ID FZD4_HUMAN Reviewed; 537 AA. AC Q9ULV1; A8K9Q3; Q14C97; Q6S9E4; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 24-JAN-2024, entry version 208. DE RecName: Full=Frizzled-4; DE Short=Fz-4; DE Short=hFz4; DE AltName: Full=FzE4; DE AltName: CD_antigen=CD344; DE Flags: Precursor; GN Name=FZD4; 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], AND TISSUE SPECIFICITY. RC TISSUE=Fetal lung; RX PubMed=10544037; DOI=10.1006/bbrc.1999.1612; RA Kirikoshi H., Sagara N., Koike J., Tanaka K., Sekihara H., Hirai M., RA Katoh M.; RT "Molecular cloning and characterization of human frizzled-4 on chromosome RT 11q14-q21."; RL Biochem. Biophys. Res. Commun. 264:955-961(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; 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=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 257-318. 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 [7] 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 [8] RP INTERACTION WITH GPC3. RX PubMed=24496449; DOI=10.1242/jcs.140871; RA Capurro M., Martin T., Shi W., Filmus J.; RT "Glypican-3 binds to Frizzled and plays a direct role in the stimulation of RT canonical Wnt signaling."; RL J. Cell Sci. 127:1565-1575(2014). RN [9] {ECO:0007744|PDB:6BD4} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 178-517, FUNCTION, SUBCELLULAR RP LOCATION, TRANSMEMBRANE DOMAINS, DISULFIDE BONDS, CHARACTERIZATION OF RP VARIANTS ARG-181 AND TYR-204, AND MUTAGENESIS OF SER-233; TYR-250; ARG-253; RP TYR-265; TYR-269; GLU-341; ASP-371; TYR-378; ASN-381; LEU-399; SER-418; RP TYR-444; TYR-455; GLU-458; GLU-477; LYS-480; TRP-494 AND TRP-496. RX PubMed=30135577; DOI=10.1038/s41586-018-0447-x; RA Yang S., Wu Y., Xu T.H., de Waal P.W., He Y., Pu M., Chen Y., RA DeBruine Z.J., Zhang B., Zaidi S.A., Popov P., Guo Y., Han G.W., Lu Y., RA Suino-Powell K., Dong S., Harikumar K.G., Miller L.J., Katritch V., RA Xu H.E., Shui W., Stevens R.C., Melcher K., Zhao S., Xu F.; RT "Crystal structure of the Frizzled 4 receptor in a ligand-free state."; RL Nature 560:666-670(2018). RN [10] RP VARIANT EVR1 493-MET-TRP-494 DEL, AND CHARACTERIZATION OF VARIANT EVR1 RP 493-MET-TRP-494 DEL. RX PubMed=12172548; DOI=10.1038/ng957; RA Robitaille J., MacDonald M.L.E., Kaykas A., Sheldahl L.C., Zeisler J., RA Dube M.-P., Zhang L.-H., Singaraja R.R., Guernsey D.L., Zheng B., RA Siebert L.F., Hoskin-Mott A., Trese M.T., Pimstone S.N., Shastry B.S., RA Moon R.T., Hayden M.R., Goldberg Y.P., Samuels M.E.; RT "Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative RT vitreoretinopathy."; RL Nat. Genet. 32:326-330(2002). RN [11] RP VARIANTS EVR1 TYR-69; VAL-105; GLN-417 AND ASP-488. RX PubMed=14507768; DOI=10.1136/bjo.87.10.1291; RA Kondo H., Hayashi H., Oshima K., Tahira T., Hayashi K.; RT "Frizzled 4 gene (FZD4) mutations in patients with familial exudative RT vitreoretinopathy with variable expressivity."; RL Br. J. Ophthalmol. 87:1291-1295(2003). RN [12] RP VARIANT EVR1 VAL-342. RX PubMed=15488808; DOI=10.1016/j.ajo.2004.05.001; RA Yoshida S., Arita R., Yoshida A., Tada H., Emori A., Noda Y., Nakao S., RA Fujisawa K., Ishibashi T.; RT "Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative RT vitreoretinopathy."; RL Am. J. Ophthalmol. 