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Q9ULV1 (FZD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-4

Short name=Fz-4
Short name=hFz4
Alternative name(s):
FzE4
CD_antigen=CD344
Gene names
Name:FZD4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length537 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processWnt signaling pathway
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from direct assay PubMed 14688793Ref.18. Source: BHF-UCL

Wnt 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 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: Ensembl

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular matrix-cell signaling

Inferred from electronic annotation. Source: Ensembl

locomotion involved in locomotory behavior

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14688793. Source: BHF-UCL

positive regulation of transcription, DNA-templated

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: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

substrate adhesion-dependent cell spreading

Inferred from Biological aspect of Ancestor. Source: RefGenome

vasculogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcell 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: Ensembl

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of plasma membrane

Inferred by curator Ref.18. Source: BHF-UCL

plasma membrane

Inferred from direct assay Ref.8PubMed 14688793Ref.11. Source: BHF-UCL

   Molecular_functionG-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

cytokine binding

Inferred from physical interaction Ref.18. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction PubMed 14688793. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction PubMed 14688793. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

I79_000956G3GTH22EBI-2466380,EBI-3504975From a different organism.
NDPQ006044EBI-2466380,EBI-2466352

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3636 Potential
Chain37 – 537501Frizzled-4
PRO_0000012985

Regions

Topological domain37 – 222186Extracellular Potential
Transmembrane223 – 24321Helical; Name=1; Potential
Topological domain244 – 25411Cytoplasmic Potential
Transmembrane255 – 27521Helical; Name=2; Potential
Topological domain276 – 30227Extracellular Potential
Transmembrane303 – 32321Helical; Name=3; Potential
Topological domain324 – 34421Cytoplasmic Potential
Transmembrane345 – 36521Helical; Name=4; Potential
Topological domain366 – 38924Extracellular Potential
Transmembrane390 – 41021Helical; Name=5; Potential
Topological domain411 – 43626Cytoplasmic Potential
Transmembrane437 – 45721Helical; Name=6; Potential
Topological domain458 – 47720Extracellular Potential
Transmembrane478 – 49821Helical; Name=7; Potential
Topological domain499 – 53739Cytoplasmic Potential
Domain40 – 161122FZ
Motif499 – 5046Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif535 – 5373PDZ-binding

Amino acid modifications

Glycosylation591N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Disulfide bond45 ↔ 106 By similarity
Disulfide bond53 ↔ 99 By similarity
Disulfide bond90 ↔ 128 By similarity
Disulfide bond117 ↔ 158 By similarity
Disulfide bond121 ↔ 145 By similarity

Natural variations

Natural variant331P → S in EVR1. Ref.14 Ref.16 Ref.19
Corresponds to variant rs61735304 [ dbSNP | Ensembl ].
VAR_063920
Natural variant361G → D in EVR1. Ref.12
VAR_063921
Natural variant401E → Q in EVR1. Ref.21
VAR_063922
Natural variant691H → Y in EVR1; minor reduction of its wild-type activity. Ref.9 Ref.13 Ref.15 Ref.18
Corresponds to variant rs80358282 [ dbSNP | Ensembl ].
VAR_063923
Natural variant1051M → T in EVR1. Ref.12
VAR_063924
Natural variant1051M → V in EVR1; loss of function. Ref.9 Ref.11 Ref.15 Ref.18
VAR_038947
Natural variant1141I → T in EVR1. Ref.20
VAR_063925
Natural variant1571M → V in EVR1; loss of function. Ref.11 Ref.12
VAR_038948
Natural variant1681P → S. Ref.12 Ref.14 Ref.19
Corresponds to variant rs61735303 [ dbSNP | Ensembl ].
VAR_063926
Natural variant1811C → R in EVR1. Ref.13
VAR_063927
Natural variant2031K → N in retinopathy of prematurity. Ref.22
VAR_063928
Natural variant2041C → R in EVR1. Ref.16
VAR_063929
Natural variant2041C → Y in EVR1. Ref.21
VAR_063930
Natural variant2231M → K in EVR1. Ref.19
VAR_063931
Natural variant2561I → V in EVR1. Ref.14
VAR_063932
Natural variant3351W → C in EVR1. Ref.15
VAR_063933
Natural variant3421M → V in EVR1. Ref.10 Ref.15
VAR_063934
Natural variant3701A → G in retinopathy of prematurity. Ref.22
VAR_063935
Natural variant4171R → 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 variant4361K → T in a colorectal cancer sample; somatic mutation. Ref.17
VAR_036413
Natural variant4451T → P in EVR1. Ref.19
VAR_063937
Natural variant4881G → D in EVR1. Ref.9 Ref.15
VAR_063938
Natural variant493 – 4942Missing in EVR1; loss of function.
VAR_017777
Natural variant4971S → F in EVR1. Ref.12
VAR_063939
Natural variant5251G → R in EVR1. Ref.21
VAR_063940

Experimental info

Sequence conflict4811I → T in BAA86286. Ref.1
Sequence conflict5001T → S in BAA86286. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9ULV1 [UniParc].

Last modified March 29, 2005. Version 2.
Checksum: E0A83ECEC560A381

FASTA53759,881
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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

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.
PIRJC7127.
RefSeqNP_036325.2. NM_012193.3.
UniGeneHs.591968.

3D structure databases

ProteinModelPortalQ9ULV1.
SMRQ9ULV1. Positions 45-149, 193-511.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113918. 6 interactions.
IntActQ9ULV1. 7 interactions.
MINTMINT-2822299.
STRING9606.ENSP00000311581.

Protein family/group databases

MEROPSI93.001.
GPCRDBSearch...

PTM databases

PhosphoSiteQ9ULV1.

Polymorphism databases

DMDM62298045.

Proteomic databases

PaxDbQ9ULV1.
PRIDEQ9ULV1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000531380; ENSP00000434034; ENSG00000174804.
GeneID8322.
KEGGhsa:8322.
UCSCuc001pce.3. human.

Organism-specific databases

CTD8322.
GeneCardsGC11M086656.
HGNCHGNC:4042. FZD4.
HPAHPA042328.
MIM133780. phenotype.
604579. gene.
neXtProtNX_Q9ULV1.
Orphanet891. Familial exudative vitreoretinopathy.
91495. Persistent hyperplastic primary vitreous.
90050. Retinopathy of prematurity.
PharmGKBPA28459.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG284049.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidQ9ULV1.
KOK02354.
OMASMCLSVK.
OrthoDBEOG7M3J01.
PhylomeDBQ9ULV1.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9ULV1.

Gene expression databases

ArrayExpressQ9ULV1.
BgeeQ9ULV1.
CleanExHS_FZD4.
GenevestigatorQ9ULV1.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026551. FZD4.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF60. PTHR11309:SF60. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFZD4.
GenomeRNAi8322.
NextBio31163.
PROQ9ULV1.
SOURCESearch...

Entry information

Entry nameFZD4_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries