ID PTC1_HUMAN Reviewed; 1447 AA. AC Q13635; Q13463; Q5VZC0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 17-APR-2007, entry version 67. DE Protein patched homolog 1 (PTC1) (PTC). GN Name=PTCH1; Synonyms=PTCH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS BCC PRO-175 AND RP PRO-ASN-ILE-815 INS. RC TISSUE=Lung; RX MEDLINE=96247324; PubMed=8658145; RA Johnson R.L., Rothman A.L., Xie J., Goodrich L.V., Bare J.W., RA Bonifas J.M., Quinn A.G., Myers R.M., Cox D.R., Epstein E.H. Jr., RA Scott M.P.; RT "Human homolog of patched, a candidate gene for the basal cell nevus RT syndrome."; RL Science 272:1668-1671(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-1315. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 152-1447. RC TISSUE=Fetal brain; RX MEDLINE=96218118; PubMed=8647801; DOI=10.1074/jbc.271.21.12125; RA Hahn H., Christiansen J., Wicking C., Zaphiropolous P.G., RA Chidambaram A., Gerrard B., Vorechovsky I., Bale A.E., Toftgard R., RA Dean M., Wainwright B.J.; RT "A mammalian patched homolog is expressed in target tissues of sonic RT hedgehog and maps to a region associated with developmental RT abnormalities."; RL J. Biol. Chem. 271:12125-12128(1996). RN [4] RP INTERACTION WITH SNX17. RX PubMed=15769472; DOI=10.1016/j.jmb.2005.02.004; RA Knauth P., Schlueter T., Czubayko M., Kirsch C., Florian V., RA Schreckenberger S., Hahn H., Bohnensack R.; RT "Functions of sorting nexin 17 domains and recognition motif for P- RT selectin trafficking."; RL J. Mol. Biol. 347:813-825(2005). RN [5] RP VARIANTS BCNS ARG-509; VAL-509; GLN-816 DEL AND TYR-1132. RX MEDLINE=96438609; PubMed=8840969; RA Chidambaram A., Goldstein A.M., Gailani M.R., Gerrard B., Bale S.J., RA DiGiovanna J.J., Bale A.E., Dean M.; RT "Mutations in the human homologue of the Drosophila patched gene in RT Caucasian and African-American nevoid basal cell carcinoma syndrome RT patients."; RL Cancer Res. 56:4599-4601(1996). RN [6] RP VARIANTS BCNS TYR-513 AND ARG-1069. RX MEDLINE=97136566; PubMed=8981943; RA Wicking C., Shanley S., Smyth I., Gillies S., Negus K., Graham S., RA Suthers G., Haites N., Edwards M., Wainwright B.J., RA Chenevix-Trench G.; RT "Most germ-line mutations in the nevoid basal cell carcinoma syndrome RT lead to a premature termination of the PATCHED protein, and no RT genotype-phenotype correlations are evident."; RL Am. J. Hum. Genet. 60:21-26(1997). RN [7] RP VARIANT NBCCS ASP-1438. RX MEDLINE=98001068; PubMed=9341860; DOI=10.1007/s004390050541; RA Lench N.J., Telford E.A.R., High A.S., Markham A.F., Wicking C., RA Wainwright B.J.; RT "Characterisation of human patched germ line mutations in naevoid RT basal cell carcinoma syndrome."; RL Hum. Genet. 100:497-502(1997). RN [8] RP VARIANT PRO-1315. RX MEDLINE=99211211; PubMed=10200051; RX DOI=10.1002/(SICI)1098-1004(1998)11:6<480::AID-HUMU9>3.3.CO;2-W; RA Hasenpusch-Theil K., Bataille V., Laehdetie J., Obermayr F., RA Sampson J.R., Frischauf A.-M.; RT "Gorlin syndrome: identification of 4 novel germ-line mutations of the RT human patched (PTCH) gene."; RL Hum. Mutat. 11:480-480(1998). RN [9] RP VARIANTS BCNS SER-376 AND VAL-1083 INS, AND VARIANT BCC TRP-1114. RX MEDLINE=98281604; PubMed=9620294; RX DOI=10.1046/j.1523-1747.1998.00222.x; RA Aszterbaum M., Rothman A.L., Johnson R.L., Fisher M., Xie J., RA Bonifas J.M., Zhang X., Scott M.P., Epstein E.H. Jr.; RT "Identification of mutations in the human PATCHED gene in sporadic RT basal cell carcinomas and in patients with the basal cell nevus RT syndrome."; RL J. Invest. Dermatol. 110:885-888(1998). RN [10] RP VARIANT PRO-1315. RX MEDLINE=20334946; PubMed=10874314; RX DOI=10.1002/1098-1004(200007)16:1<89::AID-HUMU18>3.3.CO;2-Z; RA Dong J., Gailani M.R., Pomeroy S.L., Reardon D., Bale A.E.; RT "Identification of PATCHED mutations in medulloblastomas by direct RT sequencing."; RL Hum. Mutat. 16:89-90(2000). RN [11] RP VARIANT BCNS PRO-1132. RX MEDLINE=21154106; PubMed=11231326; RX DOI=10.1046/j.1523-1747.2001.01279-2.x; RA Reifenberger J., Arnold N., Kiechle M., Reifenberger G., Hauschild A.; RT "Coincident PTCH and BRCA1 germline mutations in a patient with nevoid RT basal cell carcinoma syndrome and familial breast cancer."; RL J. Invest. Dermatol. 116:472-474(2001). RN [12] RP VARIANTS SQUAMOUS CELL CARCINOMA MET-829 AND LYS-1242. RX MEDLINE=21184537; PubMed=11286632; RX DOI=10.1046/j.1523-1747.2001.01301.x; RA Ping X.L., Ratner D., Zhang H., Wu X.L., Zhang M.J., Chen F.F., RA Silvers D.N., Peacocke M., Tsou H.C.; RT "PTCH mutations in squamous cell carcinoma of the skin."; RL J. Invest. Dermatol. 116:614-616(2001). RN [13] RP VARIANTS BCNS PRO-230 AND 505-LEU-ARG-506. RX PubMed=15459969; DOI=10.1002/humu.9289; RA Savino M., d'Apolito M., Formica V., Baorda F., Mari F., Renieri A., RA Carabba E., Tarantino E., Andreucci E., Belli S., Lo Muzio L., RA Dallapiccola B., Zelante L., Savoia A.; RT "Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma RT syndrome patients: identification of thirteen novel alleles."; RL Hum. Mutat. 24:441-441(2004). CC -!- FUNCTION: Acts as a receptor for sonic hedgehog (SHH), indian CC hedgehog (IHH) and desert hedgehog (DHH). Associates with the CC smoothened protein (SMO) to transduce the hedgehog's proteins CC signal. Seems to have a tumor suppressor function, as inactivation CC of this protein is probably a necessary, if not sufficient step CC for tumorigenesis. CC -!- SUBUNIT: Interacts with SNX17. CC -!- SUBCELLULAR LOCATION: Membrane; multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: In the adult, expressed in brain, lung, liver, CC heart, placenta, skeletal muscle, pancreas and kidney. Expressed CC in tumor cells but not in normal skin. CC -!- DEVELOPMENTAL STAGE: In the embryo, found in all major target CC tissues of sonic hedgehog, such as the ventral neural tube, CC somites, and tissues surrounding the zone of polarizing activity CC of the limb bud. CC -!- PTM: Glycosylation is necessary for SHH binding (By similarity). CC -!- DISEASE: Defects in PTCH1 are probably the cause of basal cell CC nevus syndrome (BCNS) [MIM:109400]; also known as Gorlin syndrome CC or Gorlin-Goltz syndrome. BCNS is an autosomal dominant disease CC characterized by nevoid basal cell carcinomas (NBCCS) and CC developmental abnormalities such as rib and craniofacial CC alterations, polydactyly, syndactyly, and spina bifida. In CC addition, the patients suffer from a multitude of tumors like CC basal cell carcinomas (BCC), fibromas of the ovaries and heart, CC cysts of the skin, jaws and mesentery, as well as medulloblastomas CC and meningiomas. PTCH1 is also mutated in squamous cell carcinoma CC (SCC). Could also be associated with large body size observed in CC BCNS patients. CC -!