ID Q13635 PRELIMINARY; PRT; 1447 AA. AC Q13635; Q13463; DT 01-NOV-1996 (TrEMBLrel. 01, Created) DT 01-NOV-1996 (TrEMBLrel. 01, Last sequence update) DT 01-MAY-1999 (TrEMBLrel. 10, Last annotation update) DE PATCHED PROTEIN HOMOLOG (PTC). GN PTCH OR NBCCS. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Mammalia; OC Eutheria; Primates; Catarrhini; Hominidae; Homo. RN [1] RP SEQUENCE FROM N.A., AND VARIANTS BCC 175-PRO AND 815-PRO-ASN-ILE INS. RC TISSUE=LUNG; RX MEDLINE; 96247324. 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 SEQUENCE OF 152-1447 FROM N.A. RC TISSUE=FETAL BRAIN; RX MEDLINE; 96218118. 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.; 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 [3] RP VARIANTS BCNS 376-SER; BCNS 1083-VAL INS AND BCC 1114-TRP. RX MEDLINE; 98281604. RA ASZTERBAUM M., ROTHMAN A., 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). CC -!- FUNCTION: ACTS AS A RECEPTOR FOR THE SONIC HEDGEHOG (SHH), THE CC INDIAN HEDGEHOG (IHH), AND THE DESERT HEDGEHOG (DHH) PROTEINS. CC ASSOCIATES WITH THE SMOOTHENED PROTEIN (SMO) TO TRANSDUCE THE CC HEDGEHOG'S PROTEINS SIGNAL. SEEMS TO HAVE A TUMOR SUPPRESSOR CC FUNCTION, AS INACTIVATION OF THIS PROTEIN IS PROBABLY A NECESSARY, CC IF NOT SUFFICIENT STEP FOR TUMORIGENESIS. CC -!- SUBCELLULAR LOCATION: INTEGRAL MEMBRANE PROTEIN. 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 -!- 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 -!- PTM: GLYCOSYLATION IS NECESSARY FOR SHH BINDING (BY SIMILARITY). CC -!- DISEASE: DEFECTS IN PTC ARE PROBABLY THE CAUSE OF BASAL CELL NEVUS CC SYNDROME (BCNS, ALSO CALLED GORLIN SYNDROME OR GORLIN-GOLTZ CC SYNDROME), AN AUTOSOMAL DOMINANT DISEASE CHARACTERIZED BY NEVOID CC BASAL CELL CARCINOMAS (NBCCS) AND DEVELOPMENTAL ABNORMALITIES SUCH CC AS RIB AND CRANIOFACIAL ALTERATIONS, POLYDACTYLY, SYNDACTYLY, AND CC SPINA BIFIDA. IN ADDITION, THE PATIENTS SUFFER FROM A MULTITUDE OF CC TUMORS LIKE BASAL CELL CARCINOMAS (BCC), FIBROMAS OF THE OVARIES CC AND HEART, CYSTS OF THE SKIN, JAWS AND MESENTERY, AS WELL AS CC MEDULLOBLASTOMAS AND MENINGIOMAS. PTC COULD ALSO BE ASSOCIATED CC WITH LARGE BODY SIZE OBSERVED IN BCNS PATIENTS. CC -!- SIMILARITY: BELONGS TO PATCHED FAMILY. 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; -. DR EMBL; U43148; AAC50496.1; -. DR MIM; 601309; -. DR MIM; 109400; -. KW Disease mutation; Transmembrane; Glycoprotein; Developmental protein; KW Receptor. FT DOMAIN 1 100 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 101 121 POTENTIAL. FT DOMAIN 122 436 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 437 457 POTENTIAL. FT DOMAIN 458 472 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 473 493 POTENTIAL. FT DOMAIN 494 501 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 502 522 POTENTIAL. FT DOMAIN 523 547 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 548 568 POTENTIAL. FT DOMAIN 569 577 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 578 598 POTENTIAL. FT DOMAIN 599 748 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 749 769 POTENTIAL. FT DOMAIN 770 1027 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 1028 1048 POTENTIAL. FT DOMAIN 1049 1055 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 1056 1076 POTENTIAL. FT DOMAIN 1077 1083 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 1084 1104 POTENTIAL. FT DOMAIN 1105 1121 CYTOPLASMIC (POTENTIAL). FT TRANSMEM 1122 1141 POTENTIAL. FT DOMAIN 1142 1154 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 1155 1175 POTENTIAL. FT DOMAIN 1176 1447 CYTOPLASMIC (POTENTIAL). FT DOMAIN 14 19 POLY-GLY. FT DOMAIN 32 35 POLY-ARG. FT DOMAIN 423 426 POLY-THR. FT DOMAIN 579 582 POLY-VAL. FT DOMAIN 641 644 POLY-PRO. FT VARIANT 175 175 L -> P (IN SPORADIC BCC). FT VARIANT 376 376 F -> S (IN BCNS). FT VARIANT 815 815 I -> IPNI (IN BCNS). FT VARIANT 1083 1083 V -> VV (IN BCNS). FT VARIANT 1114 1114 R -> W (IN SPORADIC BCC). FT CARBOHYD 141 141 POTENTIAL. FT CARBOHYD 312 312 POTENTIAL. FT CARBOHYD 349 349 POTENTIAL. FT CARBOHYD 414 414 POTENTIAL. FT CARBOHYD 875 875 POTENTIAL. FT CARBOHYD 1000 1000 POTENTIAL. 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; 160560 MW; 6BD592C2 CRC32; 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 //