138:670-671(2004). RN [13] RP VARIANTS EVR1 VAL-105 AND VAL-157, AND CHARACTERIZATION OF VARIANTS EVR1 RP VAL-105; VAL-157 AND 493-MET-TRP-494 DEL. RX PubMed=15035989; DOI=10.1016/s0092-8674(04)00216-8; RA Xu Q., Wang Y., Dabdoub A., Smallwood P.M., Williams J., Woods C., RA Kelley M.W., Jiang L., Tasman W., Zhang K., Nathans J.; RT "Vascular development in the retina and inner ear: control by Norrin and RT Frizzled-4, a high-affinity ligand-receptor pair."; RL Cell 116:883-895(2004). RN [14] RP VARIANTS EVR1 ASP-36; THR-105; VAL-157 AND PHE-497, AND VARIANT SER-168. RX PubMed=15223780; DOI=10.1167/iovs.03-1044; RA Toomes C., Bottomley H.M., Scott S., Mackey D.A., Craig J.E., RA Appukuttan B., Stout J.T., Flaxel C.J., Zhang K., Black G.C.M., Fryer A., RA Downey L.M., Inglehearn C.F.; RT "Spectrum and frequency of FZD4 mutations in familial exudative RT vitreoretinopathy."; RL Invest. Ophthalmol. Vis. Sci. 45:2083-2090(2004). RN [15] RP VARIANTS EVR1 TYR-69 AND ARG-181. RX PubMed=15370539; DOI=10.1080/13816810490514270; RA Omoto S., Hayashi T., Kitahara K., Takeuchi T., Ueoka Y.; RT "Autosomal dominant familial exudative vitreoretinopathy in two Japanese RT families with FZD4 mutations (H69Y and C181R)."; RL Ophthalmic Genet. 25:81-90(2004). RN [16] RP VARIANTS EVR1 SER-33 AND VAL-256, AND VARIANT SER-168. RX PubMed=15733276; DOI=10.1111/j.1399-0004.2005.00408.x; RA MacDonald M.L., Goldberg Y.P., Macfarlane J., Samuels M.E., Trese M.T., RA Shastry B.S.; RT "Genetic variants of frizzled-4 gene in familial exudative RT vitreoretinopathy and advanced retinopathy of prematurity."; RL Clin. Genet. 67:363-366(2005). RN [17] RP VARIANTS EVR1 TYR-69; VAL-105; CYS-335; VAL-342; GLN-417 AND ASP-488. RX PubMed=15981244; DOI=10.1002/humu.20191; RA Qin M., Hayashi H., Oshima K., Tahira T., Hayashi K., Kondo H.; RT "Complexity of the genotype-phenotype correlation in familial exudative RT vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes."; RL Hum. Mutat. 26:104-112(2005). RN [18] RP VARIANTS EVR1 SER-33 AND ARG-204. RX PubMed=17093393; RA Nallathambi J., Shukla D., Rajendran A., Namperumalsamy P., RA Muthulakshmi R., Sundaresan P.; RT "Identification of novel FZD4 mutations in Indian patients with familial RT exudative vitreoretinopathy."; RL Mol. Vis. 12:1086-1092(2006). RN [19] RP VARIANT [LARGE SCALE ANALYSIS] THR-436. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [20] RP CHARACTERIZATION OF VARIANTS EVR1 VAL-105 AND GLN-417, AND CHARACTERIZATION RP OF VARIANT TYR-69. RX PubMed=17955262; DOI=10.1007/s00439-007-0438-8; RA Qin M., Kondo H., Tahira T., Hayashi K.; RT "Moderate reduction of Norrin signaling activity associated with the RT causative missense mutations identified in patients with familial exudative RT vitreoretinopathy."; RL Hum. Genet. 122:615-623(2008). RN [21] RP VARIANTS EVR1 SER-33; LYS-223 AND PRO-445, AND VARIANT SER-168. RX PubMed=19324841; DOI=10.1167/iovs.08-3320; RA Boonstra F.N., van Nouhuys C.E., Schuil J., de Wijs I.J., RA van der Donk K.P., Nikopoulos K., Mukhopadhyay A., Scheffer H., RA Tilanus M.A.D., Cremers F.P.M., Hoefsloot L.H.; RT "Clinical and molecular evaluation of probands and family members with RT familial exudative vitreoretinopathy."; RL Invest. Ophthalmol. Vis. Sci. 50:4379-4385(2009). RN [22] RP VARIANTS EVR1 THR-114 AND 493-MET-TRP-494 DEL. RX PubMed=19172507; DOI=10.1080/13816810802464312; RA Robitaille J.M., Wallace K., Zheng B., Beis M.J., Samuels M., RA Hoskin-Mott A., Guernsey D.L.; RT "Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with RT persistent fetal vasculature (PFV) caused by FZD4 mutations in two distinct RT pedigrees."; RL Ophthalmic Genet. 