FZD4

Functionⁱ

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.

By similarity1 Publication

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, G-protein coupled receptor, Receptor, Transducer
Biological process	Wnt signaling pathway

Enzyme and pathway databases

PathwayCommonsⁱ	Q9ULV1
Reactomeⁱ	R-HSA-373080, Class B/2 (Secretin family receptors) R-HSA-4086398, Ca2+ pathway R-HSA-4608870, Asymmetric localization of PCP proteins R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-5099900, WNT5A-dependent internalization of FZD4 R-HSA-5340588, Signaling by RNF43 mutants R-HSA-8856825, Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828, Clathrin-mediated endocytosis
SignaLinkⁱ	Q9ULV1
SIGNORⁱ	Q9ULV1

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Frizzled-4 Short name: Fz-4 Short name: hFz4 Alternative name(s): FzE4 CD_antigen: CD344
Gene namesⁱ	Name:FZD4
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:4042, FZD4
MIMⁱ	604579, gene
neXtProtⁱ	NX_Q9ULV1
VEuPathDBⁱ	HostDB:ENSG00000174804

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	37 – 212	Extracellular1 PublicationAdd BLAST	176
Transmembraneⁱ	213 – 243	Helical; Name=11 PublicationAdd BLAST	31
Topological domainⁱ	244 – 249	Cytoplasmic1 Publication	6
Transmembraneⁱ	250 – 275	Helical; Name=21 PublicationAdd BLAST	26
Topological domainⁱ	276 – 299	Extracellular1 PublicationAdd BLAST	24
Transmembraneⁱ	300 – 333	Helical; Name=31 PublicationAdd BLAST	34
Topological domainⁱ	334 – 336	Cytoplasmic1 Publication	3
Transmembraneⁱ	337 – 365	Helical; Name=41 PublicationAdd BLAST	29
Topological domainⁱ	366 – 383	Extracellular1 PublicationAdd BLAST	18
Transmembraneⁱ	384 – 418	Helical; Name=51 PublicationAdd BLAST	35
Topological domainⁱ	419 – 431	Cytoplasmic1 PublicationAdd BLAST	13
Transmembraneⁱ	432 – 460	Helical; Name=61 PublicationAdd BLAST	29
Topological domainⁱ	461 – 473	Extracellular1 PublicationAdd BLAST	13
Transmembraneⁱ	474 – 495	Helical; Name=71 PublicationAdd BLAST	22
Topological domainⁱ	496 – 537	Cytoplasmic1 PublicationAdd BLAST	42

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Vitreoretinopathy, exudative 1 (EVR1)13 Publications

