably the cause of basal cell nevus syndrome (BCNS) [MIM:109400]; also known as Gorlin syndrome or Gorlin-Goltz syndrome. BCNS is an autosomal dominant disease characterized by nevoid basal cell carcinomas (NBCCS) and developmental abnormalities such as rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In addition, the patients suffer from a multitude of tumors like basal cell carcinomas (BCC), fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas. PTCH1 is also mutated in squamous cell carcinoma (SCC). Could also be associated with large body size observed in BCNS patients. Ref.5 Ref.6 Ref.9 Ref.11 Ref.15 Defects in PTCH1 are a cause of sporadic basal cell carcinoma (BCC) [MIM:605462]. Ref.9 Ref.1 Defects in PTCH1 are the cause of holoprosencephaly type 7 (HPE7) [MIM:610828]. Holoprosencephaly (HPE) [MIM:236100] is the most common structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Ref.13 Ref.16 Ref.17 |
| Sequence similarities | Belongs to the patched family. Contains 1 SSD (sterol-sensing) domain. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Membrane |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation Holoprosencephaly Tumor suppressor |
| Domain | Transmembrane |
| Molecular function | Receptor |
| PTM | Glycoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | embryonic limb morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of multicellular organism growthInferred from sequence or structural similarity. Source: UniProtKB protein processingInferred from sequence or structural similarity. Source: UniProtKB regulation of smoothened signaling pathwayInferred from sequence or structural similarity. Source: UniProtKB smoothened signaling pathwayInferred from sequence or structural similarity. Source: UniProtKB |
| Cellular component | integral to plasma membrane Ref.6 Traceable author statement. Source: ProtInc |
| Molecular function | hedgehog receptor activity Inferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1447 | 1447 | Protein patched homolog 1 | PRO_0000205964 | |||||
Regions | |||||||||
| Topological domain | 1 – 100 | 100 | Cytoplasmic Potential | ||||||
| Transmembrane | 101 – 121 | 21 | Potential | ||||||
| Topological domain | 122 – 436 | 315 | Extracellular Potential | ||||||
| Transmembrane | 437 – 457 | 21 | Potential | ||||||
| Topological domain | 458 – 472 | 15 | Cytoplasmic Potential | ||||||
| Transmembrane | 473 – 493 | 21 | Potential | ||||||
| Topological domain | 494 – 501 | 8 | Extracellular Potential | ||||||
| Transmembrane | 502 – 522 | 21 | Potential | ||||||
| Topological domain | 523 – 547 | 25 | Cytoplasmic Potential | ||||||
| Transmembrane | 548 – 568 | 21 | Potential | ||||||
| Topological domain | 569 – 577 | 9 | Extracellular Potential | ||||||
| Transmembrane | 578 – 598 | 21 | Potential | ||||||
| Topological domain | 599 – 748 | 150 | Cytoplasmic Potential | ||||||
| Transmembrane | 749 – 769 | 21 | Potential | ||||||
| Topological domain | 770 – 1027 | 258 | Extracellular Potential | ||||||
| Transmembrane | 1028 – 1048 | 21 | Potential | ||||||
| Topological domain | 1049 – 1055 | 7 | Cytoplasmic Potential | ||||||
| Transmembrane | 1056 – 1076 | 21 | Potential | ||||||
| Topological domain | 1077 – 1083 | 7 | Extracellular Potential | ||||||
| Transmembrane | 1084 – 1104 | 21 | Potential | ||||||
| Topological domain | 1105 – 1121 | 17 | Cytoplasmic Potential | ||||||
| Transmembrane | 1122 – 1141 | 20 | Potential | ||||||