- DISEASE: Defects in PTCH1 are a cause of sporadic basal cell CC carcinoma (BCC) [MIM:605462]. CC -!- SIMILARITY: Belongs to the patched family. CC -!- SIMILARITY: Contains 1 SSD (sterol-sensing) domain. CC -!- WEB RESOURCE: NAME=PTCH1 mutation database; CC URL="http://www.cybergene.se/PTCH/ptchbase.html". CC -!- WEB RESOURCE: NAME=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PTCH100.html". CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=PTCH1". CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U59464; AAC50550.1; -; mRNA. DR EMBL; AL161729; CAH73817.1; -; Genomic_DNA. DR EMBL; U43148; AAC50496.1; -; mRNA. DR UniGene; Hs.494538; -. DR Ensembl; ENSG00000185920; Homo sapiens. DR KEGG; hsa:5727; -. DR HGNC; HGNC:9585; PTCH1. DR MIM; 109400; phenotype. DR MIM; 601309; gene+phenotype. DR MIM; 605462; phenotype. DR LinkHub; Q13635; -. DR ArrayExpress; Q13635; -. DR GermOnline; ENSG00000185920; Homo sapiens. DR RZPD-ProtExp; E1069; -. DR RZPD-ProtExp; IOH26295; -. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; ISS:UniProtKB. DR GO; GO:0004872; F:receptor activity; TAS:ProtInc. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0009953; P:dorsal/ventral pattern formation; ISS:UniProtKB. DR GO; GO:0030326; P:embryonic limb morphogenesis; ISS:UniProtKB. DR GO; GO:0040015; P:negative regulation of body size; ISS:UniProtKB. DR GO; GO:0009887; P:organ morphogenesis; ISS:UniProtKB. DR GO; GO:0016485; P:protein processing; ISS:UniProtKB. DR GO; GO:0043109; P:regulation of smoothened activity; ISS:UniProtKB. DR InterPro; IPR003392; Patched. DR InterPro; IPR004766; Patched_TM_rcpt. DR InterPro; IPR000731; SSD_5TM. DR Pfam; PF02460; Patched; 1. DR TIGRFAMs; TIGR00918; 2A060602; 1. DR PROSITE; PS50156; SSD; 1. KW Anti-oncogene; Cell cycle; Disease mutation; Glycoprotein; Membrane; KW Polymorphism; Receptor; Transmembrane. FT CHAIN 1 1447 Protein patched homolog 1. FT /FTId=PRO_0000205964. FT TOPO_DOM 1 100 Cytoplasmic (Potential). FT TRANSMEM 101 121 Potential. FT TOPO_DOM 122 436 Extracellular (Potential). FT TRANSMEM 437 457 Potential. FT TOPO_DOM 458 472 Cytoplasmic (Potential). FT TRANSMEM 473 493 Potential. FT TOPO_DOM 494 501 Extracellular (Potential). FT TRANSMEM 502 522 Potential. FT TOPO_DOM 523 547 Cytoplasmic (Potential). FT TRANSMEM 548 568 Potential. FT TOPO_DOM 569 577 Extracellular (Potential). FT TRANSMEM 578 598 Potential. FT TOPO_DOM 599 748 Cytoplasmic (Potential). FT TRANSMEM 749 769 Potential. FT TOPO_DOM 770 1027 Extracellular (Potential). FT TRANSMEM 1028 1048 Potential. FT TOPO_DOM 1049 1055 Cytoplasmic (Potential). FT TRANSMEM 1056 1076 Potential. FT TOPO_DOM 1077 1083 Extracellular (Potential). FT TRANSMEM 1084 1104 Potential. FT TOPO_DOM 1105 1121 Cytoplasmic (Potential). FT TRANSMEM 1122 1141 Potential. FT TOPO_DOM 1142 1154 Extracellular (Potential). FT TRANSMEM 1155 1175 Potential. FT TOPO_DOM 1176 1447 Cytoplasmic (Potential). FT DOMAIN 438 598 SSD. FT COMPBIAS 14 31 Gly-rich. FT CARBOHYD 141 141 N-linked (GlcNAc...) (Potential). FT CARBOHYD 312 312 N-linked (GlcNAc...) (Potential). FT CARBOHYD 349 349 N-linked (GlcNAc...) (Potential). FT CARBOHYD 414 414 N-linked (GlcNAc...) (Potential). FT