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionA 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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_063920	33	P → S in EVR1; benign variant. 3 PublicationsCorresponds to variant dbSNP:rs61735304EnsemblClinVar.	1
Natural variantⁱVAR_063921	36	G → D in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358281Ensembl.	1
Natural variantⁱVAR_063922	40	E → Q in EVR1. 1 PublicationCorresponds to variant dbSNP:rs139401671EnsemblClinVar.	1
Natural variantⁱVAR_063923	69	H → Y in EVR1; minor reduction of its wild-type activity. 4 PublicationsCorresponds to variant dbSNP:rs80358282EnsemblClinVar.	1
Natural variantⁱVAR_063924	105	M → T in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358285Ensembl.	1
Natural variantⁱVAR_038947	105	M → V in EVR1; loss of function. 4 PublicationsCorresponds to variant dbSNP:rs80358284EnsemblClinVar.	1
Natural variantⁱVAR_063925	114	I → T in EVR1. 1 Publication	1
Natural variantⁱVAR_038948	157	M → V in EVR1; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs80358286Ensembl.	1
Natural variantⁱVAR_063927	181	C → R in EVR1; increased signaling activity. 2 PublicationsCorresponds to variant dbSNP:rs80358287Ensembl.	1
Natural variantⁱVAR_063929	204	C → R in EVR1; reduced signaling activity in presence of WNT3A but no change in presence of NDP/norrin. 2 PublicationsCorresponds to variant dbSNP:rs80358288Ensembl.	1
Natural variantⁱVAR_063930	204	C → Y in EVR1. 1 PublicationCorresponds to variant dbSNP:rs1064794064EnsemblClinVar.	1
Natural variantⁱVAR_063931	223	M → K in EVR1. 1 Publication	1
Natural variantⁱVAR_063932	256	I → V in EVR1. 1 PublicationCorresponds to variant dbSNP:rs104894223EnsemblClinVar.	1
Natural variantⁱVAR_063933	335	W → C in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358292EnsemblClinVar.	1
Natural variantⁱVAR_063934	342	M → V in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358293EnsemblClinVar.	1
Natural variantⁱVAR_063936	417	R → Q in EVR1; 48% loss of its wild-type activity; associated in a EVR4 patient with mutation CYS-444 in LPR5. 3 PublicationsCorresponds to variant dbSNP:rs80358294EnsemblClinVar.	1
Natural variantⁱVAR_063937	445	T → P in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358297Ensembl.	1
Natural variantⁱVAR_063938	488	G → D in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358298Ensembl.	1
Natural variantⁱVAR_017777	493 – 494	Missing in EVR1; loss of function. 3 Publications	2
Natural variantⁱVAR_063939	497	S → F in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358300Ensembl.	1
Natural variantⁱVAR_063940	525	G → R in EVR1. 1 Publication	1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	233	S → A: Increased signaling activity in presence of NDP/norrin but not in presence of WNT3A. 1 Publication	1
Mutagenesisⁱ	233	S → F: Slightly increased signaling activity in presence of NDP/norrin and reduced signaling in presence of WNT3A. 1 Publication	1
Mutagenesisⁱ	250	Y → F: Reduced signaling activity in presence of NDP/norrin. 1 Publication	1
Mutagenesisⁱ	250	Y → F: Reduced signaling activity. 1 Publication	1
Mutagenesisⁱ	253	R → C: Reduced signaling activity in presence of NDP/norrin. 1 Publication	1
Mutagenesisⁱ	265	Y → A: Slight increase in signaling activity. 1 Publication	1
Mutagenesisⁱ	269	Y → A: Increased signaling activity. 1 Publication	1
Mutagenesisⁱ	341	E → A: Reduced signaling activity in presence of NDP/norrin. 1 Publication	1
Mutagenesisⁱ	371	D → A: No effect on signaling activity. 1 Publication	1
Mutagenesisⁱ	378	Y → A: Increased signaling activity. 1 Publication	1
Mutagenesisⁱ	381	N → A: Slight increase in signaling activity. 1 Publication	1
Mutagenesisⁱ	399	L → F: No effect on signaling activity. 1 Publication	1
Mutagenesisⁱ	418	S → N: Increased signaling activity. 1 Publication	1
Mutagenesisⁱ	444	Y → A or F: Reduced signaling activity. 1 Publication	1
Mutagenesisⁱ	455	Y → A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin. 1 Publication	1
Mutagenesisⁱ	458	E → A: No effect on signaling activity. 1 Publication	1
Mutagenesisⁱ	477	E → A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin. 1 Publication	1
Mutagenesisⁱ	480	K → A: Increased signaling activity. 1 Publication	1
Mutagenesisⁱ	494	W → L: Reduced signaling activity. 1 Publication	1
Mutagenesisⁱ	496	W → A: Reduced signaling activity. 1 Publication	1

Keywords - Diseaseⁱ

Disease variant

Organism-specific databases

DisGeNET More...DisGeNETⁱ	8322
MalaCards human disease database More...MalaCardsⁱ	FZD4
MIMⁱ	133780, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000174804
Orphanetⁱ	891, Familial exudative vitreoretinopathy 91495, Persistent hyperplastic primary vitreous 90050, Retinopathy of prematurity
PharmGKBⁱ	PA28459

Miscellaneous databases

Pharosⁱ	Q9ULV1, Tchem

Pharosⁱ

Q9ULV1, Tchem

Chemistry databases

ChEMBLⁱ	CHEMBL4523491
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	232

Genetic variation databases

BioMutaⁱ	FZD4
DMDMⁱ	62298045

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 36	Sequence analysisAdd BLAST		36
ChainⁱPRO_0000012985	37 – 537	Frizzled-4Add BLAST		501

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	45 ↔ 106	PROSITE-ProRule annotation
Disulfide bondⁱ	53 ↔ 99	PROSITE-ProRule annotation
Glycosylationⁱ	59	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	90 ↔ 128	PROSITE-ProRule annotation
Disulfide bondⁱ	117 ↔ 158	PROSITE-ProRule annotation
Disulfide bondⁱ	121 ↔ 145	PROSITE-ProRule annotation
Glycosylationⁱ	144	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	181 ↔ 200	1 Publication
Disulfide bondⁱ	204 ↔ 282	1 Publication
Disulfide bondⁱ	302 ↔ 377	1 Publication

