IUPHAR Nomenclature Report: The Class Frizzled
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1 supplemental material IUPHAR Nomenclature Report: The Class Frizzled receptors Gunnar Schulte Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S Stockholm, Sweden
2 Figure S1: Protein sequence alignment of the Class Frizzled receptors FZD 1-10 and SMO. Alignment was performed with ClustalW2, a general purpose multiple sequence alignment program for DNA or proteins ( Bars indicate the location of the cystein rich domain (CRD) in the N terminal region and the seven transmembrane spanning domains (TM1-TM7).
3 Page 1 CRD Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
4 Page 2 TM1 Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
5 TM2 Page 3 TM3 TM4 TM5 Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
6 TM6 Page 4 TM7 KTxxxW Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
7 Page 5 Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
8 Figure S2: The intracellular domains of the Class Frizzled receptors (FZD 1-10 and SMO), i e the first, second and third intracellular loops and the C terminus were analyzed for putative phosphorylation sites (underlined) with the Mini Motif Miner software MnM2.0 (Balla et al, 2006). The conserved KTxxxW site in FZD 1-10 is marked with bold letters. The terminal PDZ ligand domains are marked in grey.
9 Intracellular domains of human FZDs underlined potential phosphorylation sites accoring to MiniMotifMiner grey Class I PDZ ligand sequence human FZD 1 : FZD DMRRFSYPERP-354 FZD SLTWFLAAGMKWGHEAIEANSQ-445 FZD VSLFRIRTIMKHDGTKTEKLEKLMVR-536 FZD SGKTLNSWRKFYTRLTNSKQGETTV-647 human FZD 2 : FZD DMQRFRYPERP-279 FZD SLTWFLAAGMKWGHEAIEANSQ-370 FZD VSLFRIRTIMKHDGTKTEKLERLMVR-461 FZD SGKTLHSWRKFYTRLTNSRHGETTV -565 human FZD 3 : FZD DVTRFRYPERP-237 FZD TWFLAAVPKWGSEAIEKKA-328 FZD SLNRVRIEIPLEKENQDKLVKFMIR-420 FZD GSKKTCFEWASFFHGRRKKEIVNESRQVL QEPDFAQSLLRDPNTPIIRKSRGTSTQGTSTHASSTQ LAMVDDQRSKAGSIHSKVSSYHGSLHRSRDGRYTPC SYRGMEERLPHGSMSRLTDHSRHSSSHRLNEQSR HSSIRDLSNNPMTHITHGTSMNRVIEEDGTSA-666 human FZD 4 : FZD DSSRFSYPERP-254 FZD TLTWFLAAGLKWGHEAIEMHS-344 FZD VALFKIRSNLQKDGTKTDKLERLMVK-436 FZD KTLHTWQKCSNRLVNSGKVKREKRGNGW VKPGKGSETVV -537 human FZD 5 : FZD DMERFRYPERP-270 FZD SLTWFLAAGMKWGNEAIAGYAQ-358 FZD VSLFRIRSVIKQGGTKTDKLEKLMIR-449 FZD WSGKTVESWRRFTSRCCCRPRRGHKSG GAMAAGDYPEASAALTGRTGPPGPAATYHKQVS LSHV-585 human FZD6: FZD6 223-DVRRFRYPERP-233 FZD6 306-TWFLAAGRKWSCEAIEQKA-324 FZD6 392-SLNHVRQVIQHDGRNQEKLKKFMIR-416 FZD6-465-GSKKTCTEWAGFFKRNRKRDPISESRRVLQ ESCEFFLKHNSKVKHKKKHYKPSSHKLKVISKSMGTST GATANHGTSAVAITSHDYLGQETLTEIQTSPETSMREV KADGASTPRLREQDCGEPASPAASISRLSGEQVDGKG QAGSVSESARSEGRISPKSDITDTGLAQSNNLQVPSSS EPSSLKGSTSLLVHPVSGVRKEQGGGCHSDT-706 human FZD 7 : FZD DMRRFSYPERP-288 FZD SLTWFLAAGMKWGHEAIEANSQ-379 FZD VSLFRIRTIMKHDGTKTEKLEKLMVR-470 FZD SGKTLQSWRRFYHRLSHSSKGETAV-574 human FZD 8 : FZD STFLIDMERFKYPERP-312 FZD SLTWFLAAGMKWGNEAIAGYSQY-439 FZD VSLFRIRSVIKQQDGPTKTHKLEKLMIR-532 