ID FZD6_HUMAN Reviewed; 706 AA. AC O60353; B4DRN0; Q6N0A5; Q6P9C3; Q8WXR9; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 204. DE RecName: Full=Frizzled-6; DE Short=Fz-6; DE Short=hFz6; DE Flags: Precursor; GN Name=FZD6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-345. RC TISSUE=Fetal lung; RX PubMed=9480858; DOI=10.1006/bbrc.1998.8143; RA Tokuhara M., Hirai M., Atomi Y., Terada M., Katoh M.; RT "Molecular cloning of human frizzled-6."; RL Biochem. Biophys. Res. Commun. 243:622-627(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-345. RA Gazit A., Yaniv A., Aaronson S.A.; RT "Molecular cloning of the human Frizzled 6."; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11707601; DOI=10.1073/pnas.241525498; RA Tanner S.M., Austin J.L., Leone G., Rush L.J., Plass C., Heinonen K., RA Mrozek K., Sill H., Knuutila S., Kolitz J.E., Archer K.J., Caligiuri M.A., RA Bloomfield C.D., de La Chapelle A.; RT "BAALC, the human member of a novel mammalian neuroectoderm gene lineage, RT is implicated in hematopoiesis and acute leukemia."; RL Proc. Natl. Acad. Sci. U.S.A. 98:13901-13906(2001). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.; RT "Genome-wide discovery and analysis of human seven transmembrane helix RT receptor genes."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-33. RC TISSUE=Uterine endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-345. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP POSSIBLE INVOLVEMENT IN NEURAL TUBE DEFECTS, AND VARIANTS VAL-33; TYR-140; RP GLU-152; LEU-345; ASP-388; GLN-405; CYS-511; HIS-511; ARG-604; THR-620 AND RP GLU-664. RX PubMed=22045688; DOI=10.1002/humu.21643; RA De Marco P., Merello E., Rossi A., Piatelli G., Cama A., Kibar Z., RA Capra V.; RT "FZD6 is a novel gene for human neural tube defects."; RL Hum. Mutat. 33:384-390(2012). RN [12] RP UBIQUITINATION BY ZNRF3. RX PubMed=22575959; DOI=10.1038/nature11019; RA Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., RA Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., RA Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.; RT "ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner."; RL Nature 485:195-200(2012). RN [13] RP VARIANT NDNC1 CYS-511, AND CHARACTERIZATION OF VARIANT NDNC1 CYS-511. RX PubMed=21665003; DOI=10.1016/j.ajhg.2011.05.013; RA Frojmark A.S., Schuster J., Sobol M., Entesarian M., Kilander M.B., RA Gabrikova D., Nawaz S., Baig S.M., Schulte G., Klar J., Dahl N.; RT "Mutations in Frizzled 6 cause isolated autosomal-recessive nail RT dysplasia."; RL Am. J. Hum. Genet. 88:852-860(2011). CC -!- FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are CC coupled to the beta-catenin canonical signaling pathway, which leads to CC the activation of disheveled proteins, inhibition of GSK-3 kinase, CC nuclear accumulation of beta-catenin and activation of Wnt target CC genes. A second signaling pathway involving PKC and calcium fluxes has CC been seen for some family members, but it is not yet clear if it CC represents a distinct pathway or if it can be integrated in the CC canonical pathway, as PKC seems to be required for Wnt-mediated CC inactivation of GSK-3 kinase. Both pathways seem to involve CC interactions with G-proteins. May be involved in transduction and CC intercellular transmission of polarity information during tissue CC morphogenesis and/or in differentiated tissues. Together with FZD3, is CC involved in the neural tube closure and plays a role in the regulation CC of the establishment of planar cell polarity (PCP), particularly in the CC orientation of asymmetric bundles of stereocilia on the apical faces of CC a subset of auditory and vestibular sensory cells located in the inner CC ear (By similarity). {ECO:0000250|UniProtKB:Q61089}. CC -!- SUBUNIT: Interacts with LMBR1L. {ECO:0000250|UniProtKB:Q61089}. CC -!