Post-translational modificationⁱ

Keywords - PTMⁱ

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

jPOSTⁱ	Q9ULV1
MassIVEⁱ	Q9ULV1
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9ULV1
PaxDbⁱ	Q9ULV1
PeptideAtlas More...PeptideAtlasⁱ	Q9ULV1
PRIDEⁱ	Q9ULV1
ProteomicsDBⁱ	85129

PTM databases

GlyConnectⁱ	2003, 5 N-Linked glycans (1 site)
GlyGenⁱ	Q9ULV1, 2 sites, 5 N-linked glycans (1 site)
iPTMnetⁱ	Q9ULV1
PhosphoSitePlusⁱ	Q9ULV1

Expressionⁱ

Tissue specificityⁱ

Almost ubiquitous (PubMed:10544037). Largely expressed in adult heart, skeletal muscle, ovary, and fetal kidney (PubMed:10544037). 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 (PubMed:10544037).1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000174804, Expressed in right lung and 221 other tissues
Genevisibleⁱ	Q9ULV1, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000174804, Tissue enhanced (adipose)

HPAⁱ

ENSG00000174804, Tissue enhanced (adipose)

Interactionⁱ

Subunit structureⁱ

Interacts with MAGI3 and NDP (By similarity).

Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (By similarity).

Interacts (via FZ domain) with TSKU; TSKU competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (By similarity).

Interacts with glypican GPC3 (PubMed:24496449).

By similarity1 Publication

Binary interactionsⁱ

Hide details

Q9ULV1

With	#Exp.	IntAct
A2M [P01023]	3	EBI-2466380,EBI-640741
DMWD [G5E9A7]	3	EBI-2466380,EBI-10976677
DNM2 - isoform 2 [P50570-2]	3	EBI-2466380,EBI-10968534
HTT [P42858]	9	EBI-2466380,EBI-466029
NDP [Q00604]	4	EBI-2466380,EBI-2466352
SPRED1 [Q7Z699]	3	EBI-2466380,EBI-5235340
I79_000956 [G3GTH2] from Cricetulus griseus.	2	EBI-2466380,EBI-3504975

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	113918, 20 interactors
CORUMⁱ	Q9ULV1
IntActⁱ	Q9ULV1, 13 interactors
Molecular INTeraction database More...MINTⁱ	Q9ULV1
STRINGⁱ	9606.ENSP00000434034

Miscellaneous databases

RNActⁱ	Q9ULV1, protein

RNActⁱ

Q9ULV1, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	45 – 47	Combined sources	3
Helixⁱ	51 – 53	Combined sources	3
Beta strandⁱ	55 – 57	Combined sources	3
Beta strandⁱ	59 – 61	Combined sources	3
Helixⁱ	72 – 79	Combined sources	8
Helixⁱ	80 – 82	Combined sources	3
Helixⁱ	83 – 88	Combined sources	6
Helixⁱ	94 – 102	Combined sources	9
Beta strandⁱ	105 – 107	Combined sources	3
Beta strandⁱ	110 – 114	Combined sources	5
Helixⁱ	118 – 134	Combined sources	17
Helixⁱ	141 – 143	Combined sources	3
Helixⁱ	145 – 147	Combined sources	3
Beta strandⁱ	153 – 155	Combined sources	3
Turnⁱ	186 – 190	Combined sources	5
Beta strandⁱ	197 – 201	Combined sources	5
Beta strandⁱ	205 – 211	Combined sources	7
Helixⁱ	213 – 243	Combined sources	31
Helixⁱ	245 – 247	Combined sources	3
Helixⁱ	250 – 252	Combined sources	3
Helixⁱ	253 – 275	Combined sources	23
Helixⁱ	277 – 281	Combined sources	5
Beta strandⁱ	282 – 289	Combined sources	8
Helixⁱ	300 – 330	Combined sources	31
Helixⁱ	337 – 341	Combined sources	5
Helixⁱ	344 – 365	Combined sources	22
Beta strandⁱ	368 – 370	Combined sources	3
Turnⁱ	372 – 374	Combined sources	3
Beta strandⁱ	377 – 382	Combined sources	6
Helixⁱ	384 – 390	Combined sources	7
Helixⁱ	392 – 417	Combined sources	26
Helixⁱ	432 – 443	Combined sources	12
Helixⁱ	445 – 460	Combined sources	16
Helixⁱ	462 – 467	Combined sources	6
Helixⁱ	474 – 489	Combined sources	16
Helixⁱ	492 – 495	Combined sources	4
Helixⁱ	498 – 511	Combined sources	14

