ID FZD5_HUMAN Reviewed; 585 AA. AC Q13467; A8K2X1; B2RCZ1; Q53R22; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 212. DE RecName: Full=Frizzled-5; DE Short=Fz-5; DE Short=hFz5; DE AltName: Full=FzE5; DE Flags: Precursor; GN Name=FZD5; Synonyms=C2orf31; 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]. RC TISSUE=Retina; RX PubMed=8626800; DOI=10.1074/jbc.271.8.4468; RA Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J., RA Copeland N.G., Jenkins N.A., Nathans J.; RT "A large family of putative transmembrane receptors homologous to the RT product of the Drosophila tissue polarity gene frizzled."; RL J. Biol. Chem. 271:4468-4476(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=11408929; DOI=10.3892/ijo.19.1.105; RA Saitoh T., Hirai M., Katoh M.; RT "Molecular cloning and characterization of human Frizzled-5 gene on RT chromosome 2q33.3-q34 region."; RL Int. J. Oncol. 19:105-110(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen, and Umbilical cord blood; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 273-331. RC TISSUE=Esophageal carcinoma; RX PubMed=9707618; DOI=10.1073/pnas.95.17.10164; RA Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.; RT "A novel frizzled gene identified in human esophageal carcinoma mediates RT APC/beta-catenin signals."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998). RN [6] RP FUNCTION, AND COUPLING TO BETA-CATENIN PATHWAY. RX PubMed=9054360; DOI=10.1126/science.275.5306.1652; RA He X., Saint-Jeannet J.P., Wang Y., Nathans J., Dawid I., Varmus H.; RT "A member of the Frizzled protein family mediating axis induction by Wnt- RT 5A."; RL Science 275:1652-1654(1997). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10097073; DOI=10.1073/pnas.96.7.3546; RA Hsieh J.C., Rattner A., Smallwood P.M., Nathans J.; RT "Biochemical characterization of Wnt-frizzled interactions using a soluble, RT biologically active vertebrate Wnt protein."; RL Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999). RN [8] RP INTERACTION WITH WNT2B. RX PubMed=12490564; DOI=10.1242/dev.00244; RA Kubo F., Takeichi M., Nakagawa S.; RT "Wnt2b controls retinal cell differentiation at the ciliary marginal RT zone."; RL Development 130:587-598(2003). RN [9] RP INTERACTION WITH WNT7A. RX PubMed=18230341; DOI=10.1016/j.bbrc.2008.01.088; RA Carmon K.S., Loose D.S.; RT "Wnt7a interaction with Fzd5 and detection of signaling activation using a RT split eGFP."; RL Biochem. Biophys. Res. Commun. 368:285-291(2008). RN [10] RP FUNCTION, AND INTERACTION WITH WNT7A. RX PubMed=20530549; DOI=10.1242/dev.046722; RA Sahores M., Gibb A., Salinas P.C.; RT "Frizzled-5, a receptor for the synaptic organizer Wnt7a, regulates RT activity-mediated synaptogenesis."; RL Development 137:2215-2225(2010). RN [11] 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 [12] RP UBIQUITINATION BY RNF43. RX PubMed=22895187; DOI=10.1038/nature11308; RA Koo B.K., Spit M., Jordens I., Low T.Y., Stange D.E., van de Wetering M., RA van Es J.H., Mohammed S., Heck A.J., Maurice M.M., Clevers H.; RT "Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis RT of Wnt receptors."; RL Nature 488:665-669(2012). RN [13] {ECO:0007744|PDB:5URY, ECO:0007744|PDB:5URZ} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 28-155 IN COMPLEX WITH RP UNSATURATED FATTY ACID, SUBUNIT, GLYCOSYLATION AT ASN-47, AND DISULFIDE RP BONDS. RX PubMed=28377511; DOI=10.1073/pnas.1618293114; RA Nile A.H., Mukund S., Stanger K., Wang W., Hannoush R.N.; RT "Unsaturated fatty acyl recognition by Frizzled receptors mediates RT dimerization upon Wnt ligand binding."; RL Proc. Natl. Acad. Sci. U.S.A. 114:4147-4152(2017). CC -!