30:23-30(2009). RN [23] RP VARIANTS EVR1 GLN-40; TYR-204 AND ARG-525. RX PubMed=20340138; DOI=10.1002/humu.21250; RA Nikopoulos K., Venselaar H., Collin R.W.J., Riveiro-Alvarez R., RA Boonstra F.N., Hooymans J.M., Mukhopadhyay A., Shears D., van Bers M., RA de Wijs I.J., van Essen A.J., Sijmons R.H., Tilanus M.A.D., RA van Nouhuys C.E., Ayuso C., Hoefsloot L.H., Cremers F.P.M.; RT "Overview of the mutation spectrum in familial exudative vitreoretinopathy RT and Norrie disease with identification of 21 novel variants in FZD4, LRP5, RT and NDP."; RL Hum. Mutat. 31:656-666(2010). RN [24] RP VARIANTS RETINOPATHY OF PREMATURITY ASN-203 AND GLY-370. RX PubMed=20141357; DOI=10.3109/13816810903479834; RA Ells A., Guernsey D.L., Wallace K., Zheng B., Vincer M., Allen A., RA Ingram A., DaSilva O., Siebert L., Sheidow T., Beis J., Robitaille J.M.; RT "Severe retinopathy of prematurity associated with FZD4 mutations."; RL Ophthalmic Genet. 31:37-43(2010). CC -!- FUNCTION: Receptor for Wnt proteins (PubMed:30135577). Most frizzled CC receptors are coupled to the beta-catenin (CTNNB1) canonical signaling CC pathway, which leads to the activation of disheveled proteins, CC inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin CC (CTNNB1) and activation of Wnt target genes (PubMed:30135577). Plays a CC critical role in retinal vascularization by acting as a receptor for CC Wnt proteins and norrin (NDP) (By similarity). In retina, it can be CC activated by Wnt protein-binding and also by Wnt-independent signaling CC via binding of norrin (NDP), promoting in both cases beta-catenin CC (CTNNB1) accumulation and stimulation of LEF/TCF-mediated CC transcriptional programs (By similarity). A second signaling pathway CC involving PKC and calcium fluxes has been seen for some family members, CC but it is not yet clear if it represents a distinct pathway or if it CC can be integrated in the canonical pathway, as PKC seems to be required CC for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to CC involve interactions with G-proteins. May be involved in transduction CC and intercellular transmission of polarity information during tissue CC morphogenesis and/or in differentiated tissues. CC {ECO:0000250|UniProtKB:Q61088, ECO:0000269|PubMed:30135577}. CC -!- SUBUNIT: Interacts with MAGI3 and NDP (By similarity). Component of a CC complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (By CC similarity). Interacts (via FZ domain) with TSKU; TSKU competes with CC WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing CC peripheral eye development (By similarity). Interacts with glypican CC GPC3 (PubMed:24496449). {ECO:0000250|UniProtKB:Q61088, CC ECO:0000269|PubMed:24496449}. CC -!- INTERACTION: CC Q9ULV1; P01023: A2M; NbExp=3; IntAct=EBI-2466380, EBI-640741; CC Q9ULV1; G5E9A7: DMWD; NbExp=3; IntAct=EBI-2466380, EBI-10976677; CC Q9ULV1; P50570-2: DNM2; NbExp=3; IntAct=EBI-2466380, EBI-10968534; CC Q9ULV1; P42858: HTT; NbExp=9; IntAct=EBI-2466380, EBI-466029; CC Q9ULV1; Q00604: NDP; NbExp=4; IntAct=EBI-2466380, EBI-2466352; CC Q9ULV1; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2466380, EBI-5235340; CC Q9ULV1; G3GTH2: Slc9a3r1; Xeno; NbExp=2; IntAct=EBI-2466380, EBI-3504975; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30135577}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Almost ubiquitous (PubMed:10544037). Largely CC expressed in adult heart, skeletal muscle, ovary, and fetal kidney CC (PubMed:10544037). Moderate amounts in adult liver, kidney, pancreas, CC spleen, and fetal lung, and small amounts in placenta, adult lung, CC prostate, testis, colon, fetal brain and liver (PubMed:10544037). CC {ECO:0000269|PubMed:10544037}. 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:0000269|PubMed:22575959}. CC -!- DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: A disorder CC of the retinal vasculature characterized by an abrupt cessation of CC growth of peripheral capillaries, leading to an avascular peripheral CC retina. This may lead to compensatory retinal neovascularization, which CC is thought to be induced by hypoxia from the initial avascular insult. CC New vessels are prone to leakage and rupture causing exudates and CC bleeding, followed by scarring, retinal detachment and blindness. CC Clinical features can be highly variable, even within the same family. CC Patients with mild forms of the disease are asymptomatic, and their CC only disease related abnormality is an arc of avascular retina in the CC extreme temporal periphery. In many ways the disease resembles CC retinopathy of prematurity but there is no evidence of prematurity or CC small birth weight in the patient history. CC {ECO:0000269|PubMed:12172548, ECO:0000269|PubMed:14507768, CC ECO:0000269|PubMed:15035989, ECO:0000269|PubMed:15223780, CC ECO:0000269|PubMed:15370539, ECO:0000269|PubMed:15488808, CC ECO:0000269|PubMed:15733276, ECO:0000269|PubMed:15981244, CC ECO:0000269|PubMed:17093393, ECO:0000269|PubMed:17955262, CC ECO:0000269|PubMed:19172507, ECO:0000269|PubMed:19324841, CC ECO:0000269|PubMed:20340138}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; AB032417; BAA86286.1; -; mRNA. DR EMBL; AY462097; AAR23924.1; -; mRNA. DR EMBL; AK292768; BAF85457.1; -; mRNA. DR EMBL; AP001528; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC114527; AAI14528.1; -; mRNA. DR EMBL; BC114622; AAI14623.1; -; mRNA. DR CCDS; CCDS8279.1; -. DR PIR; JC7127; JC7127. DR RefSeq; NP_036325.2; NM_012193.3. DR PDB; 5BPB; X-ray; 2.20 A; A/B/C/D=42-179. DR PDB; 5BPQ; X-ray; 2.40 A; A/B/C/D=42-179. DR PDB; 5BQC; X-ray; 3.00 A; B=42-179. DR PDB; 5BQE; X-ray; 2.30 A; C=42-179. DR PDB; 5CL1; X-ray; 3.80 A; C/D=38-160. DR PDB; 5CM4; X-ray; 2.40 A; A/B=40-164. DR PDB; 5UWG; X-ray; 2.56 A; A/B=40-164. DR PDB; 6BD4; X-ray; 2.40 A; A=178-517. DR PDB; 6NE1; X-ray; 3.01 A; A=42-161. DR PDBsum; 5BPB; -. DR PDBsum; 5BPQ; -. DR PDBsum; 5BQC; -. DR PDBsum; 5BQE; -. DR PDBsum; 5CL1; -. DR PDBsum; 5CM4; -. DR PDBsum; 5UWG; -. DR PDBsum; 6BD4; -. DR PDBsum; 6NE1; -. DR AlphaFoldDB; Q9ULV1; -. DR SMR; Q9ULV1; -. DR BioGRID; 113918; 20. DR CORUM; Q9ULV1; -. DR IntAct; Q9ULV1; 13. DR MINT; Q9ULV1; -. DR STRING; 9606.ENSP00000434034; -. DR ChEMBL; CHEMBL4523491; -. DR GuidetoPHARMACOLOGY; 232; -. DR GlyConnect; 2003; 5 N-Linked glycans (1 site). DR GlyCosmos; Q9ULV1; 2 sites, 5 glycans. DR GlyGen; Q9ULV1; 2 sites, 5 N-linked glycans (1 site). DR iPTMnet; Q9ULV1; -. DR PhosphoSitePlus; Q9ULV1; -. DR BioMuta; FZD4; -. DR DMDM; 62298045; -. DR jPOST; Q9ULV1; -. DR MassIVE; Q9ULV1; -. DR MaxQB; Q9ULV1; -. DR PaxDb; 9606-ENSP00000434034; -. DR PeptideAtlas; Q9ULV1; -. DR ProteomicsDB; 85129; -. DR ABCD; Q9ULV1; 21 sequenced antibodies. DR Antibodypedia; 17696; 583 antibodies from 40 providers. DR DNASU; 8322; -. DR Ensembl; ENST00000531380.2; ENSP00000434034.1; ENSG00000174804.4. DR GeneID; 8322; -. DR KEGG; hsa:8322; -. DR MANE-Select; ENST00000531380.2; ENSP00000434034.1; NM_012193.4; NP_036325.2. DR UCSC; uc001pce.4; human. DR AGR; HGNC:4042; -. DR CTD; 8322; -. DR DisGeNET; 8322; -. DR GeneCards; FZD4; -. DR HGNC; HGNC:4042; FZD4. DR HPA; ENSG00000174804; Tissue enhanced (adipose). DR MalaCards; FZD4; -. DR MIM; 133780; phenotype. DR MIM; 604579; gene. DR neXtProt; NX_Q9ULV1; -. DR OpenTargets; ENSG00000174804; -. DR Orphanet; 891; Familial exudative vitreoretinopathy. DR Orphanet; 91495; Persistent hyperplastic primary vitreous. DR Orphanet; 90050; Retinopathy of prematurity. DR PharmGKB; PA28459; -. DR VEuPathDB; HostDB:ENSG00000174804; -. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000157141; -. DR HOGENOM; CLU_007873_2_1_1; -. DR InParanoid; Q9ULV1; -. DR OMA; HWGEFRA; -. DR OrthoDB; 5483535at2759; -. DR PhylomeDB; Q9ULV1; -. DR TreeFam; TF317907; -. DR PathwayCommons; Q9ULV1; -. 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-4641263; Regulation of FZD by ubiquitination. DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4. DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR SignaLink; Q9ULV1; -. DR SIGNOR; Q9ULV1; -. DR BioGRID-ORCS; 8322; 13 hits in 1159 CRISPR screens. DR ChiTaRS; FZD4; human. DR GeneWiki; FZD4; -. DR GenomeRNAi; 8322; -. DR Pharos; Q9ULV1; Tchem. DR PRO; PR:Q9ULV1; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9ULV1; Protein. DR Bgee; ENSG00000174804; Expressed in adipose tissue and 175 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0001540; F:amyloid-beta binding; IPI:ARUK-UCL. DR GO; GO:0019955; F:cytokine binding; IPI:BHF-UCL. DR GO; GO:0004896; F:cytokine receptor activity; IDA:BHF-UCL. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0038023; F:signaling receptor activity; ISS:ARUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0042813; F:Wnt receptor activity; IDA:WormBase. DR GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB. DR GO; GO:0061301; P:cerebellum vasculature morphogenesis; IEA:Ensembl. DR GO; GO:0045446; P:endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0060856; P:establishment of blood-brain barrier; IEA:Ensembl. DR GO; GO:0035426; P:extracellular matrix-cell signaling; IEA:Ensembl. DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl. DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IMP:BHF-UCL. 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:0110135; P:Norrin signaling pathway; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL. DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0150012; P:positive regulation of neuron projection arborization; ISS:ARUK-UCL. DR GO; GO:0042701; P:progesterone secretion; IEA:Ensembl. DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IMP:BHF-UCL. DR GO; GO:0061304; P:retinal blood vessel morphogenesis; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR GO; GO:0016055; P:Wnt signaling pathway; ISS:ARUK-UCL. DR GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; IDA:BHF-UCL. DR CDD; cd15038; 7tmF_FZD4; 1. DR CDD; cd07448; CRD_FZ4; 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; IPR041765; FZ4_CRD. DR InterPro; IPR026551; FZD4_7TM. DR InterPro; IPR017981; GPCR_2-like_7TM. DR PANTHER; PTHR11309; FRIZZLED; 1. DR PANTHER; PTHR11309:SF23; FRIZZLED-4; 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; Q9ULV1; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Developmental protein; Disease variant; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; KW Receptor; Reference proteome; Signal; Transducer; Transmembrane; KW Transmembrane helix; Ubl conjugation; Wnt signaling pathway. FT SIGNAL 1..36 FT /evidence="ECO:0000255" FT CHAIN 37..537 FT /note="Frizzled-4" FT /id="PRO_0000012985" FT TOPO_DOM 37..212 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 213..243 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 244..249 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 250..275 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 276..299 