Show more details

3D structure databases

AlphaFoldDBⁱ	Q9ULV1
SMRⁱ	Q9ULV1
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	40 – 161	FZPROSITE-ProRule annotationAdd BLAST		122

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	499 – 504	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity		6
Motifⁱ	535 – 537	PDZ-binding		3

Domainⁱ

Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain 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

Sequence similaritiesⁱ

Belongs to the G-protein coupled receptor Fz/Smo family.Curated

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG3577, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000157141
HOGENOMⁱ	CLU_007873_2_1_1
InParanoidⁱ	Q9ULV1
OMAⁱ	HWGEFRA
Database of Orthologous Groups More...OrthoDBⁱ	509772at2759
PhylomeDBⁱ	Q9ULV1
TreeFamⁱ	TF317907

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd07448, CRD_FZ4, 1 hit
Gene3Dⁱ	1.10.2000.10, 1 hit
InterProⁱ	View protein in InterPro IPR015526, Frizzled/SFRP IPR000539, Frizzled/Smoothened_TM IPR020067, Frizzled_dom IPR036790, Frizzled_dom_sf IPR041765, FZ4_CRD IPR026551, FZD4 IPR017981, GPCR_2-like
PANTHERⁱ	PTHR11309, PTHR11309, 1 hit PTHR11309:SF23, PTHR11309:SF23, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01534, Frizzled, 1 hit PF01392, Fz, 1 hit
PRINTSⁱ	PR00489, FRIZZLED
SMARTⁱ	View protein in SMART SM00063, FRI, 1 hit SM01330, Frizzled, 1 hit
SUPFAMⁱ	SSF63501, SSF63501, 1 hit
PROSITEⁱ	View protein in PROSITE PS50038, FZ, 1 hit PS50261, G_PROTEIN_RECEP_F2_4, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

Q9ULV1-1 [UniParc]FASTA Add to basket

« Hide

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

Length:537

Mass (Da):59,881

Last modified:March 29, 2005 - v2

Checksum:ⁱE0A83ECEC560A381

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	481	I → T in BAA86286 (PubMed:10544037).Curated		1
Sequence conflictⁱ	500	T → S in BAA86286 (PubMed:10544037).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_063920	33	P → S in EVR1; benign variant. 3 PublicationsCorresponds to variant dbSNP:rs61735304EnsemblClinVar.	1
Natural variantⁱVAR_063921	36	G → D in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358281Ensembl.	1
Natural variantⁱVAR_063922	40	E → Q in EVR1. 1 PublicationCorresponds to variant dbSNP:rs139401671EnsemblClinVar.	1
Natural variantⁱVAR_063923	69	H → Y in EVR1; minor reduction of its wild-type activity. 4 PublicationsCorresponds to variant dbSNP:rs80358282EnsemblClinVar.	1
Natural variantⁱVAR_063924	105	M → T in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358285Ensembl.	1
Natural variantⁱVAR_038947	105	M → V in EVR1; loss of function. 4 PublicationsCorresponds to variant dbSNP:rs80358284EnsemblClinVar.	1
Natural variantⁱVAR_063925	114	I → T in EVR1. 1 Publication	1
Natural variantⁱVAR_038948	157	M → V in EVR1; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs80358286Ensembl.	1
Natural variantⁱVAR_063926	168	P → S3 PublicationsCorresponds to variant dbSNP:rs61735303EnsemblClinVar.	1
Natural variantⁱVAR_063927	181	C → R in EVR1; increased signaling activity. 2 PublicationsCorresponds to variant dbSNP:rs80358287Ensembl.	1
Natural variantⁱVAR_063928	203	K → N in retinopathy of prematurity. 1 PublicationCorresponds to variant dbSNP:rs1476724511Ensembl.	1
Natural variantⁱVAR_063929	204	C → R in EVR1; reduced signaling activity in presence of WNT3A but no change in presence of NDP/norrin. 2 PublicationsCorresponds to variant dbSNP:rs80358288Ensembl.	1
Natural variantⁱVAR_063930	204	C → Y in EVR1. 1 PublicationCorresponds to variant dbSNP:rs1064794064EnsemblClinVar.	1
Natural variantⁱVAR_063931	223	M → K in EVR1. 1 Publication	1
Natural variantⁱVAR_063932	256	I → V in EVR1. 1 PublicationCorresponds to variant dbSNP:rs104894223EnsemblClinVar.	1
Natural variantⁱVAR_063933	335	W → C in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358292EnsemblClinVar.	1
Natural variantⁱVAR_063934	342	M → V in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358293EnsemblClinVar.	1
Natural variantⁱVAR_063935	370	A → G in retinopathy of prematurity. 1 Publication	1
Natural variantⁱVAR_063936	417	R → Q in EVR1; 48% loss of its wild-type activity; associated in a EVR4 patient with mutation CYS-444 in LPR5. 3 PublicationsCorresponds to variant dbSNP:rs80358294EnsemblClinVar.	1
Natural variantⁱVAR_036413	436	K → T in a colorectal cancer sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_063937	445	T → P in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358297Ensembl.	1
Natural variantⁱVAR_063938	488	G → D in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358298Ensembl.	1
Natural variantⁱVAR_017777	493 – 494	Missing in EVR1; loss of function. 3 Publications	2
Natural variantⁱVAR_063939	497	S → F in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358300Ensembl.	1
Natural variantⁱVAR_063940	525	G → R in EVR1. 1 Publication	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8279.1
PIRⁱ	JC7127
NCBI Reference Sequences More...RefSeqⁱ	NP_036325.2, NM_012193.3

