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UniProtKB - Q9ULV1 (FZD4_HUMAN)

Entry version 189 (22 Apr 2020)
Sequence version 2 (29 Mar 2005)
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Protein

Frizzled-4

Gene

FZD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processWnt signaling pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...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 RNF mutants show enhanced WNT signaling and proliferation
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q9ULV1

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q9ULV1

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Frizzled-4
Short name:
Fz-4
Short name:
hFz4
Alternative name(s):
FzE4
CD_antigen: CD344
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:FZD4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:4042 FZD4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		604579 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9ULV1

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini37 – 212Extracellular1 PublicationAdd BLAST176
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei213 – 243Helical; Name=11 PublicationAdd BLAST31
Topological domaini244 – 249Cytoplasmic1 Publication6
Transmembranei250 – 275Helical; Name=21 PublicationAdd BLAST26
Topological domaini276 – 299Extracellular1 PublicationAdd BLAST24
Transmembranei300 – 333Helical; Name=31 PublicationAdd BLAST34
Topological domaini334 – 336Cytoplasmic1 Publication3
Transmembranei337 – 365Helical; Name=41 PublicationAdd BLAST29
Topological domaini366 – 383Extracellular1 PublicationAdd BLAST18
Transmembranei384 – 418Helical; Name=51 PublicationAdd BLAST35
Topological domaini419 – 431Cytoplasmic1 PublicationAdd BLAST13
Transmembranei432 – 460Helical; Name=61 PublicationAdd BLAST29
Topological domaini461 – 473Extracellular1 PublicationAdd BLAST13
Transmembranei474 – 495Helical; Name=71 PublicationAdd BLAST22
Topological domaini496 – 537Cytoplasmic1 PublicationAdd BLAST42

Keywords - Cellular componenti

Cell membrane, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Vitreoretinopathy, exudative 1 (EVR1)13 Publications
The disease is caused by mutations 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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06392033P → S in EVR1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs61735304EnsemblClinVar.1
Natural variantiVAR_06392136G → D in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358281Ensembl.1
Natural variantiVAR_06392240E → Q in EVR1. 1 PublicationCorresponds to variant dbSNP:rs139401671EnsemblClinVar.1
Natural variantiVAR_06392369H → Y in EVR1; minor reduction of its wild-type activity. 4 PublicationsCorresponds to variant dbSNP:rs80358282EnsemblClinVar.1
Natural variantiVAR_063924105M → T in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358285Ensembl.1
Natural variantiVAR_038947105M → V in EVR1; loss of function. 4 PublicationsCorresponds to variant dbSNP:rs80358284EnsemblClinVar.1
Natural variantiVAR_063925114I → T in EVR1. 1 Publication1
Natural variantiVAR_038948157M → V in EVR1; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs80358286Ensembl.1
Natural variantiVAR_063927181C → R in EVR1; increased signaling activity. 2 PublicationsCorresponds to variant dbSNP:rs80358287Ensembl.1
Natural variantiVAR_063929204C → 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_063930204C → Y in EVR1. 1 PublicationCorresponds to variant dbSNP:rs1064794064EnsemblClinVar.1
Natural variantiVAR_063931223M → K in EVR1. 1 Publication1
Natural variantiVAR_063932256I → V in EVR1. 1 PublicationCorresponds to variant dbSNP:rs104894223EnsemblClinVar.1
Natural variantiVAR_063933335W → C in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358292EnsemblClinVar.1
Natural variantiVAR_063934342M → V in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358293EnsemblClinVar.1
Natural variantiVAR_063936417R → 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_063937445T → P in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358297Ensembl.1
Natural variantiVAR_063938488G → D in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358298Ensembl.1
Natural variantiVAR_017777493 – 494Missing in EVR1; loss of function. 3 Publications2
Natural variantiVAR_063939497S → F in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358300Ensembl.1
Natural variantiVAR_063940525G → R in EVR1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi233S → A: Increased signaling activity in presence of NDP/norrin but not in presence of WNT3A. 1 Publication1
Mutagenesisi233S → F: Slightly increased signaling activity in presence of NDP/norrin and reduced signaling in presence of WNT3A. 1 Publication1
Mutagenesisi250Y → F: Reduced signaling activity in presence of NDP/norrin. 1 Publication1
Mutagenesisi250Y → F: Reduced signaling activity. 1 Publication1
Mutagenesisi253R → C: Reduced signaling activity in presence of NDP/norrin. 1 Publication1
Mutagenesisi265Y → A: Slight increase in signaling activity. 1 Publication1
Mutagenesisi269Y → A: Increased signaling activity. 1 Publication1
Mutagenesisi341E → A: Reduced signaling activity in presence of NDP/norrin. 1 Publication1
Mutagenesisi371D → A: No effect on signaling activity. 1 Publication1
Mutagenesisi378Y → A: Increased signaling activity. 1 Publication1
Mutagenesisi381N → A: Slight increase in signaling activity. 1 Publication1
Mutagenesisi399L → F: No effect on signaling activity. 1 Publication1
Mutagenesisi418S → N: Increased signaling activity. 1 Publication1
Mutagenesisi444Y → A or F: Reduced signaling activity. 1 Publication1
Mutagenesisi455Y → A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin. 1 Publication1
Mutagenesisi458E → A: No effect on signaling activity. 1 Publication1
Mutagenesisi477E → A: Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin. 1 Publication1
Mutagenesisi480K → A: Increased signaling activity. 1 Publication1
Mutagenesisi494W → L: Reduced signaling activity. 1 Publication1
Mutagenesisi496W → A: Reduced signaling activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		8322