- INTERACTION: CC O60353; P47972: NPTX2; NbExp=9; IntAct=EBI-8754490, EBI-3957229; CC O60353; Q8N474: SFRP1; NbExp=3; IntAct=EBI-8754490, EBI-3940687; CC O60353; Q9ULT6: ZNRF3; NbExp=2; IntAct=EBI-8754490, EBI-949772; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q61089}; Multi- CC pass membrane protein {ECO:0000255}. Cell membrane CC {ECO:0000250|UniProtKB:Q61089}; Multi-pass membrane protein CC {ECO:0000255}. Cell surface {ECO:0000250|UniProtKB:Q61089}. Apical cell CC membrane; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic CC vesicle membrane {ECO:0000250|UniProtKB:Q61089}; Multi-pass membrane CC protein {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q61089}; Multi-pass membrane protein CC {ECO:0000255}. Note=Colocalizes with FZD3 at the apical face of cells CC (By similarity). Localizes to the endoplasmic reticulum membrane in the CC presence of LMBR1L (By similarity). {ECO:0000250|UniProtKB:Q61089}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60353-1; Sequence=Displayed; CC Name=2; CC IsoId=O60353-2; Sequence=VSP_044291; CC -!- TISSUE SPECIFICITY: Detected in adult heart, brain, placenta, lung, CC liver, skeletal muscle, kidney, pancreas, thymus, prostate, testis, CC ovary, small intestine and colon. In the fetus, expressed in brain, CC lung, liver and kidney. CC -!- DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl CC (Disheveled) family members and is involved in the activation of the CC Wnt/beta-catenin signaling pathway. {ECO:0000250}. CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands. CC {ECO:0000250}. CC -!- PTM: Ubiquitinated by ZNRF3, leading to its degradation by the CC proteasome. {ECO:0000250}. CC -!- DISEASE: Nail disorder, non-syndromic congenital, 1 (NDNC1) CC [MIM:161050]: An autosomal recessive nail disorder characterized by a CC variable degree of onychauxis (thick nails), hyponychia, and CC onycholysis of all nails, with claw-shaped fingernails in some CC individuals. No other anomalies of ectodermal tissues, including hair, CC teeth, sweat glands, or skin, are noted, and individuals with CC dysplastic nails have normal hearing and normal psychomotor CC development. {ECO:0000269|PubMed:21665003}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Note=Rare non-synonymous variants in FZD6 may contribute to CC neural tube defects, congenital malformations of the central nervous CC system and adjacent structures related to defective neural tube closure CC during the first trimester of pregnancy. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family. CC {ECO:0000305}. 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; AB012911; BAA25686.1; -; mRNA. DR EMBL; AF072873; AAD41637.1; -; mRNA. DR EMBL; AF363578; AAL50384.1; -; Genomic_DNA. DR EMBL; AB065702; BAC05925.1; -; Genomic_DNA. DR EMBL; AK299341; BAG61342.1; -; mRNA. DR EMBL; BX640609; CAE45715.1; -; mRNA. DR EMBL; AC025370; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW91867.1; -; Genomic_DNA. DR EMBL; BC060836; AAH60836.2; -; mRNA. DR CCDS; CCDS55268.1; -. [O60353-2] DR CCDS; CCDS6298.1; -. [O60353-1] DR PIR; JE0164; JE0164. DR RefSeq; NP_001158087.1; NM_001164615.1. [O60353-1] DR RefSeq; NP_001158088.1; NM_001164616.1. [O60353-2] DR RefSeq; NP_001304725.1; NM_001317796.1. DR RefSeq; NP_003497.2; NM_003506.3. [O60353-1] DR AlphaFoldDB; O60353; -. DR SMR; O60353; -. DR BioGRID; 113919; 91. DR DIP; DIP-59893N; -. DR IntAct; O60353; 19. DR MINT; O60353; -. DR STRING; 9606.ENSP00000351605; -. DR GuidetoPHARMACOLOGY; 234; -. DR CarbonylDB; O60353; -. DR GlyConnect; 2042; 2 N-Linked glycans (1 site). DR GlyCosmos; O60353; 4 sites, 5 glycans. DR GlyGen; O60353; 6 sites, 4 N-linked glycans (1 site), 2 O-linked glycans (4 sites). DR iPTMnet; O60353; -. DR PhosphoSitePlus; O60353; -. DR SwissPalm; O60353; -. DR BioMuta; FZD6; -. DR EPD; O60353; -. DR jPOST; O60353; -. DR MassIVE; O60353; -. DR MaxQB; O60353; -. DR PaxDb; 9606-ENSP00000351605; -. DR PeptideAtlas; O60353; -. DR ProteomicsDB; 49378; -. [O60353-1] DR