Genome annotation databases

Ensemblⁱ	ENST00000531380.2; ENSP00000434034.1; ENSG00000174804.4
GeneIDⁱ	8322
KEGGⁱ	hsa:8322
MANE-Selectⁱ	ENST00000531380.2; ENSP00000434034.1; NM_012193.4; NP_036325.2
UCSC genome browser More...UCSCⁱ	uc001pce.4, human

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9ULV1	Frizzled-4		RAT		538	UniRef90_Q9ULV1
Frizzled-4		MOUSE		537
Frizzled-4		VULVU		669
Frizzled-4		RHIRO		486
Frizzled-4		THEGE		486
+225

Protein	Similar proteins		Species	Score	Length	Source
Q9ULV1	Frizzled-4		RAT		538	UniRef50_Q9ULV1
Frizzled-4		MOUSE		537
Frizzled-4		CHICK		525
Frizzled-4		XENLA		523
Frizzled-4		VULVU		669
+679

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS8279.1
PIRⁱ	JC7127
RefSeqⁱ	NP_036325.2, NM_012193.3

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	5BPB	X-ray	2.20	A/B/C/D	42-179	[»]
	5BPQ	X-ray	2.40	A/B/C/D	42-179	[»]
	5BQC	X-ray	3.00	B	42-179	[»]
	5BQE	X-ray	2.30	C	42-179	[»]
	5CL1	X-ray	3.80	C/D	38-160	[»]
	5CM4	X-ray	2.40	A/B	40-164	[»]
	5UWG	X-ray	2.56	A/B	40-164	[»]
	6BD4	X-ray	2.40	A	178-517	[»]
	6NE1	X-ray	3.01	A	42-161	[»]
AlphaFoldDBⁱ	Q9ULV1
SMRⁱ	Q9ULV1
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	113918, 20 interactors
CORUMⁱ	Q9ULV1
IntActⁱ	Q9ULV1, 13 interactors
MINTⁱ	Q9ULV1
STRINGⁱ	9606.ENSP00000434034

Chemistry databases

ChEMBLⁱ	CHEMBL4523491
GuidetoPHARMACOLOGYⁱ	232

Protein family/group databases

GPCRDBⁱ	Search...

GPCRDBⁱ

Search...

PTM databases

GlyConnectⁱ	2003, 5 N-Linked glycans (1 site)
GlyGenⁱ	Q9ULV1, 2 sites, 5 N-linked glycans (1 site)
iPTMnetⁱ	Q9ULV1
PhosphoSitePlusⁱ	Q9ULV1

Genetic variation databases

BioMutaⁱ	FZD4
DMDMⁱ	62298045

Proteomic databases

jPOSTⁱ	Q9ULV1
MassIVEⁱ	Q9ULV1
MaxQBⁱ	Q9ULV1
PaxDbⁱ	Q9ULV1
PeptideAtlasⁱ	Q9ULV1
PRIDEⁱ	Q9ULV1
ProteomicsDBⁱ	85129