FZD SGKTLESWRSLCTRCCWASKGAAVGGGAG ATAAGGGGGPGGGGGGGPGGGGGPGGGGGSLYSDV STGLTWRSGTASSVSYPKQMPLSQV-694 human FZD 9 : FZD LTFLLEPHRFQYPERP-366 FZD TWFLAAGKKWGHEAIEAHG-355 FZD VALFHIRKIMKTGGTNTEKLEKLMVK-447 FZD SSKTFQTWQSLCYRKIAAGRARAKACRAPG SYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL -591 human FZD 10 : FZD LTFLIDPARFRYPERP-262 FZD TWFLAAGKKWGHEAIEANS-351 FZD SGFVALFHIRRVMKTGGENTDKLEKLMVR-443 FZD TSKTLQSWQQVCSRRLKKKSRRKPASVITSGG IYKKAQHPQKTHHGKYEIPAQSPTCV-581 human SMO: SMO 255-DWRNSNRY-262 SMO 336-TYAWHTSFKALGTTYQPLSGKTS -358 SMO 424-MTLFSIKSNHPGLLSEKAASKINETMLR -451 SMO-546-RRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELL QNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQH VTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAEISPEL QKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLP RQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFL PSAPAPVAWAHGRRQGLGPIHSRTNLMDTELMDADSDF-787 Supplemental Material Class Frizzled receptor aligment Schulte, G. Pharmacological Reviews 2010
10 Figure S3: Summary of putative Class Frizzled receptor kinases and their suggested target regions in the receptors. Abbreviations: ABL, non-receptor protein tyrosine kinase derived from oncogene c-abl; ATM, Ataxia telangiectasia mutated kinase; CamKII, Ca 2+ /calmodulin-dependent kinase II; CDK, cyclindependent kinase; CK, casein kinase; CSK, EGFR, epidermal growth factor receptor; ERK1/2, extracellular signal-regulated kinases 1/2; GSK3, glycogen synthase kinase 3; JAK2, Janus kinase 2; p70s6 kinase, Ser/Thr knase 70 kda phosphorylating the ribosomal S6 protein; PLK, polo-like kinase; PKA, campdependent protein kinase; PKC, Ca 2+ -dependent protein kinase; PKG, cgmpdependent protein kinase; RSK, SRC, non-receptor protein tyrosine kinase derived from oncogene c-src;
11 P70 S6 kinase ERK1/2 ATM JAK2 GSK3α GSK3β PLK CDK Phosphorylase kinase ABL EGFR TPK- IIB/p38SYK CSK SRC FZD domain PKA PKC PKG CK1 CK2 CamKII RSK FZD 1 _i1 FZD 1 _i2 FZD 1 _i3 (x2) FZD 1 _c-term (x2) FZD 2 _i1 FZD 2 _i2 FZD 2 _i3 FZD 2 _c-term (x2) FZD 3 _i1 FZD 3 _i2 FZD 3 _i3 FZD 3 _c-term (x6) (x4) (x7) (x2) (x5) (x6) (x2) (x11) (x3) (x2) FZD 4 _i1 FZD 4 _i2 FZD 4 _i3 (x2) FZD 4 _c-term (x2) FZD 5 _i1 FZD 5 _i2 FZD 5 _i3 FZD 5 _c-term (x2) (x4) (x2) (x3) FZD 6 _i1 FZD 6 _i2 FZD 6 _i3 FZD 6 _c-term (x2) (x8) (x8) (x7) (x5) (x7) FZD 7 _i1 (x2) FZD 7 _i2 FZD 7 _i3 (x2) FZD 7 _c-term (x3) (x2) FZD 8 _i1 FZD 8 _i2 FZD 8 _i3 (x2) FZD 8 _c-term (x3) (x6) FZD 9 _i1 FZD 9 _i2 FZD 9 _i3 FZD 9 _c-term FZD 10 _i1 FZD 10 _i2 FZD 10 _i3 FZD 10 _cterm (x3) (x2) SMO_i1 SMO_i2 (x2) (x2) SMO_i3 (x2) SMO_c-term (x2) (x2) (x3) (x3) (x2)
12 References Balla S, Thapar V, Verma S, Luong T, Faghri T, Huang CH, Rajasekaran S, del Campo JJ, Shinn JH, Mohler WA, Maciejewski MW, Gryk MR, Piccirillo B, Schiller SR and Schiller MR (2006) Minimotif Miner: a tool for investigating protein function. Nat Methods 3(3):
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