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		FZD4

MalaCards human disease database

More...MalaCardsi		FZD4
MIMi133780 phenotype

Open Targets

More...OpenTargetsi		ENSG00000174804

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		891 Familial exudative vitreoretinopathy
91495 Persistent hyperplastic primary vitreous
90050 Retinopathy of prematurity

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA28459

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9ULV1 Tbio

Chemistry databases

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		232

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		FZD4

Domain mapping of disease mutations (DMDM)

More...DMDMi		62298045

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 36Sequence analysisAdd BLAST36
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001298537 – 537Frizzled-4Add BLAST501

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi45 ↔ 106PROSITE-ProRule annotation
Disulfide bondi53 ↔ 99PROSITE-ProRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi59N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi90 ↔ 128PROSITE-ProRule annotation
Disulfide bondi117 ↔ 158PROSITE-ProRule annotation
Disulfide bondi121 ↔ 145PROSITE-ProRule annotation
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi181 ↔ 2001 Publication
Disulfide bondi204 ↔ 2821 Publication
Disulfide bondi302 ↔ 3771 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9ULV1

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9ULV1

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9ULV1

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9ULV1

PeptideAtlas

More...PeptideAtlasi		Q9ULV1

PRoteomics IDEntifications database

More...PRIDEi		Q9ULV1

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		85129

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		2003

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9ULV1

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9ULV1

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000174804 Expressed in adipose tissue of abdominal region and 212 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9ULV1 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000174804 Tissue enhanced (adipose)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with MAGI3 and NDP.

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

Interacts (via FZ domain) with TSKU.

Interacts with glypican GPC3 (PubMed:24496449).

By similarity1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Show more details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		113918, 12 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q9ULV1

Protein interaction database and analysis system

More...IntActi		Q9ULV1, 7 interactors

Molecular INTeraction database

More...MINTi		Q9ULV1

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000434034

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9ULV1 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1537
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9ULV1

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini40 – 161FZPROSITE-ProRule annotationAdd BLAST122

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi499 – 504Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi535 – 537PDZ-binding3

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3577 Eukaryota
ENOG410XRC8 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000157141

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_007873_2_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9ULV1

KEGG Orthology (KO)

More...KOi		K02354

Identification of Orthologs from Complete Genome Data

More...OMAi		IRIAMCQ

Database of Orthologous Groups

More...OrthoDBi		509772at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9ULV1

TreeFam database of animal gene trees

More...TreeFami		TF317907

Family and domain databases

Conserved Domains Database

More...CDDi		cd07448 CRD_FZ4, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.2000.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...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

The PANTHER Classification System

More...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

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00489 FRIZZLED

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF63501 SSF63501, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50038 FZ, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

Q9ULV1-1 [UniParc]FASTAAdd 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iE0A83ECEC560A381
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti481I → T in BAA86286 (PubMed:10544037).Curated1
Sequence conflicti500T → S in BAA86286 (PubMed:10544037).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06392033P → S in EVR1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs61735304EnsemblClinVar.1
Natural variantiVAR_06392136G → D in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358281Ensembl.1
Natural variantiVAR_06392240E → Q in EVR1. 1 PublicationCorresponds to variant dbSNP:rs139401671EnsemblClinVar.1
Natural variantiVAR_06392369H → Y in EVR1; minor reduction of its wild-type activity. 4 PublicationsCorresponds to variant dbSNP:rs80358282EnsemblClinVar.1
Natural variantiVAR_063924105M → T in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358285Ensembl.1
Natural variantiVAR_038947105M → V in EVR1; loss of function. 4 PublicationsCorresponds to variant dbSNP:rs80358284EnsemblClinVar.1
Natural variantiVAR_063925114I → T in EVR1. 1 Publication1
Natural variantiVAR_038948157M → V in EVR1; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs80358286Ensembl.1
Natural variantiVAR_063926168P → S3 PublicationsCorresponds to variant dbSNP:rs61735303EnsemblClinVar.1
Natural variantiVAR_063927181C → R in EVR1; increased signaling activity. 2 PublicationsCorresponds to variant dbSNP:rs80358287Ensembl.1
Natural variantiVAR_063928203K → N in retinopathy of prematurity. 1 PublicationCorresponds to variant dbSNP:rs1476724511Ensembl.1
Natural variantiVAR_063929204C → 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_063930204C → Y in EVR1. 1 PublicationCorresponds to variant dbSNP:rs1064794064EnsemblClinVar.1
Natural variantiVAR_063931223M → K in EVR1. 1 Publication1
Natural variantiVAR_063932256I → V in EVR1. 1 PublicationCorresponds to variant dbSNP:rs104894223EnsemblClinVar.1
Natural variantiVAR_063933335W → C in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358292EnsemblClinVar.1
Natural variantiVAR_063934342M → V in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358293EnsemblClinVar.1
Natural variantiVAR_063935370A → G in retinopathy of prematurity. 1 Publication1
Natural variantiVAR_063936417R → 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_036413436K → T in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_063937445T → P in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358297Ensembl.1
Natural variantiVAR_063938488G → D in EVR1. 2 PublicationsCorresponds to variant dbSNP:rs80358298Ensembl.1
Natural variantiVAR_017777493 – 494Missing in EVR1; loss of function. 3 Publications2
Natural variantiVAR_063939497S → F in EVR1. 1 PublicationCorresponds to variant dbSNP:rs80358300Ensembl.1
Natural variantiVAR_063940525G → R in EVR1. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

