Q9ULV1 (FZD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-4
Short name=Fz-4
Short name=hFz4

Alternative name(s):
FzE4
CD_antigen=CD344

Gene names

Name:

FZD4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	537 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.
Subunit structure	Interacts with MAGI3 and norrin (NDP). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) By similarity.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Almost ubiquitous. Largely expressed in adult heart, skeletal muscle, ovary, and fetal kidney. Moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and small amounts in placenta, adult lung, prostate, testis, colon, fetal brain and liver.
Domain	Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway By similarity. The FZ domain is involved in binding with Wnt ligands By similarity.
Post-translational modification	Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. Ref.7
Involvement in disease	Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Belongs to the G-protein coupled receptor Fz/Smo family. Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway, calcium modulating pathway Inferred from direct assay Ref.8. Source: BHF-UCL brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 20802536. Source: UniProtKB cellular response to retinoic acid Inferred from sequence or structural similarity. Source: UniProtKB cerebellum vasculature morphogenesis Inferred from electronic annotation. Source: Compara embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular matrix-cell signaling Inferred from electronic annotation. Source: Compara locomotion involved in locomotory behavior Inferred from electronic annotation. Source: Compara negative regulation of cell-substrate adhesion Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 14688793. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.11Ref.18. Source: BHF-UCL progesterone secretion Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of vascular endothelial growth factor receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome retina vasculature morphogenesis in camera-type eye Inferred from mutant phenotype Ref.8PubMed 15024691. Source: BHF-UCL retinal blood vessel morphogenesis Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara substrate adhesion-dependent cell spreading Inferred from Biological aspect of Ancestor. Source: RefGenome vasculogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cell projection Inferred from Biological aspect of Ancestor. Source: RefGenome cell surface Inferred from direct assay PubMed 19643732. Source: BHF-UCL cell-cell junction Inferred from electronic annotation. Source: Compara cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to plasma membrane Inferred by curator Ref.18. Source: BHF-UCL
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW PDZ domain binding Inferred from direct assay PubMed 20802536. Source: UniProtKB Wnt-activated receptor activity Inferred from direct assay Ref.18. Source: BHF-UCL Wnt-protein binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
I79_000956	G3GTH2	2	EBI-2466380,EBI-3504975	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 36	36	Potential
	Chain	37 – 537	501	Frizzled-4		PRO_0000012985
Regions
	Topological domain	37 – 222	186	Extracellular Potential
	Transmembrane	223 – 243	21	Helical; Name=1; Potential
	Topological domain	244 – 254	11	Cytoplasmic Potential
	Transmembrane	255 – 275	21	Helical; Name=2; Potential
	Topological domain	276 – 302	27	Extracellular Potential
	Transmembrane	303 – 323	21	Helical; Name=3; Potential
	Topological domain	324 – 344	21	Cytoplasmic Potential
	Transmembrane	345 – 365	21	Helical; Name=4; Potential
	Topological domain	366 – 389	24	Extracellular Potential
	Transmembrane	390 – 410	21	Helical; Name=5; Potential
	Topological domain	411 – 436	26	Cytoplasmic Potential
	Transmembrane	437 – 457	21	Helical; Name=6; Potential
	Topological domain	458 – 477	20	Extracellular Potential
	Transmembrane	478 – 498	21	Helical; Name=7; Potential
	Topological domain	499 – 537	39	Cytoplasmic Potential
	Domain	40 – 161	122	FZ
	Motif	499 – 504	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	535 – 537	3	PDZ-binding
Amino acid modifications
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Disulfide bond	45 ↔ 106		By similarity
	Disulfide bond	53 ↔ 99		By similarity
	Disulfide bond	90 ↔ 128		By similarity
	Disulfide bond	117 ↔ 158		By similarity
	Disulfide bond	121 ↔ 145		By similarity
Natural variations
	Natural variant	33	1	P → S in EVR1. Ref.14 Ref.16 Ref.19		VAR_063920
	Natural variant	36	1	G → D in EVR1. Ref.12		VAR_063921
	Natural variant	40	1	E → Q in EVR1. Ref.21		VAR_063922
	Natural variant	69	1	H → Y in EVR1; minor reduction of its wild-type activity. Ref.9 Ref.13 Ref.15 Ref.18		VAR_063923
	Natural variant	105	1	M → T in EVR1. Ref.12		VAR_063924
