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2.A.6.6.13
Patched, PTCH1 or PTCH, of 1447 aas and 12 TMSs.  RND transporter-like receptor, regulates the activity of Smoothened of 7 TMSs via the Hedgehog (HH) pathway. The Na+ gradient may provide the energy for Patched activity (Myers et al. 2017). Possibly Patched1, chemiosmotically driven by the transmembrane Na+ gradient, regulates Smoothened. 3-d structures have been solved at ~ 3.5 Å resolution by cryoEM (Qi et al. 2018). This protein seems to have both transport and signalling functions, exporting cholesterol from the inner leaflet of the membrane out to the external environment. It displays a tunnel going through the membrane with a lateral opening, all large enough to accomodate cholesterol (Qi et al. 2018; Sommer and Lemmon 2018). The distrutribution of Smoothened on the primary cillium surface has been studied (Yoon et al. 2019).
Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched that suppresses the activity of the 7-TMS protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of Patched revealed striking transmembrane domain similarities to prokaryotic RND transporters in whick a central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting that Patched catalyzes cholesterol transport (Zhang et al. 2018). Cholesterol in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability.
Key proteins in the Hedgehog-signalling pathway dynamically localize in primary cilia, antenna-like solitary organelles present on most cells. The secreted Hedgehog ligand Sonic Hedgehog (SHH) binds to its receptor Patched1 (PTCH1) in primary cilia, causing its inactivation and delocalization from cilia. At the same time, the transmembrane protein Smoothened (SMO or SMOH; TC# 9.A.14.16.4) is released of its inhibition by PTCH1 and accumulates in cilia. PTCH1 inactivation by SHH changes the diffusive motion of PTCH1 (Weiss et al. 2019).

Accession Number:Q13635
Protein Name:Protein patched homolog 1
Length:1447
Molecular Weight:160545.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

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FASTA formatted sequence
1:	MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF 
61:	ALEQISKGKA TGRKAPLWLR AKFQRLLFKL GCYIQKNCGK FLVVGLLIFG AFAVGLKAAN 
121:	LETNVEELWV EVGGRVSREL NYTRQKIGEE AMFNPQLMIQ TPKEEGANVL TTEALLQHLD 
181:	SALQASRVHV YMYNRQWKLE HLCYKSGELI TETGYMDQII EYLYPCLIIT PLDCFWEGAK 
241:	LQSGTAYLLG KPPLRWTNFD PLEFLEELKK INYQVDSWEE MLNKAEVGHG YMDRPCLNPA 
301:	DPDCPATAPN KNSTKPLDMA LVLNGGCHGL SRKYMHWQEE LIVGGTVKNS TGKLVSAHAL 
361:	QTMFQLMTPK QMYEHFKGYE YVSHINWNED KAAAILEAWQ RTYVEVVHQS VAQNSTQKVL 
421:	SFTTTTLDDI LKSFSDVSVI RVASGYLLML AYACLTMLRW DCSKSQGAVG LAGVLLVALS 
481:	VAAGLGLCSL IGISFNAATT QVLPFLALGV GVDDVFLLAH AFSETGQNKR IPFEDRTGEC 
541:	LKRTGASVAL TSISNVTAFF MAALIPIPAL RAFSLQAAVV VVFNFAMVLL IFPAILSMDL 
601:	YRREDRRLDI FCCFTSPCVS RVIQVEPQAY TDTHDNTRYS PPPPYSSHSF AHETQITMQS 
661:	TVQLRTEYDP HTHVYYTTAE PRSEISVQPV TVTQDTLSCQ SPESTSSTRD LLSQFSDSSL 
721:	HCLEPPCTKW TLSSFAEKHY APFLLKPKAK VVVIFLFLGL LGVSLYGTTR VRDGLDLTDI 
781:	VPRETREYDF IAAQFKYFSF YNMYIVTQKA DYPNIQHLLY DLHRSFSNVK YVMLEENKQL 
841:	PKMWLHYFRD WLQGLQDAFD SDWETGKIMP NNYKNGSDDG VLAYKLLVQT GSRDKPIDIS 
901:	QLTKQRLVDA DGIINPSAFY IYLTAWVSND PVAYAASQAN IRPHRPEWVH DKADYMPETR 
961:	LRIPAAEPIE YAQFPFYLNG LRDTSDFVEA IEKVRTICSN YTSLGLSSYP NGYPFLFWEQ 
1021:	YIGLRHWLLL FISVVLACTF LVCAVFLLNP WTAGIIVMVL ALMTVELFGM MGLIGIKLSA 
1081:	VPVVILIASV GIGVEFTVHV ALAFLTAIGD KNRRAVLALE HMFAPVLDGA VSTLLGVLML 
1141:	AGSEFDFIVR YFFAVLAILT ILGVLNGLVL LPVLLSFFGP YPEVSPANGL NRLPTPSPEP 
1201:	PPSVVRFAMP PGHTHSGSDS SDSEYSSQTT VSGLSEELRH YEAQQGAGGP AHQVIVEATE 
1261:	NPVFAHSTVV HPESRHHPPS NPRQQPHLDS GSLPPGRQGQ QPRRDPPREG LWPPPYRPRR 
1321:	DAFEISTEGH SGPSNRARWG PRGARSHNPR NPASTAMGSS VPGYCQPITT VTASASVTVA 
1381:	VHPPPVPGPG RNPRGGLCPG YPETDHGLFE DPHVPFHVRC ERRDSKVEVI ELQDVECEER 
1441:	PRGSSSN