UniProtKB - Q9ULV1 (FZD4_HUMAN)
Frizzled-4
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 PublicationGO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- cytokine binding Source: BHF-UCL
- cytokine receptor activity Source: BHF-UCL
- G protein-coupled receptor activity Source: UniProtKB-KW
- PDZ domain binding Source: UniProtKB
- protein-containing complex binding Source: ARUK-UCL
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- signaling receptor activity Source: ARUK-UCL
- ubiquitin protein ligase binding Source: UniProtKB
- Wnt-activated receptor activity Source: WormBase
- Wnt-protein binding Source: GO_Central
GO - Biological processi
- canonical Wnt signaling pathway Source: UniProtKB
- cellular response to leukemia inhibitory factor Source: Ensembl
- cellular response to retinoic acid Source: UniProtKB
- cerebellum vasculature morphogenesis Source: Ensembl
- extracellular matrix-cell signaling Source: Ensembl
- locomotion involved in locomotory behavior Source: Ensembl
- negative regulation of canonical Wnt signaling pathway Source: GO_Central
- negative regulation of cell-substrate adhesion Source: BHF-UCL
- neuron differentiation Source: UniProtKB
- non-canonical Wnt signaling pathway Source: ARUK-UCL
- Norrin signaling pathway Source: BHF-UCL
- positive regulation of cell migration Source: ARUK-UCL
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of JUN kinase activity Source: Ensembl
- positive regulation of neuron projection arborization Source: ARUK-UCL
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- progesterone secretion Source: Ensembl
- regulation of vascular endothelial growth factor receptor signaling pathway Source: Ensembl
- retinal blood vessel morphogenesis Source: Ensembl
- retina vasculature morphogenesis in camera-type eye Source: BHF-UCL
- sensory perception of sound Source: Ensembl
- substrate adhesion-dependent cell spreading Source: Ensembl
- vasculogenesis Source: Ensembl
- Wnt signaling pathway Source: ARUK-UCL
- Wnt signaling pathway, calcium modulating pathway Source: BHF-UCL
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-4Short 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4042, FZD4 |
MIMi | 604579, gene |
neXtProti | NX_Q9ULV1 |
VEuPathDBi | HostDB:ENSG00000174804 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Extracellular region or secreted
- extracellular space Source: GO_Central
Plasma Membrane
- integral component of plasma membrane Source: BHF-UCL
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: BHF-UCL
- cell-cell junction Source: Ensembl
- clathrin-coated endocytic vesicle membrane Source: Reactome
- dendrite Source: ARUK-UCL
- glutamatergic synapse Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | 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, MembranePathology & Biotechi
Involvement in diseasei
Vitreoretinopathy, exudative 1 (EVR1)13 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | 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 | Graphical view | 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 variantOrganism-specific databases
DisGeNETi | 8322 |
MalaCardsi | FZD4 |
MIMi | 133780, phenotype |
OpenTargetsi | ENSG00000174804 |
Orphaneti | 891, Familial exudative vitreoretinopathy 91495, Persistent hyperplastic primary vitreous 90050, Retinopathy of prematurity |
PharmGKBi | PA28459 |
Miscellaneous databases
Pharosi | Q9ULV1, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4523491 |
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 | Graphical view | 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 conjugationProteomic databases
jPOSTi | Q9ULV1 |
MassIVEi | Q9ULV1 |
MaxQBi | Q9ULV1 |
PaxDbi | Q9ULV1 |
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
Gene expression databases
Bgeei | ENSG00000174804, Expressed in right lung and 221 other tissues |
Genevisiblei | Q9ULV1, HS |
Organism-specific databases
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 PublicationBinary interactionsi
Q9ULV1
GO - Molecular functioni
- cytokine binding Source: BHF-UCL
- PDZ domain binding Source: UniProtKB
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- ubiquitin protein ligase binding Source: UniProtKB
- Wnt-protein binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 113918, 20 interactors |
CORUMi | Q9ULV1 |
IntActi | Q9ULV1, 13 interactors |
MINTi | Q9ULV1 |
STRINGi | 9606.ENSP00000434034 |
Miscellaneous databases
RNActi | Q9ULV1, protein |
Structurei
Secondary structure
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
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3577, Eukaryota |
GeneTreei | ENSGT00940000157141 |
HOGENOMi | CLU_007873_2_1_1 |
InParanoidi | Q9ULV1 |
OMAi | HWGEFRA |
OrthoDBi | 509772at2759 |
PhylomeDBi | Q9ULV1 |
TreeFami | TF317907 |
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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
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 | Graphical view | 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 |
CCDSi | CCDS8279.1 |
PIRi | JC7127 |
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 |
UCSCi | uc001pce.4, human |
Similar proteinsi
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: PDBei RCSB PDBi 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... |
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 |
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 |
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 |
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 proteomeDocuments
- 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