	Natural variant	105	1	M → V in EVR1; loss of function. Ref.9 Ref.11 Ref.15 Ref.18		VAR_038947
	Natural variant	114	1	I → T in EVR1. Ref.20		VAR_063925
	Natural variant	157	1	M → V in EVR1; loss of function. Ref.11 Ref.12		VAR_038948
	Natural variant	168	1	P → S. Ref.12 Ref.14 Ref.19		VAR_063926
	Natural variant	181	1	C → R in EVR1. Ref.13		VAR_063927
	Natural variant	203	1	K → N in retinopathy of prematurity. Ref.22		VAR_063928
	Natural variant	204	1	C → R in EVR1. Ref.16		VAR_063929
	Natural variant	204	1	C → Y in EVR1. Ref.21		VAR_063930
	Natural variant	223	1	M → K in EVR1. Ref.19		VAR_063931
	Natural variant	256	1	I → V in EVR1. Ref.14		VAR_063932
	Natural variant	335	1	W → C in EVR1. Ref.15		VAR_063933
	Natural variant	342	1	M → V in EVR1. Ref.10 Ref.15		VAR_063934
	Natural variant	370	1	A → G in retinopathy of prematurity. Ref.22		VAR_063935
	Natural variant	417	1	R → Q in EVR1; 48% loss of its wild-type activity; associated in a EVR4 patient with mutation CYS-444 in LPR5. Ref.9 Ref.15 Ref.18		VAR_063936
	Natural variant	436	1	K → T in a colorectal cancer sample; somatic mutation. Ref.17		VAR_036413
	Natural variant	445	1	T → P in EVR1. Ref.19		VAR_063937
	Natural variant	488	1	G → D in EVR1. Ref.9 Ref.15		VAR_063938
	Natural variant	493 – 494	2	Missing in EVR1; loss of function.		VAR_017777
	Natural variant	497	1	S → F in EVR1. Ref.12		VAR_063939
	Natural variant	525	1	G → R in EVR1. Ref.21		VAR_063940
Experimental info
	Sequence conflict	481	1	I → T in BAA86286. Ref.1
	Sequence conflict	500	1	T → S in BAA86286. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9ULV1 [UniParc]. Last modified March 29, 2005. Version 2. Checksum: E0A83ECEC560A381	FASTA	537	59,881
	10 20 30 40 50 60 MAWRGAGPSV PGAPGGVGLS LGLLLQLLLL LGPARGFGDE EERRCDPIRI SMCQNLGYNV 70 80 90 100 110 120 TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS VYVPMCTEKI NIPIGPCGGM 130 140 150 160 170 180 CLSVKRRCEP VLKEFGFAWP ESLNCSKFPP QNDHNHMCME GPGDEEVPLP HKTPIQPGEE 190 200 210 220 230 240 CHSVGTNSDQ YIWVKRSLNC VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTAFTVLT 250 260 270 280 290 300 FLIDSSRFSY PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT 310 320 330 340 350 360 GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA AWAIPAVKTI 370 380 390 400 410 420 VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV IGTLFIAAGL VALFKIRSNL 430 440 450 460 470 480 QKDGTKTDKL ERLMVKIGVF SVLYTVPATC VIACYFYEIS NWALFRYSAD DSNMAVEMLK 490 500 510 520 530 IFMSLLVGIT SGMWIWSAKT LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGSETVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21." Kirikoshi H., Sagara N., Koike J., Tanaka K., Sekihara H., Hirai M., Katoh M. Biochem. Biophys. Res. Commun. 264:955-961(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal lung.
[2]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals." Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K. Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 257-318. Tissue: Esophageal carcinoma.
[7]	"ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner." Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F. Nature 485:195-200(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY ZNRF3.
[8]	"Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy." Robitaille J., MacDonald M.L.E., Kaykas A., Sheldahl L.C., Zeisler J., Dube M.-P., Zhang L.-H., Singaraja R.R., Guernsey D.L., Zheng B., Siebert L.F., Hoskin-Mott A., Trese M.T., Pimstone S.N., Shastry B.S., Moon R.T., Hayden M.R., Goldberg Y.P., Samuels M.E. Nat. Genet. 32:326-330(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EVR1 493-MET-TRP-494 DEL, CHARACTERIZATION OF VARIANT EVR1 493-MET-TRP-494 DEL.
[9]	"Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity." Kondo H., Hayashi H., Oshima K., Tahira T., Hayashi K. Br. J. Ophthalmol. 87:1291-1295(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 TYR-69; VAL-105; GLN-417 AND ASP-488.
[10]	"Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy." Yoshida S., Arita R., Yoshida A., Tada H., Emori A., Noda Y., Nakao S., Fujisawa K., Ishibashi T. Am. J. Ophthalmol. 138:670-671(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EVR1 VAL-342.
[11]	"Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair." Xu Q., Wang Y., Dabdoub A., Smallwood P.M., Williams J., Woods C., Kelley M.W., Jiang L., Tasman W., Zhang K., Nathans J. Cell 116:883-895(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 VAL-105 AND VAL-157, CHARACTERIZATION OF VARIANTS EVR1 VAL-105; VAL-157 AND 493-MET-TRP-494 DEL.
[12]	"Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy." Toomes C., Bottomley H.M., Scott S., Mackey D.A., Craig J.E., Appukuttan B., Stout J.T., Flaxel C.J., Zhang K., Black G.C.M., Fryer A., Downey L.M., Inglehearn C.F. Invest. Ophthalmol. Vis. Sci. 45:2083-2090(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 ASP-36; THR-105; VAL-157 AND PHE-497, VARIANT SER-168.
[13]	"Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R)." Omoto S., Hayashi T., Kitahara K., Takeuchi T., Ueoka Y. Ophthalmic Genet. 25:81-90(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 TYR-69 AND ARG-181.
[14]	"Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity." MacDonald M.L., Goldberg Y.P., Macfarlane J., Samuels M.E., Trese M.T., Shastry B.S. Clin. Genet. 67:363-366(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 SER-33 AND VAL-256, VARIANT SER-168.
[15]	"Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes." Qin M., Hayashi H., Oshima K., Tahira T., Hayashi K., Kondo H. Hum. Mutat. 26:104-112(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 TYR-69; VAL-105; CYS-335; VAL-342; GLN-417 AND ASP-488.
[16]	"Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy." Nallathambi J., Shukla D., Rajendran A., Namperumalsamy P., Muthulakshmi R., Sundaresan P. Mol. Vis. 12:1086-1092(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 SER-33 AND ARG-204.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-436.
[18]	"Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy." Qin M., Kondo H., Tahira T., Hayashi K. Hum. Genet. 122:615-623(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS EVR1 VAL-105 AND GLN-417, CHARACTERIZATION OF VARIANT TYR-69.
[19]	"Clinical and molecular evaluation of probands and family members with familial exudative vitreoretinopathy." Boonstra F.N., van Nouhuys C.E., Schuil J., de Wijs I.J., van der Donk K.P., Nikopoulos K., Mukhopadhyay A., Scheffer H., Tilanus M.A.D., Cremers F.P.M., Hoefsloot L.H. Invest. Ophthalmol. Vis. Sci. 50:4379-4385(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 SER-33; LYS-223 AND PRO-445, VARIANT SER-168.
[20]	"Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with persistent fetal vasculature (PFV) caused by FZD4 mutations in two distinct pedigrees." Robitaille J.M., Wallace K., Zheng B., Beis M.J., Samuels M., Hoskin-Mott A., Guernsey D.L. Ophthalmic Genet. 30:23-30(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 THR-114 AND 493-MET-TRP-494 DEL.
[21]	"Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP." Nikopoulos K., Venselaar H., Collin R.W.J., Riveiro-Alvarez R., Boonstra F.N., Hooymans J.M., Mukhopadhyay A., Shears D., van Bers M., de Wijs I.J., van Essen A.J., Sijmons R.H., Tilanus M.A.D., van Nouhuys C.E., Ayuso C., Hoefsloot L.H., Cremers F.P.M. Hum. Mutat. 31:656-666(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EVR1 GLN-40; TYR-204 AND ARG-525.
[22]	"Severe retinopathy of prematurity associated with FZD4 mutations." Ells A., Guernsey D.L., Wallace K., Zheng B., Vincer M., Allen A., Ingram A., DaSilva O., Siebert L., Sheidow T., Beis J., Robitaille J.M. Ophthalmic Genet. 31:37-43(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RETINOPATHY OF PREMATURITY ASN-203 AND GLY-370.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB032417 mRNA. Translation: BAA86286.1. AY462097 mRNA. Translation: AAR23924.1. AK292768 mRNA. Translation: BAF85457.1. AP001528 Genomic DNA. No translation available. BC114527 mRNA. Translation: AAI14528.1. BC114622 mRNA. Translation: AAI14623.1.
IPI	IPI00977659.
PIR	JC7127.
RefSeq	NP_036325.2. NM_012193.3.
UniGene	Hs.591968.
3D structure databases
ProteinModelPortal	Q9ULV1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9ULV1. 6 interactions.
STRING	9606.ENSP00000311581.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9ULV1.
Polymorphism databases
DMDM	62298045.
Proteomic databases
PaxDb	Q9ULV1.
PRIDE	Q9ULV1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000531380; ENSP00000434034; ENSG00000174804.
GeneID	8322.
KEGG	hsa:8322.
UCSC	uc001pce.3. human.
Organism-specific databases
CTD	8322.
GeneCards	GC11M086656.
HGNC	HGNC:4042. FZD4.
HPA	HPA042328.
MIM	133780. phenotype. 604579. gene.
neXtProt	NX_Q9ULV1.
Orphanet	891. Familial exudative vitreoretinopathy. 91495. Persistent hyperplastic primary vitreous. 90050. Retinopathy of prematurity.
PharmGKB	PA28459.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG284049.
HOGENOM	HOG000233236.
HOVERGEN	HBG006977.
InParanoid	Q9ULV1.
KO	K02354.
OMA	SMCLSVK.
OrthoDB	EOG4KPT9H.
PhylomeDB	Q9ULV1.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9ULV1.
Bgee	Q9ULV1.
CleanEx	HS_FZD4.
Genevestigator	Q9ULV1.
GermOnline	ENSG00000174804. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026551. FZD4. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF23. PTHR11309:SF23. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8322.
NextBio	31163.
SOURCE	Search...

Entry information

Entry name

FZD4_HUMAN

Accession

Primary (citable) accession number: Q9ULV1
Secondary accession number(s): A8K9Q3, Q14C97, Q6S9E4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	March 29, 2005
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.