ProteomicsDB; 4963; -. DR Antibodypedia; 2906; 373 antibodies from 37 providers. DR DNASU; 8323; -. DR Ensembl; ENST00000358755.5; ENSP00000351605.4; ENSG00000164930.12. [O60353-1] DR Ensembl; ENST00000522566.5; ENSP00000429055.1; ENSG00000164930.12. [O60353-1] DR Ensembl; ENST00000523739.5; ENSP00000429528.1; ENSG00000164930.12. [O60353-2] DR GeneID; 8323; -. DR KEGG; hsa:8323; -. DR MANE-Select; ENST00000358755.5; ENSP00000351605.4; NM_003506.4; NP_003497.2. DR UCSC; uc003ylh.4; human. [O60353-1] DR AGR; HGNC:4044; -. DR CTD; 8323; -. DR DisGeNET; 8323; -. DR GeneCards; FZD6; -. DR HGNC; HGNC:4044; FZD6. DR HPA; ENSG00000164930; Low tissue specificity. DR MalaCards; FZD6; -. DR MIM; 161050; phenotype. DR MIM; 603409; gene. DR neXtProt; NX_O60353; -. DR OpenTargets; ENSG00000164930; -. DR Orphanet; 280654; Autosomal recessive nail dysplasia. DR PharmGKB; PA28461; -. DR VEuPathDB; HostDB:ENSG00000164930; -. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000158485; -. DR HOGENOM; CLU_007873_4_0_1; -. DR InParanoid; O60353; -. DR OMA; FLKHNNR; -. DR OrthoDB; 5483535at2759; -. DR PhylomeDB; O60353; -. DR TreeFam; TF317907; -. DR PathwayCommons; O60353; -. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR Reactome; R-HSA-4086398; Ca2+ pathway. DR Reactome; R-HSA-4086400; PCP/CE pathway. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants. DR SignaLink; O60353; -. DR SIGNOR; O60353; -. DR BioGRID-ORCS; 8323; 9 hits in 1157 CRISPR screens. DR ChiTaRS; FZD6; human. DR GeneWiki; FZD6; -. DR GenomeRNAi; 8323; -. DR Pharos; O60353; Tbio. DR PRO; PR:O60353; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; O60353; Protein. DR Bgee; ENSG00000164930; Expressed in bronchial epithelial cell and 176 other cell types or tissues. DR ExpressionAtlas; O60353; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0042813; F:Wnt receptor activity; IDA:BHF-UCL. DR GO; GO:0017147; F:Wnt-protein binding; ISS:BHF-UCL. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0033278; P:cell proliferation in midbrain; IEA:Ensembl. DR GO; GO:0035880; P:embryonic nail plate morphogenesis; IEA:Ensembl. DR GO; GO:0048105; P:establishment of body hair planar orientation; IEA:Ensembl. DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:1904693; P:midbrain morphogenesis; TAS:ParkinsonsUK-UCL. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0030168; P:platelet activation; IEA:Ensembl. DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; NAS:ParkinsonsUK-UCL. DR CDD; cd15032; 7tmF_FZD6; 1. DR CDD; cd07450; CRD_FZ6; 1. DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR015526; Frizzled/SFRP. DR InterPro; IPR000539; Frizzled/Smoothened_7TM. DR InterPro; IPR020067; Frizzled_dom. DR InterPro; IPR036790; Frizzled_dom_sf. DR InterPro; IPR041770; FZ6_CRD. DR InterPro; IPR026543; FZD6_7TM. DR InterPro; IPR017981; GPCR_2-like_7TM. DR PANTHER; PTHR11309; FRIZZLED; 1. DR PANTHER; PTHR11309:SF75; FRIZZLED-6; 1. DR Pfam; PF01534; Frizzled; 1. DR Pfam; PF01392; Fz; 1. DR PRINTS; PR00489; FRIZZLED. DR SMART; SM00063; FRI; 1. DR SMART; SM01330; Frizzled; 1. DR SUPFAM; SSF63501; Frizzled cysteine-rich domain; 1. DR PROSITE; PS50038; FZ; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR Genevisible; O60353; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; KW Developmental protein; Disease variant; Disulfide bond; KW Endoplasmic reticulum; G-protein coupled receptor; Glycoprotein; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix; Ubl conjugation; Wnt signaling pathway. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..706 FT /note="Frizzled-6" FT /id="PRO_0000012994" FT TOPO_DOM 19..201 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 202..222 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 223..233 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 234..254 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 255..284 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 285..305 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 306..324 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 325..345 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 346..370 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 371..391 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 392..416 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 417..437 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 438..473 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 474..494 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 495..706 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 19..132 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT REGION 588..706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 498..503 FT /note="Lys-Thr-X-X-X-Trp motif, mediates interaction with FT the PDZ domain of Dvl family members" FT /evidence="ECO:0000250" FT COMPBIAS 658..686 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 653 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61089" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 24..85 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 32..78 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 69..106 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 95..129 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 99..123 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT VAR_SEQ 1..32 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044291" FT VARIANT 33 FT /note="M -> V (in dbSNP:rs827528)" FT /evidence="ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:22045688" FT /id="VAR_047440" FT VARIANT 140 FT /note="H -> Y (in dbSNP:rs80216383)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066963" FT VARIANT 152 FT /note="Q -> E (in dbSNP:rs61753730)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066964" FT VARIANT 345 FT /note="M -> L (in dbSNP:rs3808553)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:22045688, ECO:0000269|PubMed:9480858, FT ECO:0000269|Ref.2" FT /id="VAR_047441" FT VARIANT 388 FT /note="A -> D (in dbSNP:rs142694816)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066965" FT VARIANT 405 FT /note="R -> Q (in dbSNP:rs150760762)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066966" FT VARIANT 511 FT /note="R -> C (in NDNC1; also found in a patient with FT neural tube defects; the mutant protein localizes to the FT lysosomes compared to wild-type; dbSNP:rs151339003)" FT /evidence="ECO:0000269|PubMed:21665003, FT ECO:0000269|PubMed:22045688" FT /id="VAR_066398" FT VARIANT 511 FT /note="R -> H (in a patient with neural tube defects; FT dbSNP:rs767273753)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066967" FT VARIANT 604 FT /note="G -> R (in dbSNP:rs79408516)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066968" FT VARIANT 620 FT /note="S -> T (in dbSNP:rs116195528)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_066969" FT VARIANT 664 FT /note="A -> E (in dbSNP:rs12549394)" FT /evidence="ECO:0000269|PubMed:22045688" FT /id="VAR_047442" SQ SEQUENCE 706 AA; 79292 MW; FBFF5844D6AB0223 CRC64; MEMFTFLLTC IFLPLLRGHS LFTCEPITVP RCMKMAYNMT FFPNLMGHYD QSIAAVEMEH FLPLANLECS PNIETFLCKA FVPTCIEQIH VVPPCRKLCE KVYSDCKKLI DTFGIRWPEE LECDRLQYCD ETVPVTFDPH TEFLGPQKKT EQVQRDIGFW CPRHLKTSGG QGYKFLGIDQ CAPPCPNMYF KSDELEFAKS FIGTVSIFCL CATLFTFLTF LIDVRRFRYP ERPIIYYSVC YSIVSLMYFI GFLLGDSTAC NKADEKLELG DTVVLGSQNK ACTVLFMLLY FFTMAGTVWW VILTITWFLA AGRKWSCEAI EQKAVWFHAV AWGTPGFLTV MLLAMNKVEG DNISGVCFVG LYDLDASRYF VLLPLCLCVF VGLSLLLAGI ISLNHVRQVI QHDGRNQEKL KKFMIRIGVF SGLYLVPLVT LLGCYVYEQV NRITWEITWV SDHCRQYHIP CPYQAKAKAR PELALFMIKY LMTLIVGISA VFWVGSKKTC TEWAGFFKRN RKRDPISESR RVLQESCEFF LKHNSKVKHK KKHYKPSSHK LKVISKSMGT STGATANHGT SAVAITSHDY LGQETLTEIQ TSPETSMREV KADGASTPRL REQDCGEPAS PAASISRLSG EQVDGKGQAG SVSESARSEG RISPKSDITD TGLAQSNNLQ VPSSSEPSSL KGSTSLLVHP VSGVRKEQGG GCHSDT //