Protein sequence database of the Protein Information Resource

More...PIRi		JC7127

NCBI Reference Sequences

More...RefSeqi		NP_036325.2, NM_012193.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000531380; ENSP00000434034; ENSG00000174804

Database of genes from NCBI RefSeq genomes

More...GeneIDi		8322

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:8322

UCSC genome browser

More...UCSCi		uc001pce.4 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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
CCDSiCCDS8279.1
PIRiJC7127
RefSeqiNP_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 entryMethodResolution (Å)ChainPositionsPDBsum
5BPBX-ray2.20A/B/C/D42-179[»]
5BPQX-ray2.40A/B/C/D42-179[»]
5BQCX-ray3.00B42-179[»]
5BQEX-ray2.30C42-179[»]
5CL1X-ray3.80C/D38-160[»]
5CM4X-ray2.40A/B40-164[»]
5UWGX-ray2.56A/B40-164[»]
6BD4X-ray2.40A178-517[»]
6NE1X-ray3.01A42-161[»]
SMRiQ9ULV1
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi113918, 12 interactors
CORUMiQ9ULV1
IntActiQ9ULV1, 7 interactors
MINTiQ9ULV1
STRINGi9606.ENSP00000434034

Chemistry databases

GuidetoPHARMACOLOGYi232

Protein family/group databases

Information system for G protein-coupled receptors (GPCRs)

More...GPCRDBi		Search...

PTM databases

GlyConnecti2003
iPTMnetiQ9ULV1
PhosphoSitePlusiQ9ULV1

Polymorphism and mutation databases

BioMutaiFZD4
DMDMi62298045

Proteomic databases

jPOSTiQ9ULV1
MassIVEiQ9ULV1
MaxQBiQ9ULV1
PaxDbiQ9ULV1
PeptideAtlasiQ9ULV1
PRIDEiQ9ULV1
ProteomicsDBi85129

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		Q9ULV1

Antibodypedia a portal for validated antibodies

More...Antibodypediai		17696 501 antibodies

Genome annotation databases

EnsembliENST00000531380; ENSP00000434034; ENSG00000174804
GeneIDi8322
KEGGihsa:8322
UCSCiuc001pce.4 human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		8322
DisGeNETi8322

GeneCards: human genes, protein and diseases

More...GeneCardsi		FZD4
GeneReviewsiFZD4
HGNCiHGNC:4042 FZD4
HPAiENSG00000174804 Tissue enhanced (adipose)
MalaCardsiFZD4
MIMi133780 phenotype
604579 gene
neXtProtiNX_Q9ULV1
OpenTargetsiENSG00000174804
Orphaneti891 Familial exudative vitreoretinopathy
91495 Persistent hyperplastic primary vitreous
90050 Retinopathy of prematurity
PharmGKBiPA28459

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00940000157141
HOGENOMiCLU_007873_2_1_1
InParanoidiQ9ULV1
KOiK02354
OMAiIRIAMCQ
OrthoDBi509772at2759
PhylomeDBiQ9ULV1
TreeFamiTF317907

Enzyme and pathway databases

ReactomeiR-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 RNF mutants show enhanced WNT signaling and proliferation
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiQ9ULV1
SIGNORiQ9ULV1

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		FZD4 human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		FZD4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		8322
PharosiQ9ULV1 Tbio

Protein Ontology

More...PROi		PR:Q9ULV1
RNActiQ9ULV1 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000174804 Expressed in adipose tissue of abdominal region and 212 other tissues
GenevisibleiQ9ULV1 HS

Family and domain databases

CDDicd07448 CRD_FZ4, 1 hit
Gene3Di1.10.2000.10, 1 hit
InterProiView 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
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF23 PTHR11309:SF23, 1 hit
PfamiView protein in Pfam
PF01534 Frizzled, 1 hit
PF01392 Fz, 1 hit
PRINTSiPR00489 FRIZZLED
SMARTiView protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit
SUPFAMiSSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiFZD4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9ULV1
Secondary accession number(s): A8K9Q3, Q14C97, Q6S9E4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 29, 2005
Last modified: April 22, 2020
This is version 189 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  3. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  8. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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