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Protein

Frizzled-7

Gene

FZD7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. 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.

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: UniProtKB
  • Wnt-activated receptor activity Source: ParkinsonsUK-UCL
  • Wnt-protein binding Source: BHF-UCL

GO - Biological processi

  • canonical Wnt signaling pathway Source: UniProtKB
  • cellular response to retinoic acid Source: UniProtKB
  • mesenchymal to epithelial transition Source: BHF-UCL
  • negative regulation of cell-substrate adhesion Source: BHF-UCL
  • negative regulation of ectodermal cell fate specification Source: BHF-UCL
  • neuron differentiation Source: UniProtKB
  • non-canonical Wnt signaling pathway via JNK cascade Source: BHF-UCL
  • positive regulation of epithelial cell proliferation involved in wound healing Source: BHF-UCL
  • positive regulation of JNK cascade Source: BHF-UCL
  • positive regulation of phosphorylation Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • regulation of catenin import into nucleus Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: BHF-UCL
  • skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: Ensembl
  • somatic stem cell division Source: Ensembl
  • stem cell population maintenance Source: BHF-UCL
  • substrate adhesion-dependent cell spreading Source: Ensembl
  • T cell differentiation in thymus Source: Ensembl
  • Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155760-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-4086400. PCP/CE pathway.
R-HSA-4608870. Asymmetric localization of PCP proteins.
SignaLinkiO75084.
SIGNORiO75084.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-7
Short name:
Fz-7
Short name:
hFz7
Alternative name(s):
FzE3
Gene namesi
Name:FZD7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:4045. FZD7.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 256ExtracellularSequence analysisAdd BLAST224
Transmembranei257 – 277Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini278 – 288CytoplasmicSequence analysisAdd BLAST11
Transmembranei289 – 309Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini310 – 336ExtracellularSequence analysisAdd BLAST27
Transmembranei337 – 357Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini358 – 379CytoplasmicSequence analysisAdd BLAST22
Transmembranei380 – 400Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini401 – 423ExtracellularSequence analysisAdd BLAST23
Transmembranei424 – 444Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini445 – 470CytoplasmicSequence analysisAdd BLAST26
Transmembranei471 – 491Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini492 – 528ExtracellularSequence analysisAdd BLAST37
Transmembranei529 – 549Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini550 – 574CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • integral component of membrane Source: BHF-UCL
  • plasma membrane Source: LIFEdb
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8324.
OpenTargetsiENSG00000155760.
PharmGKBiPA28462.

Chemistry databases

ChEMBLiCHEMBL3559688.

Polymorphism and mutation databases

BioMutaiFZD7.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000001299633 – 574Frizzled-7Add BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 110PROSITE-ProRule annotation
Disulfide bondi57 ↔ 103PROSITE-ProRule annotation
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi94 ↔ 131PROSITE-ProRule annotation
Disulfide bondi120 ↔ 160PROSITE-ProRule annotation
Disulfide bondi124 ↔ 148PROSITE-ProRule annotation
Glycosylationi164N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

MaxQBiO75084.
PaxDbiO75084.
PeptideAtlasiO75084.
PRIDEiO75084.

PTM databases

iPTMnetiO75084.
PhosphoSitePlusiO75084.

Expressioni

Tissue specificityi

High expression in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. Specifically expressed in squamous cell esophageal carcinomas.

Gene expression databases

BgeeiENSG00000155760.
CleanExiHS_FZD7.
GenevisibleiO75084. HS.

Interactioni

Subunit structurei

Interacts with MAGI3 and DVL1 (By similarity). Interacts with MYOC.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
SDCBPO005604EBI-746917,EBI-727004
UBQLN1Q9UMX03EBI-746917,EBI-741480
WNT3P567033EBI-746917,EBI-3644922

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • Wnt-protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113920. 10 interactors.
IntActiO75084. 9 interactors.
MINTiMINT-1461434.
STRINGi9606.ENSP00000286201.

Structurei

Secondary structure

1574
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi572 – 574Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4Z33X-ray2.45C/D569-574[»]
ProteinModelPortaliO75084.
SMRiO75084.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 163FZPROSITE-ProRule annotationAdd BLAST120

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi552 – 557Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi572 – 574PDZ-binding3

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.By similarity
The FZ domain is involved in binding with Wnt ligands.By similarity