Protocols and materials databases

ABCDⁱ	Q9ULV1, 21 sequenced antibodies
Antibodypediaⁱ	17696, 541 antibodies from 39 providers
The DNASU plasmid repository More...DNASUⁱ	8322

Genome annotation databases

Ensemblⁱ	ENST00000531380.2; ENSP00000434034.1; ENSG00000174804.4
GeneIDⁱ	8322
KEGGⁱ	hsa:8322
MANE-Selectⁱ	ENST00000531380.2; ENSP00000434034.1; NM_012193.4; NP_036325.2
UCSCⁱ	uc001pce.4, human

Organism-specific databases

CTDⁱ	8322
DisGeNETⁱ	8322
GeneCardsⁱ	FZD4
HGNCⁱ	HGNC:4042, FZD4
HPAⁱ	ENSG00000174804, Tissue enhanced (adipose)
MalaCardsⁱ	FZD4
MIMⁱ	133780, phenotype 604579, gene
neXtProtⁱ	NX_Q9ULV1
OpenTargetsⁱ	ENSG00000174804
Orphanetⁱ	891, Familial exudative vitreoretinopathy 91495, Persistent hyperplastic primary vitreous 90050, Retinopathy of prematurity
PharmGKBⁱ	PA28459
VEuPathDBⁱ	HostDB:ENSG00000174804
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3577, Eukaryota
GeneTreeⁱ	ENSGT00940000157141
HOGENOMⁱ	CLU_007873_2_1_1
InParanoidⁱ	Q9ULV1
OMAⁱ	HWGEFRA
OrthoDBⁱ	509772at2759
PhylomeDBⁱ	Q9ULV1
TreeFamⁱ	TF317907

Enzyme and pathway databases

PathwayCommonsⁱ	Q9ULV1
Reactomeⁱ	R-HSA-373080, Class B/2 (Secretin family receptors) R-HSA-4086398, Ca2+ pathway R-HSA-4608870, Asymmetric localization of PCP proteins R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-5099900, WNT5A-dependent internalization of FZD4 R-HSA-5340588, Signaling by RNF43 mutants R-HSA-8856825, Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828, Clathrin-mediated endocytosis
SignaLinkⁱ	Q9ULV1
SIGNORⁱ	Q9ULV1

Miscellaneous databases

BioGRID-ORCSⁱ	8322, 12 hits in 1080 CRISPR screens
ChiTaRSⁱ	FZD4, human
GeneWikiⁱ	FZD4
GenomeRNAiⁱ	8322
Pharosⁱ	Q9ULV1, Tchem
Protein Ontology More...PROⁱ	PR:Q9ULV1
RNActⁱ	Q9ULV1, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000174804, Expressed in right lung and 221 other tissues
Genevisibleⁱ	Q9ULV1, HS

Family and domain databases

CDDⁱ	cd07448, CRD_FZ4, 1 hit
Gene3Dⁱ	1.10.2000.10, 1 hit
InterProⁱ	View protein in InterPro IPR015526, Frizzled/SFRP IPR000539, Frizzled/Smoothened_TM IPR020067, Frizzled_dom IPR036790, Frizzled_dom_sf IPR041765, FZ4_CRD IPR026551, FZD4 IPR017981, GPCR_2-like
PANTHERⁱ	PTHR11309, PTHR11309, 1 hit PTHR11309:SF23, PTHR11309:SF23, 1 hit
Pfamⁱ	View protein in Pfam PF01534, Frizzled, 1 hit PF01392, Fz, 1 hit
PRINTSⁱ	PR00489, FRIZZLED
SMARTⁱ	View protein in SMART SM00063, FRI, 1 hit SM01330, Frizzled, 1 hit
SUPFAMⁱ	SSF63501, SSF63501, 1 hit
PROSITEⁱ	View protein in PROSITE PS50038, FZ, 1 hit PS50261, G_PROTEIN_RECEP_F2_4, 1 hit
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	FZD4_HUMAN
Accessionⁱ	Q9ULV1Primary (citable) accession number: Q9ULV1 Secondary accession number(s): A8K9Q3, Q14C97, Q6S9E4
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
	Last sequence update:	March 29, 2005
	Last modified:	May 25, 2022
	This is version 199 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Reference proteome

Documents

7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries
Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries
Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

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UniProtKB - Q9ULV1 (FZD4_HUMAN)

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Frizzled-4

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Q9ULV1

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