- FUNCTION: Receptor for Wnt proteins (PubMed:9054360, PubMed:10097073, CC PubMed:20530549). Can activate WNT2, WNT10B, WNT5A, but not WNT2B or CC WNT4 (in vitro); the in vivo situation may be different since not all CC of these are known to be coexpressed (By similarity). In neurons, CC activation of WNT7A promotes formation of synapses (PubMed:20530549). CC Functions in the canonical Wnt/beta-catenin signaling pathway. The CC canonical Wnt/beta-catenin signaling pathway leads to the activation of CC disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation CC of beta-catenin and activation of Wnt target genes (By similarity). A CC second signaling pathway involving PKC and calcium fluxes has been seen CC for some family members, but it is not yet clear if it represents a CC distinct pathway or if it can be integrated in the canonical pathway, CC as PKC seems to be required for Wnt-mediated inactivation of GSK-3 CC kinase. Both pathways seem to involve interactions with G-proteins. May CC be involved in transduction and intercellular transmission of polarity CC information during tissue morphogenesis and/or in differentiated CC tissues (Probable). Plays a role in yolk sac angiogenesis and in CC placental vascularization (By similarity). CC {ECO:0000250|UniProtKB:Q9EQD0, ECO:0000269|PubMed:10097073, CC ECO:0000269|PubMed:20530549, ECO:0000269|PubMed:9054360, ECO:0000305}. CC -!- SUBUNIT: Binding of unsaturated fatty acid molecules (via FZ domain) CC promotes homodimerization (PubMed:28377511). Interacts with WNT2B CC (PubMed:12490564). Interacts with WNT7A (PubMed:18230341, CC PubMed:20530549). Interacts with GOPC (By similarity). CC {ECO:0000250|UniProtKB:Q9EQD0, ECO:0000269|PubMed:12490564, CC ECO:0000269|PubMed:18230341, ECO:0000269|PubMed:20530549, CC ECO:0000269|PubMed:28377511}. CC -!- INTERACTION: CC Q13467; Q6P3W7: SCYL2; NbExp=4; IntAct=EBI-3913027, EBI-1046810; CC Q13467; P78383: SLC35B1; NbExp=3; IntAct=EBI-3913027, EBI-12147661; CC Q13467; M4NKV9: tcdB; Xeno; NbExp=3; IntAct=EBI-3913027, EBI-20596828; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8CHL0}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8CHL0}. Golgi CC apparatus membrane {ECO:0000250|UniProtKB:Q9EQD0}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:Q9EQD0}. Synapse CC {ECO:0000250|UniProtKB:Q8CHL0}. Perikaryon CC {ECO:0000250|UniProtKB:Q8CHL0}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:Q8CHL0}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q8CHL0}. Note=Localized at the plasma membrane CC and also found at the Golgi. {ECO:0000250|UniProtKB:Q9EQD0}. CC -!- DOMAIN: The PDZ-binding motif mediates interaction with GOPC. CC {ECO:0000250}. 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 RNF43 and ZNRF3, leading to its degradation by CC the proteasome. {ECO:0000269|PubMed:22575959, CC ECO:0000269|PubMed:22895187}. 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; U43318; AAC50385.1; -; mRNA. DR EMBL; AB043702; BAB60959.1; -; mRNA. DR EMBL; AK290386; BAF83075.1; -; mRNA. DR EMBL; AK315338; BAG37738.1; -; mRNA. DR EMBL; AC096772; AAY24058.1; -; Genomic_DNA. DR CCDS; CCDS33366.1; -. DR RefSeq; NP_003459.2; NM_003468.3. DR PDB; 5URY; X-ray; 2.10 A; A/B=28-155. DR PDB; 5URZ; X-ray; 2.20 A; A/B=28-155. DR PDB; 6O39; X-ray; 1.80 A; C=28-150. DR PDB; 6WW2; EM; 3.70 A; R=27-428, R=441-546. DR PDBsum; 5URY; -. DR PDBsum; 5URZ; -. DR PDBsum; 6O39; -. DR PDBsum; 6WW2; -. DR AlphaFoldDB; Q13467; -. DR SMR; Q13467; -. DR BioGRID; 113609; 20. DR CORUM; Q13467; -. DR IntAct; Q13467; 17. DR MINT; Q13467; -. DR STRING; 9606.ENSP00000354607; -. DR ChEMBL; CHEMBL3559687; -. DR GuidetoPHARMACOLOGY; 233; -. DR GlyCosmos; Q13467; 3 sites, 1 glycan. DR GlyGen; Q13467; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q13467; -. DR PhosphoSitePlus; Q13467; -. DR BioMuta; FZD5; -. DR DMDM; 116242481; -. DR EPD; Q13467; -. DR jPOST; Q13467; -. DR MassIVE; Q13467; -. DR MaxQB; Q13467; -. DR PaxDb; 9606-ENSP00000354607; -. DR PeptideAtlas; Q13467; -. DR ProteomicsDB; 59463; -. DR TopDownProteomics; Q13467; -. DR ABCD; Q13467; 61 sequenced antibodies. DR Antibodypedia; 19996; 474 antibodies from 36 providers. DR DNASU; 7855; -. DR Ensembl; ENST00000295417.4; ENSP00000354607.3; ENSG00000163251.4. DR GeneID; 7855; -. DR KEGG; hsa:7855; -. DR MANE-Select; ENST00000295417.4; ENSP00000354607.3; NM_003468.4; NP_003459.2. DR