FZD4_HUMAN
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 03-AUG-2022, entry version 200.
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: I79_000956; 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}.
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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 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; Q9ULV1; -.
DR PeptideAtlas; Q9ULV1; -.
DR PRIDE; Q9ULV1; -.
DR ProteomicsDB; 85129; -.
DR ABCD; Q9ULV1; 21 sequenced antibodies.
DR Antibodypedia; 17696; 543 antibodies from 39 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 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; 509772at2759; -.
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; 12 hits in 1080 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 173 other tissues.
DR Genevisible; Q9ULV1; HS.
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:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IC:BHF-UCL.
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:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB.
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:0035426; P:extracellular matrix-cell signaling; IEA:Ensembl.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
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; TAS:ARUK-UCL.
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:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; ISS:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-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: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; cd07448; CRD_FZ4; 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; IPR041765; FZ4_CRD.
DR InterPro; IPR026551; FZD4.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF23; PTHR11309:SF23; 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 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 variant; 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