| Topological domain | 1142 – 1154 | 13 | Extracellular Potential | ||||||
| Transmembrane | 1155 – 1175 | 21 | Potential | ||||||
| Topological domain | 1176 – 1447 | 272 | Cytoplasmic Potential | ||||||
| Domain | 438 – 598 | 161 | SSD | ||||||
| Compositional bias | 14 – 31 | 18 | Gly-rich | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 141 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 312 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 349 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 414 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 875 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 1000 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 175 | 1 | L → P in BCNS; sporadic BCC. Ref.1 | VAR_007843 | |||||
| Natural variant | 230 | 1 | T → P in BCNS. Ref.15 | VAR_020845 | |||||
| Natural variant | 376 | 1 | F → S in BCNS. Ref.9 | VAR_007844 | |||||
| Natural variant | 393 | 1 | A → T in HPE7. Ref.13 | VAR_032952 | |||||
| Natural variant | 443 | 1 | A → G in HPE7. Ref.17 | VAR_032953 | |||||
| Natural variant | 505 – 506 | 2 | FL → LR in BCNS. | VAR_020846 | |||||
| Natural variant | 509 | 1 | G → R in BCNS; could be a rare polymorphism. Ref.5 | VAR_010974 | |||||
| Natural variant | 509 | 1 | G → V in BCNS. Ref.5 | VAR_010975 | |||||
| Natural variant | 513 | 1 | D → Y in BCNS. Ref.6 | VAR_010976 | |||||
| Natural variant | 728 | 1 | T → M in HPE7. dbSNP rs28936404. Ref.13 Ref.16 | VAR_032954 | |||||
| Natural variant | 751 | 1 | V → G in HPE7. Ref.17 | VAR_032955 | |||||
| Natural variant | 815 | 1 | I → IPNI in BCNS. | VAR_007845 | |||||
| Natural variant | 816 | 1 | Missing in BCNS. | VAR_010977 | |||||
| Natural variant | 827 | 1 | S → G in HPE7. Ref.13 | VAR_032956 | |||||
| Natural variant | 829 | 1 | V → M in squamous cell carcinoma. Ref.12 | VAR_010978 | |||||
| Natural variant | 908 | 1 | V → G in HPE7. Ref.17 | VAR_032957 | |||||
| Natural variant | 1052 | 1 | T → M in HPE7. dbSNP rs28936405. Ref.13 Ref.17 | VAR_032958 | |||||
| Natural variant | 1069 | 1 | G → R in BCNS. Ref.6 | VAR_010979 | |||||
| Natural variant | 1083 | 1 | V → VV in BCNS. Ref.9 | VAR_007846 | |||||
| Natural variant | 1114 | 1 | R → W in BCNS and BCC. Ref.9 | VAR_007847 | |||||
| Natural variant | 1132 | 1 | S → P in BCNS. Ref.11 | VAR_010980 | |||||
| Natural variant | 1132 | 1 | S → Y in BCNS. Ref.5 | VAR_010981 | |||||
| Natural variant | 1195 | 1 | T → S: dbSNP rs2236405. | VAR_020440 | |||||
| Natural variant | 1242 | 1 | E → K in squamous cell carcinoma. Ref.12 | VAR_010982 | |||||
| Natural variant | 1282 | 1 | P → L: dbSNP rs2227968. | VAR_020847 | |||||
| Natural variant | 1315 | 1 | P → L: dbSNP rs357564. Ref.1 Ref.3 Ref.8 Ref.10 | VAR_010983 | |||||
| Natural variant | 1438 | 1 | E → D in BCNS; sporadic NBCCS. Ref.7 | VAR_010984 | |||||
Experimental info | |||||||||
| Sequence conflict | 1109 | 1 | G → S in AAC50496. Ref.2 | ||||||
| Sequence conflict | 1144 | 1 | E → D in AAC50496. Ref.2 | ||||||
| Sequence conflict | 1175 | 1 | L → W in AAC50496. Ref.2 | ||||||
| Sequence conflict | 1283 | 1 | R → K in AAC50496. Ref.2 | ||||||
| Sequence conflict | 1309 | 1 | E → K in AAC50496. Ref.2 | ||||||
| Sequence conflict | 1353 | 1 | A → T in AAC50496. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human homolog of patched, a candidate gene for the basal cell nevus syndrome." Johnson R.L., Rothman A.L., Xie J., Goodrich L.V., Bare J.W., Bonifas J.M., Quinn A.G., Myers R.M., Cox D.R., Epstein E.H. Jr., Scott M.P. Science 272:1668-1671(1996) [PubMed: 8658145] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS BCC PRO-175; PRO-ASN-ILE-815 INS AND LEU-1315. Tissue: Lung. |
| [2] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities." Hahn H., Christiansen J., Wicking C., Zaphiropolous P.G., Chidambaram A., Gerrard B., Vorechovsky I., Bale A.E., Toftgard R., Dean M., Wainwright B.J. J. Biol. Chem. 271:12125-12128(1996) [PubMed: 8647801] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 152-1447, VARIANT LEU-1315. Tissue: Fetal brain. |
| [4] | "Functions of sorting nexin 17 domains and recognition motif for P-selectin trafficking." Knauth P., Schlueter T., Czubayko M., Kirsch C., Florian V., Schreckenberger S., Hahn H., Bohnensack R. J. Mol. Biol. 347:813-825(2005) [PubMed: 15769472] [Abstract] Cited for: INTERACTION WITH SNX17. |
| [5] | "Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients." Chidambaram A., Goldstein A.M., Gailani M.R., Gerrard B., Bale S.J., DiGiovanna J.J., Bale A.E., Dean M. Cancer Res. 56:4599-4601(1996) [PubMed: 8840969] [Abstract] Cited for: VARIANTS BCNS ARG-509; VAL-509; GLN-816 DEL AND TYR-1132. |
| [6] | "Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident." Wicking C., Shanley S., Smyth I., Gillies S., Negus K., Graham S., Suthers G., Haites N., Edwards M., Wainwright B.J., Chenevix-Trench G. Am. J. Hum. Genet. 60:21-26(1997) [PubMed: 8981943] [Abstract] Cited for: VARIANTS BCNS TYR-513 AND ARG-1069. |
| [7] | "Characterisation of human patched germ line mutations in naevoid basal cell carcinoma syndrome." Lench N.J., Telford E.A.R., High A.S., Markham A.F., Wicking C., Wainwright B.J. Hum. Genet. 100:497-502(1997) [PubMed: 9341860] [Abstract] Cited for: VARIANT NBCCS ASP-1438. |
| [8] | "Gorlin syndrome: identification of 4 novel germ-line mutations of the human patched (PTCH) gene." Hasenpusch-Theil K., Bataille V., Laehdetie J., Obermayr F., Sampson J.R., Frischauf A.-M. Hum. Mutat. 11:480-480(1998) [PubMed: 10200051] [Abstract] Cited for: VARIANT LEU-1315. |
| [9] | "Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome." Aszterbaum M., Rothman A.L., Johnson R.L., Fisher M., Xie J., Bonifas J.M., Zhang X., Scott M.P., Epstein E.H. Jr. J. Invest. Dermatol. 110:885-888(1998) [PubMed: 9620294] [Abstract] Cited for: VARIANTS BCNS SER-376 AND VAL-1083 INS, VARIANT BCC TRP-1114. |
| [10] | "Identification of PATCHED mutations in medulloblastomas by direct sequencing." Dong J., Gailani M.R., Pomeroy S.L., Reardon D., Bale A.E. Hum. Mutat. 16:89-90(2000) [PubMed: 10874314] [Abstract] Cited for: VARIANT LEU-1315. |
| [11] | "Coincident PTCH and BRCA1 germline mutations in a patient with nevoid basal cell carcinoma syndrome and familial breast cancer." Reifenberger J., Arnold N., Kiechle M., Reifenberger G., Hauschild A. J. Invest. Dermatol. 116:472-474(2001) [PubMed: 11231326] [Abstract] Cited for: VARIANT BCNS PRO-1132. |
| [12] | "PTCH mutations in squamous cell carcinoma of the skin." Ping X.L., Ratner D., Zhang H., Wu X.L., Zhang M.J., Chen F.F., Silvers D.N., Peacocke M., Tsou H.C. J. Invest. Dermatol. 116:614-616(2001) [PubMed: 11286632] [Abstract] Cited for: VARIANTS SQUAMOUS CELL CARCINOMA MET-829 AND LYS-1242. |
| [13] | "Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly." Ming J.E., Kaupas M.E., Roessler E., Brunner H.G., Golabi M., Tekin M., Stratton R.F., Sujansky E., Bale S.J., Muenke M. Hum. Genet. 110:297-301(2002) [PubMed: 11941477] [Abstract] Cited for: VARIANTS HPE7 THR-393; MET-728; GLY-827 AND MET-1052. |