CARBOHYD 875 875 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1000 1000 N-linked (GlcNAc...) (Potential). FT VARIANT 175 175 L -> P (in BCNS; sporadic BCC). FT /FTId=VAR_007843. FT VARIANT 230 230 T -> P (in BCNS). FT /FTId=VAR_020845. FT VARIANT 376 376 F -> S (in BCNS). FT /FTId=VAR_007844. FT VARIANT 505 506 FL -> LR (in BCNS). FT /FTId=VAR_020846. FT VARIANT 509 509 G -> R (in BCNS; could be a rare FT polymorphism). FT /FTId=VAR_010974. FT VARIANT 509 509 G -> V (in BCNS). FT /FTId=VAR_010975. FT VARIANT 513 513 D -> Y (in BCNS). FT /FTId=VAR_010976. FT VARIANT 815 815 I -> IPNI (in BCNS). FT /FTId=VAR_007845. FT VARIANT 816 816 Missing (in BCNS). FT /FTId=VAR_010977. FT VARIANT 829 829 V -> M (in squamous cell carcinoma). FT /FTId=VAR_010978. FT VARIANT 1069 1069 G -> R (in BCNS). FT /FTId=VAR_010979. FT VARIANT 1083 1083 V -> VV (in BCNS). FT /FTId=VAR_007846. FT VARIANT 1114 1114 R -> W (in BCNS and BCC). FT /FTId=VAR_007847. FT VARIANT 1132 1132 S -> P (in BCNS). FT /FTId=VAR_010980. FT VARIANT 1132 1132 S -> Y (in BCNS). FT /FTId=VAR_010981. FT VARIANT 1195 1195 T -> S (in dbSNP:rs2236405). FT /FTId=VAR_020440. FT VARIANT 1242 1242 E -> K (in squamous cell carcinoma). FT /FTId=VAR_010982. FT VARIANT 1282 1282 P -> L (in dbSNP:rs16909873). FT /FTId=VAR_020847. FT VARIANT 1315 1315 L -> P (in dbSNP:rs357564). FT /FTId=VAR_010983. FT VARIANT 1438 1438 E -> D (in BCNS; sporadic NBCCS). FT /FTId=VAR_010984. FT CONFLICT 1109 1109 G -> S (in Ref. 2). FT CONFLICT 1144 1144 E -> D (in Ref. 2). FT CONFLICT 1175 1175 L -> W (in Ref. 2). FT CONFLICT 1283 1283 R -> K (in Ref. 2). FT CONFLICT 1309 1309 E -> K (in Ref. 2). FT CONFLICT 1353 1353 A -> T (in Ref. 2). SQ SEQUENCE 1447 AA; 160561 MW; F293692BB7AD3FC5 CRC64; MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFKL GCYIQKNCGK FLVVGLLIFG AFAVGLKAAN LETNVEELWV EVGGRVSREL NYTRQKIGEE AMFNPQLMIQ TPKEEGANVL TTEALLQHLD SALQASRVHV YMYNRQWKLE HLCYKSGELI TETGYMDQII EYLYPCLIIT PLDCFWEGAK LQSGTAYLLG KPPLRWTNFD PLEFLEELKK INYQVDSWEE MLNKAEVGHG YMDRPCLNPA DPDCPATAPN KNSTKPLDMA LVLNGGCHGL SRKYMHWQEE LIVGGTVKNS TGKLVSAHAL QTMFQLMTPK QMYEHFKGYE YVSHINWNED KAAAILEAWQ RTYVEVVHQS VAQNSTQKVL SFTTTTLDDI LKSFSDVSVI RVASGYLLML AYACLTMLRW DCSKSQGAVG LAGVLLVALS VAAGLGLCSL IGISFNAATT QVLPFLALGV GVDDVFLLAH AFSETGQNKR IPFEDRTGEC LKRTGASVAL TSISNVTAFF MAALIPIPAL RAFSLQAAVV VVFNFAMVLL IFPAILSMDL YRREDRRLDI FCCFTSPCVS RVIQVEPQAY TDTHDNTRYS PPPPYSSHSF AHETQITMQS TVQLRTEYDP HTHVYYTTAE PRSEISVQPV TVTQDTLSCQ SPESTSSTRD LLSQFSDSSL HCLEPPCTKW TLSSFAEKHY APFLLKPKAK VVVIFLFLGL LGVSLYGTTR VRDGLDLTDI VPRETREYDF IAAQFKYFSF YNMYIVTQKA DYPNIQHLLY DLHRSFSNVK YVMLEENKQL PKMWLHYFRD WLQGLQDAFD SDWETGKIMP NNYKNGSDDG VLAYKLLVQT GSRDKPIDIS QLTKQRLVDA DGIINPSAFY IYLTAWVSND PVAYAASQAN IRPHRPEWVH DKADYMPETR LRIPAAEPIE YAQFPFYLNG LRDTSDFVEA IEKVRTICSN YTSLGLSSYP NGYPFLFWEQ YIGLRHWLLL FISVVLACTF LVCAVFLLNP WTAGIIVMVL ALMTVELFGM MGLIGIKLSA VPVVILIASV GIGVEFTVHV ALAFLTAIGD KNRRAVLALE HMFAPVLDGA VSTLLGVLML AGSEFDFIVR YFFAVLAILT ILGVLNGLVL LPVLLSFFGP YPEVSPANGL NRLPTPSPEP PPSVVRFAMP PGHTHSGSDS SDSEYSSQTT VSGLSEELRH YEAQQGAGGP AHQVIVEATE NPVFAHSTVV HPESRHHPPS NPRQQPHLDS GSLPPGRQGQ QPRRDPPREG LWPPLYRPRR DAFEISTEGH SGPSNRARWG PRGARSHNPR NPASTAMGSS VPGYCQPITT VTASASVTVA VHPPPVPGPG RNPRGGLCPG YPETDHGLFE DPHVPFHVRC ERRDSKVEVI ELQDVECEER PRGSSSN //