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 300..333 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 334..336 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 337..365 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 366..383 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 384..418 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 419..431 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 432..460 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 461..473 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:30135577" FT TRANSMEM 474..495 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:30135577" FT TOPO_DOM 496..537 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:30135577" FT DOMAIN 40..161 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT MOTIF 499..504 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 535..537 FT /note="PDZ-binding" FT CARBOHYD 59 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 144 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 45..106 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 53..99 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 90..128 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 117..158 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 121..145 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 181..200 FT /evidence="ECO:0000269|PubMed:30135577" FT DISULFID 204..282 FT /evidence="ECO:0000269|PubMed:30135577" FT DISULFID 302..377 FT /evidence="ECO:0000269|PubMed:30135577" FT VARIANT 33 FT /note="P -> S (in EVR1; benign; dbSNP:rs61735304)" FT /evidence="ECO:0000269|PubMed:15733276, FT ECO:0000269|PubMed:17093393, ECO:0000269|PubMed:19324841" FT /id="VAR_063920" FT VARIANT 36 FT /note="G -> D (in EVR1; dbSNP:rs80358281)" FT /evidence="ECO:0000269|PubMed:15223780" FT /id="VAR_063921" FT VARIANT 40 FT /note="E -> Q (in EVR1; dbSNP:rs139401671)" FT /evidence="ECO:0000269|PubMed:20340138" FT /id="VAR_063922" FT VARIANT 69 FT /note="H -> Y (in EVR1; minor reduction of its wild-type FT activity; dbSNP:rs80358282)" FT /evidence="ECO:0000269|PubMed:14507768, FT ECO:0000269|PubMed:15370539, ECO:0000269|PubMed:15981244, FT ECO:0000269|PubMed:17955262" FT /id="VAR_063923" FT VARIANT 105 FT /note="M -> T (in EVR1; dbSNP:rs80358285)" FT /evidence="ECO:0000269|PubMed:15223780" FT /id="VAR_063924" FT VARIANT 105 FT /note="M -> V (in EVR1; loss of function; FT dbSNP:rs80358284)" FT /evidence="ECO:0000269|PubMed:14507768, FT ECO:0000269|PubMed:15035989, ECO:0000269|PubMed:15981244, FT ECO:0000269|PubMed:17955262" FT /id="VAR_038947" FT VARIANT 114 FT /note="I -> T (in EVR1)" FT /evidence="ECO:0000269|PubMed:19172507" FT /id="VAR_063925" FT VARIANT 157 FT /note="M -> V (in EVR1; loss of function; FT dbSNP:rs80358286)" FT /evidence="ECO:0000269|PubMed:15035989, FT ECO:0000269|PubMed:15223780" FT /id="VAR_038948" FT VARIANT 168 FT /note="P -> S (in dbSNP:rs61735303)" FT /evidence="ECO:0000269|PubMed:15223780, FT ECO:0000269|PubMed:15733276, ECO:0000269|PubMed:19324841" FT /id="VAR_063926" FT VARIANT 181 FT /note="C -> R (in EVR1; increased signaling activity; FT dbSNP:rs80358287)" FT /evidence="ECO:0000269|PubMed:15370539, FT ECO:0000269|PubMed:30135577" FT /id="VAR_063927" FT VARIANT 203 FT /note="K -> N (in retinopathy of prematurity; FT dbSNP:rs1476724511)" FT /evidence="ECO:0000269|PubMed:20141357" FT /id="VAR_063928" FT VARIANT 204 FT /note="C -> R (in EVR1; reduced signaling activity in FT presence of WNT3A but no change in presence of NDP/norrin; FT dbSNP:rs80358288)" FT /evidence="ECO:0000269|PubMed:17093393, FT ECO:0000269|PubMed:30135577" FT /id="VAR_063929" FT VARIANT 204 FT /note="C -> Y (in EVR1; dbSNP:rs1064794064)" FT /evidence="ECO:0000269|PubMed:20340138" FT /id="VAR_063930" FT VARIANT 223 FT /note="M -> K (in EVR1)" FT /evidence="ECO:0000269|PubMed:19324841" FT /id="VAR_063931" FT VARIANT 256 FT /note="I -> V (in EVR1; dbSNP:rs104894223)" FT /evidence="ECO:0000269|PubMed:15733276" FT /id="VAR_063932" FT VARIANT 335 FT /note="W -> C (in EVR1; dbSNP:rs80358292)" FT /evidence="ECO:0000269|PubMed:15981244" FT /id="VAR_063933" FT VARIANT 342 FT /note="M -> V (in EVR1; dbSNP:rs80358293)" FT /evidence="ECO:0000269|PubMed:15488808, FT ECO:0000269|PubMed:15981244" FT /id="VAR_063934" FT VARIANT 370 FT /note="A -> G (in retinopathy of prematurity)" FT /evidence="ECO:0000269|PubMed:20141357" FT /id="VAR_063935" FT VARIANT 417 FT /note="R -> Q (in EVR1; 48% loss of its wild-type activity; FT associated in a EVR4 patient with mutation Cys-444 in LPR5; FT dbSNP:rs80358294)" FT /evidence="ECO:0000269|PubMed:14507768, FT ECO:0000269|PubMed:15981244, ECO:0000269|PubMed:17955262" FT /id="VAR_063936" FT VARIANT 436 FT /note="K -> T (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036413" FT VARIANT 445 FT /note="T -> P (in EVR1; dbSNP:rs80358297)" FT /evidence="ECO:0000269|PubMed:19324841" FT /id="VAR_063937" FT VARIANT 488 FT /note="G -> D (in EVR1; dbSNP:rs80358298)" FT /evidence="ECO:0000269|PubMed:14507768, FT ECO:0000269|PubMed:15981244" FT /id="VAR_063938" FT VARIANT 493..494 FT /note="Missing (in EVR1; loss of function)" FT /evidence="ECO:0000269|PubMed:12172548, FT ECO:0000269|PubMed:15035989, ECO:0000269|PubMed:19172507" FT /id="VAR_017777" FT VARIANT 497 FT /note="S -> F (in EVR1; dbSNP:rs80358300)" FT /evidence="ECO:0000269|PubMed:15223780" FT /id="VAR_063939" FT VARIANT 525 FT /note="G -> R (in EVR1)" FT /evidence="ECO:0000269|PubMed:20340138" FT /id="VAR_063940" FT MUTAGEN 233 FT /note="S->A: Increased signaling activity in presence of FT NDP/norrin but not in presence of WNT3A." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 233 FT /note="S->F: Slightly increased signaling activity in FT presence of NDP/norrin and reduced signaling in presence of FT WNT3A." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 250 FT /note="Y->F: Reduced signaling activity in presence of FT NDP/norrin." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 250 FT /note="Y->F: Reduced signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 253 FT /note="R->C: Reduced signaling activity in presence of FT NDP/norrin." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 265 FT /note="Y->A: Slight increase in signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 269 FT /note="Y->A: Increased signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 341 FT /note="E->A: Reduced signaling activity in presence of FT NDP/norrin." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 371 FT /note="D->A: No effect on signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 378 FT /note="Y->A: Increased signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 381 FT /note="N->A: Slight increase in signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 399 FT /note="L->F: No effect on signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 418 FT /note="S->N: Increased signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 444 FT /note="Y->A,F: Reduced signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 455 FT /note="Y->A: Increased signaling activity in presence of FT WNT3A but not in presence of NDP/norrin." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 458 FT /note="E->A: No effect on signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 477 FT /note="E->A: Increased signaling activity in presence of FT WNT3A but not in presence of NDP/norrin." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 480 FT /note="K->A: Increased signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 494 FT /note="W->L: Reduced signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT MUTAGEN 496 FT /note="W->A: Reduced signaling activity." FT /evidence="ECO:0000269|PubMed:30135577" FT CONFLICT 481 FT /note="I -> T (in Ref. 1; BAA86286)" FT /evidence="ECO:0000305" FT CONFLICT 500 FT /note="T -> S (in Ref. 1; BAA86286)" FT /evidence="ECO:0000305" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:5BQC" FT HELIX 51..53 FT /evidence="ECO:0007829|PDB:5BPB" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:5BPB" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:5BQC" FT HELIX 72..79 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 83..88 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 94..102 FT /evidence="ECO:0007829|PDB:5BPB" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:5BPB" FT STRAND 110..114 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 118..134 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:5BPB" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:5BPB" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:5BQC" FT TURN 186..190 FT /evidence="ECO:0007829|PDB:6BD4" FT STRAND 197..201 FT /evidence="ECO:0007829|PDB:6BD4" FT STRAND 205..211 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 213..243 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 245..247 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 250..252 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 253..275 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 277..281 FT /evidence="ECO:0007829|PDB:6BD4" FT STRAND 282..289 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 300..330 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 337..341 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 344..365 FT /evidence="ECO:0007829|PDB:6BD4" FT STRAND 368..370 FT /evidence="ECO:0007829|PDB:6BD4" FT TURN 372..374 FT /evidence="ECO:0007829|PDB:6BD4" FT STRAND 377..382 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 384..390 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 392..417 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 432..443 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 445..460 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 462..467 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 474..489 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 492..495 FT /evidence="ECO:0007829|PDB:6BD4" FT HELIX 498..511 FT /evidence="ECO:0007829|PDB:6BD4" SQ SEQUENCE 537 AA; 59881 MW; E0A83ECEC560A381 CRC64; MAWRGAGPSV PGAPGGVGLS LGLLLQLLLL LGPARGFGDE EERRCDPIRI SMCQNLGYNV TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS VYVPMCTEKI NIPIGPCGGM CLSVKRRCEP VLKEFGFAWP ESLNCSKFPP QNDHNHMCME GPGDEEVPLP HKTPIQPGEE CHSVGTNSDQ YIWVKRSLNC VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTAFTVLT FLIDSSRFSY PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA AWAIPAVKTI VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV IGTLFIAAGL VALFKIRSNL QKDGTKTDKL ERLMVKIGVF SVLYTVPATC VIACYFYEIS NWALFRYSAD DSNMAVEMLK IFMSLLVGIT SGMWIWSAKT LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGSETVV //