FZD4
entrez
8322
canonical
uniprot
Q9ULV1
canonical
ensembl
ENSG00000174804
resolver
ensp
ENSP00000434034
resolver
enst
ENST00000531380
resolver
genesymbol
FZD4
resolver
hgnc
HGNC:4042
resolver
uniprot
A8K9Q3
resolver
uniprot
Q14C97
resolver
uniprot
Q6S9E4
resolver
uniprot_entry
FZD4_HUMAN
resolver
uniprot_sec
A8K9Q3
resolver
uniprot_sec
Q14C97
resolver
uniprot_sec
Q6S9E4
resolver
amino_acid_sequence
MAWRGAGPSVPGAPGGVGLSLGLLLQLLLLLGPARGFGDEEERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEVPLPHKTPIQPGEECHSVGTNSDQYIWVKRSLNCVLKCGYDAGLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAAEPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIACYFYEISNWALFRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNSGKVKREKRGNGWVKPGKGSETVV
uniprot
proteins
disease_involvement
DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: An autosomal dominant 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. {ECO:0000269|PubMed:12172548, ECO:0000269|PubMed:14507768, ECO:0000269|PubMed:15035989, ECO:0000269|PubMed:15223780, ECO:0000269|PubMed:15370539, ECO:0000269|PubMed:15488808, ECO:0000269|PubMed:15733276, ECO:0000269|PubMed:15981244, ECO:0000269|PubMed:17093393, ECO:0000269|PubMed:17955262, ECO:0000269|PubMed:19172507, ECO:0000269|PubMed:19324841, ECO:0000269|PubMed:20340138}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Receptor for Wnt proteins (PubMed:30135577). Most 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 (PubMed:30135577). Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (By similarity). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs (By similarity). 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. {ECO:0000250|UniProtKB:Q61088, ECO:0000269|PubMed:30135577}.
uniprot
proteins
mass_dalton
59881
uniprot
proteins
mutagenesis
MUTAGEN 233; /note="S->A: Increased signaling activity in presence of NDP/norrin but not in presence of WNT3A."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 233; /note="S->F: Slightly increased signaling activity in presence of NDP/norrin and reduced signaling in presence of WNT3A."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 250; /note="Y->F: Reduced signaling activity in presence of NDP/norrin."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 250; /note="Y->F: Reduced signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 253; /note="R->C: Reduced signaling activity in presence of NDP/norrin."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 265; /note="Y->A: Slight increase in signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 269; /note="Y->A: Increased signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 341; /note="E->A: Reduced signaling activity in presence of NDP/norrin."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 371; /note="D->A: No effect on signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 378; /note="Y->A: Increased signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 381; /note="N->A: Slight increase in signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 399; /note="L->F: No effect on signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 418; /note="S->N: Increased signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 444; /note="Y->A,F: Reduced signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 455; /note="Y->A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 458; /note="E->A: No effect on signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 477; /note="E->A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 480; /note="K->A: Increased signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 494; /note="W->L: Reduced signaling activity."; /evidence="ECO:0000269|PubMed:30135577"; MUTAGEN 496; /note="W->A: Reduced signaling activity."; /evidence="ECO:0000269|PubMed:30135577
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. {ECO:0000269|PubMed:22575959}.
uniprot
proteins
protein_family
G protein-coupled receptor Fz/Smo family
uniprot
proteins
pubmed
10544037
uniprot
proteins
pubmed
12172548
uniprot
proteins
pubmed
14507768
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15035989
uniprot
proteins
pubmed
15223780
uniprot
proteins
pubmed
15370539
uniprot
proteins
pubmed
15488808
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15733276
uniprot
proteins
pubmed
15981244
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17093393
uniprot
proteins
pubmed
17955262
uniprot
proteins
pubmed
19172507
uniprot
proteins
pubmed
19324841
uniprot
proteins
pubmed
20141357
uniprot
proteins
pubmed
20340138
uniprot
proteins
pubmed
22575959
uniprot
proteins
pubmed
24496449
uniprot
proteins
pubmed
30135577
uniprot
proteins
pubmed
9707618
uniprot
proteins
sequence_length
537
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30135577}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 213..243; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 250..275; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 300..333; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 337..365; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 384..418; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 432..460; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:30135577"; TRANSMEM 474..495; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:30135577
uniprot
proteins