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FZD4 frizzled class receptor 4 [ Homo sapiens (human) ]

Gene ID: 8322, updated on 4-Nov-2018

Summary

Official Symbol
FZD4provided by HGNC
Official Full Name
frizzled class receptor 4provided by HGNC
Primary source
HGNC:HGNC:4042
See related
Ensembl:ENSG00000174804 MIM:604579; Vega:OTTHUMG00000167231
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Fz4; EVR1; FEVR; Fz-4; FzE4; GPCR; hFz4; CD344; FZD4S
Summary
This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]
Expression
Broad expression in fat (RPKM 98.6), kidney (RPKM 18.6) and 14 other tissues See more
Orthologs

Genomic context

See FZD4 in Genome Data Viewer
Location:
11q14.2
Exon count:
2
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (86945675..86955398, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (86656717..86666440, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene serine protease 23 Neighboring gene uncharacterized LOC107984429 Neighboring gene uncharacterized LOC107984428 Neighboring gene uncharacterized LOC100506368 Neighboring gene uncharacterized LOC105369422 Neighboring gene heterogeneous nuclear ribonucleoprotein C pseudogene 8

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2012-07-06)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-06)

ClinGen Genome Curation PagePubMed

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of frizzled family receptor 4 (FZD4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Association Between Physico-Chemical Features and Toxicity Associated Pathways, organism-specific biosystem (from WikiPathways)
    Association Between Physico-Chemical Features and Toxicity Associated Pathways, organism-specific biosystemThis pathway is based on Figure 8 of "Mapping drug physico-chemical features to pathway activity reveals molecular networks linked to toxicity outcome."(See bibliography). These 3 pathways demonstr...
  • Asymmetric localization of PCP proteins, organism-specific biosystem (from REACTOME)
    Asymmetric localization of PCP proteins, organism-specific biosystemOne of the hallmarks of the Planar Cell Polarity pathway is the asymmetric distribution of proteins on opposite membranes of a single cell. In Drosophila, Stbm and Pk (homologues to the human VANGL1/...
  • Basal cell carcinoma, organism-specific biosystem (from KEGG)
    Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
  • Basal cell carcinoma, conserved biosystem (from KEGG)
    Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
  • Beta-catenin independent WNT signaling, organism-specific biosystem (from REACTOME)
    Beta-catenin independent WNT signaling, organism-specific biosystemHumans and mice have 19 identified WNT proteins that were originally classified as either 'canonical' or 'non-canonical' depending upon whether they were able to transform the mouse mammary epithelia...
  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Ca2+ pathway, organism-specific biosystem (from REACTOME)
    Ca2+ pathway, organism-specific biosystemA number of so called non-canonical WNT ligands have been shown to promote intracellular calcium release upon FZD binding. This beta-catenin-independent WNT pathway acts through heterotrimeric G pro...
  • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
  • Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
    Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
  • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • Ectoderm Differentiation, organism-specific biosystem (from WikiPathways)
    Ectoderm Differentiation, organism-specific biosystemModel depicting ectoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • HTLV-I infection, organism-specific biosystem (from KEGG)
    HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • HTLV-I infection, conserved biosystem (from KEGG)
    HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • Hippo signaling pathway, organism-specific biosystem (from KEGG)
    Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • Hippo signaling pathway, conserved biosystem (from KEGG)
    Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • Melanogenesis, organism-specific biosystem (from KEGG)
    Melanogenesis, organism-specific biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
  • Melanogenesis, conserved biosystem (from KEGG)
    Melanogenesis, conserved biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Mesodermal Commitment Pathway, organism-specific biosystem (from WikiPathways)
    Mesodermal Commitment Pathway, organism-specific biosystemModel depicting mesodermal specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell l...
  • PCP/CE pathway, organism-specific biosystem (from REACTOME)
    PCP/CE pathway, organism-specific biosystemThe planar cell polarity (PCP) pathway controls the establishment of polarity within the plane of a sheet of cells. PCP was initially characterized in Drosophila, where it controls the arrangement o...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • RNF mutants show enhanced WNT signaling and proliferation, organism-specific biosystem (from REACTOME)
    RNF mutants show enhanced WNT signaling and proliferation, organism-specific biosystemRNF43 and related protein ZNRF3 are E3 ubiquitin ligases that negatively regulate WNT signaling by downregulating FZD receptors at the cell surface (Mukai et al, 2010; Hao et al, 2012). Frameshift l...
  • Regulation of FZD by ubiquitination, organism-specific biosystem (from REACTOME)
    Regulation of FZD by ubiquitination, organism-specific biosystemWNT responsiveness is influenced by expression levels of FZD and LRP proteins. Levels of these receptors at the cell surface are regulated in part by endocytosis, but the mechanisms are not fully el...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Signaling by WNT in cancer, organism-specific biosystem (from REACTOME)
    Signaling by WNT in cancer, organism-specific biosystemThe WNT signaling pathway has been linked with cancer ever since the identification of the first WNT as a gene activated by integration of mouse mammary tumor virus proviral DNA in virally-induced br...
  • Signaling by Wnt, organism-specific biosystem (from REACTOME)
    Signaling by Wnt, organism-specific biosystemWNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Sai...
  • Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
    TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
  • WNT5A-dependent internalization of FZD4, organism-specific biosystem (from REACTOME)
    WNT5A-dependent internalization of FZD4, organism-specific biosystemWNT5A induces internalization of FZD4 in a manner that depends upon PKC-mediated phosphorylation of DVL2. Uptake of FZD4 appears to occur in a clathrin, AP-2 and ARBB2-dependent mannner (Chen et al,...
  • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
    Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell plurip...
  • Wnt signaling, organism-specific biosystem (from KEGG)
    Wnt signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • Wnt signaling, conserved biosystem (from KEGG)
    Wnt signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • Wnt signaling network, organism-specific biosystem (from Pathway Interaction Database)
    Wnt signaling network, organism-specific biosystem
    Wnt signaling network
  • Wnt signaling pathway, organism-specific biosystem (from KEGG)
    Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • Wnt signaling pathway, conserved biosystem (from KEGG)
    Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • mTOR signaling pathway, organism-specific biosystem (from KEGG)
    mTOR signaling pathway, organism-specific biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
  • mTOR signaling pathway, conserved biosystem (from KEGG)
    mTOR signaling pathway, conserved biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC34390

Gene Ontology Provided by GOA

Function Evidence Code Pubs
G protein-coupled receptor activity IEA
Inferred from Electronic Annotation
more info
 
PDZ domain binding IDA
Inferred from Direct Assay
more info
PubMed 
PDZ domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
Wnt-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Wnt-activated receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
Wnt-protein binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Wnt-protein binding TAS
Traceable Author Statement
more info
PubMed 
amyloid-beta binding IPI
Inferred from Physical Interaction
more info
PubMed 
cytokine binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
Wnt signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
Wnt signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
Wnt signaling pathway, calcium modulating pathway IDA
Inferred from Direct Assay
more info
PubMed 
Wnt signaling pathway, calcium modulating pathway TAS
Traceable Author Statement
more info
 
Wnt signaling pathway, planar cell polarity pathway TAS
Traceable Author Statement
more info
 
canonical Wnt signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
canonical Wnt signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
canonical Wnt signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
 
cellular response to retinoic acid ISS
Inferred from Sequence or Structural Similarity
more info
 
cerebellum vasculature morphogenesis IEA
Inferred from Electronic Annotation
more info
 
extracellular matrix-cell signaling IEA
Inferred from Electronic Annotation
more info
 
locomotion involved in locomotory behavior IEA
Inferred from Electronic Annotation
more info
 
membrane organization TAS
Traceable Author Statement
more info
 
negative regulation of cell-substrate adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
neuron differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
non-canonical Wnt signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
non-canonical Wnt signaling pathway TAS
Traceable Author Statement
more info
PubMed 
positive regulation of DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of JUN kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of neuron projection arborization ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
progesterone secretion IEA
Inferred from Electronic Annotation
more info
 
regulation of vascular endothelial growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
retina vasculature morphogenesis in camera-type eye IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
retina vasculature morphogenesis in camera-type eye IMP
Inferred from Mutant Phenotype
more info
PubMed 
retinal blood vessel morphogenesis IEA
Inferred from Electronic Annotation
more info
 
sensory perception of sound IEA
Inferred from Electronic Annotation
more info
 
substrate adhesion-dependent cell spreading IEA
Inferred from Electronic Annotation
more info
 
vasculogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cell-cell junction IEA
Inferred from Electronic Annotation
more info
 
clathrin-coated endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
clathrin-coated vesicle membrane TAS
Traceable Author Statement
more info
 
dendrite ISS
Inferred from Sequence or Structural Similarity
more info
 
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane IC
Inferred by Curator
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
frizzled-4
Names
WNT receptor frizzled-4
frizzled 4, seven transmembrane spanning receptor
frizzled family receptor 4
frizzled homolog 4

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011752.1 RefSeqGene

    Range
    4994..14717
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_012193.3NP_036325.2  frizzled-4 precursor

    See identical proteins and their annotated locations for NP_036325.2

    Status: REVIEWED

    Source sequence(s)
    AK292768, AP001528, BC114527
    Consensus CDS
    CCDS8279.1
    UniProtKB/Swiss-Prot
    Q9ULV1
    Related
    ENSP00000434034.1, OTTHUMP00000235516, ENST00000531380.1, OTTHUMT00000393818
    Conserved Domains (2) summary
    cd07448
    Location:42167
    CRD_FZ4; Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor
    cd15038
    Location:209509
    7tmF_FZD4; class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    86945675..86955398 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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