FZD6_HUMAN
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 03-AUG-2022, entry version 195.
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}.
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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; 89.
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 GlyGen; O60353; 4 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (2 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; O60353; -.
DR PeptideAtlas; O60353; -.
DR PRIDE; O60353; -.
DR ProteomicsDB; 49378; -. [O60353-1]
DR ProteomicsDB; 4963; -.
DR Antibodypedia; 2906; 350 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 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; HAVAWGM; -.
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 1070 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 174 other tissues.
DR ExpressionAtlas; O60353; baseline and differential.
DR Genevisible; O60353; HS.
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:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:BHF-UCL.
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; cd07450; CRD_FZ6; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR000539; Frizzled/Smoothened_TM.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR041770; FZ6_CRD.
DR InterPro; IPR026543; FZD6.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF75; PTHR11309:SF75; 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; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
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