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiO75084.
KOiK02432.
OMAiCVERFSE.
OrthoDBiEOG091G0N5M.
PhylomeDBiO75084.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026552. FZD7.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF31. PTHR11309:SF31. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O75084-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRDPGAAAPL SSLGLCALVL ALLGALSAGA GAQPYHGEKG ISVPDHGFCQ
60 70 80 90 100
PISIPLCTDI AYNQTILPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF
110 120 130 140 150
FLCSMYAPVC TVLDQAIPPC RSLCERARQG CEALMNKFGF QWPERLRCEN
160 170 180 190 200
FPVHGAGEIC VGQNTSDGSG GPGGGPTAYP TAPYLPDLPF TALPPGASDG
210 220 230 240 250
RGRPAFPFSC PRQLKVPPYL GYRFLGERDC GAPCEPGRAN GLMYFKEEER
260 270 280 290 300
RFARLWVGVW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYFMVA
310 320 330 340 350
VAHVAGFLLE DRAVCVERFS DDGYRTVAQG TKKEGCTILF MVLYFFGMAS
360 370 380 390 400
SIWWVILSLT WFLAAGMKWG HEAIEANSQY FHLAAWAVPA VKTITILAMG
410 420 430 440 450
QVDGDLLSGV CYVGLSSVDA LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI
460 470 480 490 500
RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV PATIVLACYF YEQAFREHWE
510 520 530 540 550
RTWLLQTCKS YAVPCPPGHF PPMSPDFTVF MIKYLMTMIV GITTGFWIWS
560 570
GKTLQSWRRF YHRLSHSSKG ETAV
Length:574
Mass (Da):63,620
Last modified:September 27, 2004 - v2
Checksum:i801934246B426DF5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8A → V in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti15L → F in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti201R → K in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti308L → F in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti408S → N in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti415L → F in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti433L → F in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti447L → F in BAA32424 (PubMed:9707618).Curated1
Sequence conflicti534Y → C in BAA32424 (PubMed:9707618).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04929224G → D.Corresponds to variant rs35111363dbSNPEnsembl.1
Natural variantiVAR_03302424G → S.1 PublicationCorresponds to variant rs755615030dbSNPEnsembl.1
Natural variantiVAR_033941196G → E.Corresponds to variant rs34908164dbSNPEnsembl.1
Natural variantiVAR_033942487A → V.Corresponds to variant rs35600847dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB010881 mRNA. Translation: BAA32424.1.
AB017365 mRNA. Translation: BAA34668.1.
AC069148 Genomic DNA. Translation: AAX93250.1.
CH471063 Genomic DNA. Translation: EAW70298.1.
BC015915 mRNA. Translation: AAH15915.1.
CCDSiCCDS2351.1.
PIRiJE0339.
RefSeqiNP_003498.1. NM_003507.1.
UniGeneiHs.173859.

Genome annotation databases

EnsembliENST00000286201; ENSP00000286201; ENSG00000155760.
GeneIDi8324.
KEGGihsa:8324.
UCSCiuc002uyw.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB010881 mRNA. Translation: BAA32424.1.
AB017365 mRNA. Translation: BAA34668.1.
AC069148 Genomic DNA. Translation: AAX93250.1.
CH471063 Genomic DNA. Translation: EAW70298.1.
BC015915 mRNA. Translation: AAH15915.1.
CCDSiCCDS2351.1.
PIRiJE0339.
RefSeqiNP_003498.1. NM_003507.1.
UniGeneiHs.173859.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4Z33X-ray2.45C/D569-574[»]
ProteinModelPortaliO75084.
SMRiO75084.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113920. 10 interactors.
IntActiO75084. 9 interactors.
MINTiMINT-1461434.
STRINGi9606.ENSP00000286201.

Chemistry databases

ChEMBLiCHEMBL3559688.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO75084.
PhosphoSitePlusiO75084.

Polymorphism and mutation databases

BioMutaiFZD7.

Proteomic databases

MaxQBiO75084.
PaxDbiO75084.
PeptideAtlasiO75084.
PRIDEiO75084.

Protocols and materials databases

DNASUi8324.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286201; ENSP00000286201; ENSG00000155760.
GeneIDi8324.
KEGGihsa:8324.
UCSCiuc002uyw.2. human.

Organism-specific databases

CTDi8324.
DisGeNETi8324.
GeneCardsiFZD7.
HGNCiHGNC:4045. FZD7.
MIMi603410. gene.
neXtProtiNX_O75084.
OpenTargetsiENSG00000155760.
PharmGKBiPA28462.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiO75084.
KOiK02432.
OMAiCVERFSE.
OrthoDBiEOG091G0N5M.
PhylomeDBiO75084.
TreeFamiTF317907.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155760-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-4086400. PCP/CE pathway.
R-HSA-4608870. Asymmetric localization of PCP proteins.
SignaLinkiO75084.
SIGNORiO75084.

Miscellaneous databases

ChiTaRSiFZD7. human.
GeneWikiiFZD7.
GenomeRNAii8324.
PROiO75084.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155760.
CleanExiHS_FZD7.
GenevisibleiO75084. HS.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026552. FZD7.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF31. PTHR11309:SF31. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFZD7_HUMAN
AccessioniPrimary (citable) accession number: O75084
Secondary accession number(s): O94816, Q53S59, Q96B74
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: September 27, 2004
Last modified: November 30, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.