| [14] | Erratum Ming J.E., Kaupas M.E., Roessler E., Brunner H.G., Golabi M., Tekin M., Stratton R.F., Sujansky E., Bale S.J., Muenke M. Hum. Genet. 111:464-464(2002) |
| [15] | "Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma syndrome patients: identification of thirteen novel alleles." Savino M., d'Apolito M., Formica V., Baorda F., Mari F., Renieri A., Carabba E., Tarantino E., Andreucci E., Belli S., Lo Muzio L., Dallapiccola B., Zelante L., Savoia A. Hum. Mutat. 24:441-441(2004) [PubMed: 15459969] [Abstract] Cited for: VARIANTS BCNS PRO-230 AND 505-LEU-ARG-506. |
| [16] | "GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum?" Rahimov F., Ribeiro L.A., de Miranda E., Richieri-Costa A., Murray J.C. Am. J. Med. Genet. A 140:2571-2576(2006) [PubMed: 17096318] [Abstract] Cited for: VARIANT HPE7 MET-728. |
| [17] | "PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI." Ribeiro L.A., Murray J.C., Richieri-Costa A. Am. J. Med. Genet. A 140:2584-2586(2006) [PubMed: 17001668] [Abstract] Cited for: VARIANTS HPE7 GLY-443; GLY-751; GLY-908 AND MET-1052. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U59464 mRNA. Translation: AAC50550.1. AL161729 Genomic DNA. Translation: CAH73817.1. U43148 mRNA. Translation: AAC50496.1. |
| IPI | IPI00014374. |
| RefSeq | NP_000255.2. NP_001077071.1. NP_001077072.1. NP_001077073.1. NP_001077074.1. NP_001077075.1. NP_001077076.1. |
| UniGene | Hs.494538 Hs.638946 |
3D structure databases | |
| SMR | Q13635. Positions 472-621, 1008-1180. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q13635. |
PTM databases | |
| PhosphoSite | Q13635. |
Proteomic databases | |
| PRIDE | Q13635. |
Genome annotation databases | |
| Ensembl | ENST00000331920; ENSP00000332353; ENSG00000185920; Homo sapiens. [Genome view] ENST00000375274; ENSP00000364423; ENSG00000185920; Homo sapiens. [Genome view] |
| GeneID | 5727. |
| KEGG | hsa:5727. |
| UCSC | uc004avk.2. human. |
Organism-specific databases | |
| CTD | 5727. |
| GeneCards | GC09M097246. |
| H-InvDB | HIX0025725. HIX0035051. |
| HGNC | HGNC:9585. PTCH1. |
| HPA | CAB013717. |
| MIM | 109400. phenotype. 601309. gene. 605462. phenotype. 610828. phenotype. |
| Orphanet | 377. Gorlin syndrome. 2162. Holoprosencephaly. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | HBG713504. |
| HOVERGEN | Q13635. |
| InParanoid | Q13635. |
| OMA | RPSYCDA. |
| PhylomeDB | Q13635. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | glypican_3pathway. Glypican 3 network. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins. hedgehog_2pathway. Signaling events mediated by the Hedgehog family. |
Gene expression databases | |
| ArrayExpress | Q13635. |
| Bgee | Q13635. |
| CleanEx | HS_PTCH1. |
| Genevestigator | Q13635. |
| GermOnline | ENSG00000185920. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR003392. Patched. IPR000731. SSD_5TM. IPR004766. TM_rcpt_patched. [Graphical view] |
| Pfam | PF02460. Patched. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR00918. 2A060602. 1 hit. |
| PROSITE | PS50156. SSD. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 22266. |
| SOURCE | Search... |
Entry information
| Entry name | PTC1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13635 Secondary accession number(s): Q13463, Q5VZC0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