UCSC; uc002vcj.4; human. DR AGR; HGNC:4043; -. DR CTD; 7855; -. DR DisGeNET; 7855; -. DR GeneCards; FZD5; -. DR HGNC; HGNC:4043; FZD5. DR HPA; ENSG00000163251; Tissue enhanced (liver). DR MalaCards; FZD5; -. DR MIM; 601723; gene. DR neXtProt; NX_Q13467; -. DR OpenTargets; ENSG00000163251; -. DR Orphanet; 98942; Coloboma of choroid and retina. DR Orphanet; 98943; Coloboma of eye lens. DR Orphanet; 98946; Coloboma of eyelid. DR Orphanet; 98944; Coloboma of iris. DR Orphanet; 98945; Coloboma of macula. DR Orphanet; 98947; Coloboma of optic disc. DR PharmGKB; PA28460; -. DR VEuPathDB; HostDB:ENSG00000163251; -. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000162639; -. DR HOGENOM; CLU_007873_2_0_1; -. DR InParanoid; Q13467; -. DR OMA; NCAIPCY; -. DR OrthoDB; 5483535at2759; -. DR PhylomeDB; Q13467; -. DR TreeFam; TF317907; -. DR PathwayCommons; Q13467; -. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR Reactome; R-HSA-4086398; Ca2+ pathway. DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins. DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR Reactome; R-HSA-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2. DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants. DR SignaLink; Q13467; -. DR SIGNOR; Q13467; -. DR BioGRID-ORCS; 7855; 24 hits in 1164 CRISPR screens. DR ChiTaRS; FZD5; human. DR GeneWiki; FZD5; -. DR GenomeRNAi; 7855; -. DR Pharos; Q13467; Tbio. DR PRO; PR:Q13467; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q13467; Protein. DR Bgee; ENSG00000163251; Expressed in jejunal mucosa and 176 other cell types or tissues. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell. DR GO; GO:0001540; F:amyloid-beta binding; IPI:ARUK-UCL. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0042813; F:Wnt receptor activity; IDA:FlyBase. DR GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IDA:BHF-UCL. DR GO; GO:0060561; P:apoptotic process involved in morphogenesis; IEA:Ensembl. DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; IDA:BHF-UCL. DR GO; GO:0060718; P:chorionic trophoblast cell differentiation; IEA:Ensembl. DR GO; GO:0000578; P:embryonic axis specification; IDA:BHF-UCL. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0002071; P:glandular epithelial cell maturation; IEA:Ensembl. DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl. DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:ARUK-UCL. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0002726; P:positive regulation of T cell cytokine production; IDA:CACAO. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IMP:BHF-UCL. DR GO; GO:0031077; P:post-embryonic camera-type eye development; IEA:Ensembl. DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IEA:Ensembl. DR GO; GO:1901382; P:regulation of chorionic trophoblast cell proliferation; IEA:Ensembl. DR GO; GO:1901524; P:regulation of mitophagy; HMP:ParkinsonsUK-UCL. DR GO; GO:0060061; P:Spemann organizer formation; IDA:BHF-UCL. DR GO; GO:0007416; P:synapse assembly; TAS:ParkinsonsUK-UCL. DR GO; GO:0060715; P:syncytiotrophoblast cell differentiation involved in labyrinthine layer development; IEA:Ensembl. DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl. DR CDD; cd15249; 7tmF_FZD5; 1. DR CDD; cd07460; CRD_FZ5; 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; IPR037441; FZ5_CRD. DR InterPro; IPR017981; GPCR_2-like_7TM. DR PANTHER; PTHR11309; FRIZZLED; 1. DR PANTHER; PTHR11309:SF136; FRIZZLED-5; 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; Q13467; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Developmental protein; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Golgi apparatus; KW Lipid-binding; Membrane; Receptor; Reference proteome; Signal; Synapse; KW Transducer; Transmembrane; Transmembrane helix; Ubl conjugation; KW Wnt signaling pathway. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..585 FT /note="Frizzled-5" FT /id="PRO_0000012990" FT TOPO_DOM 27..238 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 239..259 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 260..270 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 271..291 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 292..315 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 316..336 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 337..358 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 359..379 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 380..402 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 403..423 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 424..449 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 450..470 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 471..500 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 501..521 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 522..585 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 28..150 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT REGION 156..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 525..530 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 MOTIF 583..585 FT /note="PDZ-binding" FT COMPBIAS 160..177 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 47 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:28377511, FT ECO:0007744|PDB:5URY, ECO:0007744|PDB:5URZ" FT CARBOHYD 151 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 33..94 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090, FT ECO:0000269|PubMed:28377511, ECO:0007744|PDB:5URY, FT ECO:0007744|PDB:5URZ" FT DISULFID 41..87 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090, FT ECO:0000269|PubMed:28377511, ECO:0007744|PDB:5URY, FT ECO:0007744|PDB:5URZ" FT DISULFID 78..116 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090, FT ECO:0000269|PubMed:28377511, ECO:0007744|PDB:5URY, FT ECO:0007744|PDB:5URZ" FT DISULFID 105..147 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090, FT ECO:0000269|PubMed:28377511, ECO:0007744|PDB:5URY, FT ECO:0007744|PDB:5URZ" FT DISULFID 109..133 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090, FT ECO:0000269|PubMed:28377511, ECO:0007744|PDB:5URY, FT ECO:0007744|PDB:5URZ" FT VARIANT 216 FT /note="P -> L (in dbSNP:rs35994626)" FT /id="VAR_049291" FT CONFLICT 88 FT /note="S -> T (in Ref. 1; AAC50385)" FT /evidence="ECO:0000305" FT CONFLICT 262..263 FT /note="ER -> DT (in Ref. 1; AAC50385)" FT /evidence="ECO:0000305" FT CONFLICT 345 FT /note="G -> A (in Ref. 1; AAC50385)" FT /evidence="ECO:0000305" FT CONFLICT 357 FT /note="A -> G (in Ref. 1; AAC50385)" FT /evidence="ECO:0000305" FT CONFLICT 384 FT /note="D -> G (in Ref. 4; BAF83075)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="G -> R (in Ref. 1; AAC50385)" FT /evidence="ECO:0000305" FT CONFLICT 504 FT /note="M -> V (in Ref. 4; BAG37738)" FT /evidence="ECO:0000305" FT HELIX 39..41 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 60..67 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 71..76 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 82..90 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 106..122 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 129..131 FT /evidence="ECO:0007829|PDB:6O39" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:6O39" FT TURN 139..141 FT /evidence="ECO:0007829|PDB:6O39" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:6O39" SQ SEQUENCE 585 AA; 64507 MW; AC3AB2CD912C1B0A CRC64; MARPDPSAPP SLLLLLLAQL VGRAAAASKA PVCQEITVPM CRGIGYNLTH MPNQFNHDTQ DEAGLEVHQF WPLVEIQCSP DLRFFLCSMY TPICLPDYHK PLPPCRSVCE RAKAGCSPLM RQYGFAWPER MSCDRLPVLG RDAEVLCMDY NRSEATTAPP RPFPAKPTLP GPPGAPASGG ECPAGGPFVC KCREPFVPIL KESHPLYNKV RTGQVPNCAV PCYQPSFSAD ERTFATFWIG LWSVLCFIST STTVATFLID MERFRYPERP IIFLSACYLC VSLGFLVRLV VGHASVACSR EHNHIHYETT GPALCTIVFL LVYFFGMASS IWWVILSLTW FLAAGMKWGN EAIAGYAQYF HLAAWLIPSV KSITALALSS VDGDPVAGIC YVGNQNLNSL RGFVLGPLVL YLLVGTLFLL AGFVSLFRIR SVIKQGGTKT DKLEKLMIRI GIFTLLYTVP ASIVVACYLY EQHYRESWEA ALTCACPGHD TGQPRAKPEY WVLMLKYFMC LVVGITSGVW IWSGKTVESW RRFTSRCCCR PRRGHKSGGA MAAGDYPEAS AALTGRTGPP GPAATYHKQV SLSHV //