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O75084 (FZD7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-7

Short name=Fz-7
Short name=hFz7
Alternative name(s):
FzE3
Gene names
Name:FZD7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length574 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with MAGI3 and DVL1 By similarity. Interacts with MYOC. Ref.6

Subcellular location

Membrane; Multi-pass membrane protein By similarity. Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

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.

Domain

Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman 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.

Post-translational modification

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

Sequence similarities

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

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger

Inferred from Biological aspect of Ancestor. Source: RefGenome

T cell differentiation in thymus

Inferred from electronic annotation. Source: Ensembl

Wnt signaling pathway, calcium modulating pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay PubMed 20802536. Source: UniProtKB

cellular response to retinoic acid

Inferred from sequence or structural similarity. Source: UniProtKB

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

mesenchymal to epithelial transition

Inferred from mutant phenotype PubMed 17016432. Source: BHF-UCL

negative regulation of cell-substrate adhesion

Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL

negative regulation of ectodermal cell fate specification

Inferred from mutant phenotype PubMed 18681827. Source: BHF-UCL

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

non-canonical Wnt signaling pathway via JNK cascade

Inferred from mutant phenotype PubMed 19773752. Source: BHF-UCL

positive regulation of JNK cascade

Inferred by curator PubMed 18256285. Source: BHF-UCL

positive regulation of epithelial cell proliferation involved in wound healing

Inferred from mutant phenotype PubMed 18313787. Source: BHF-UCL

positive regulation of phosphorylation

Inferred from direct assay PubMed 18256285. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18215320. Source: BHF-UCL

regulation of catenin import into nucleus

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 18681827. Source: BHF-UCL

satellite cell maintenance involved in skeletal muscle regeneration

Inferred from electronic annotation. Source: Ensembl

somatic stem cell division

Inferred from electronic annotation. Source: Ensembl

stem cell maintenance

Inferred from mutant phenotype PubMed 18681827. Source: BHF-UCL

substrate adhesion-dependent cell spreading

Inferred from electronic annotation. Source: Ensembl

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentapical part of cell

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement Ref.1. Source: BHF-UCL

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 18256285. Source: BHF-UCL

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction PubMed 19388021. Source: UniProtKB

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from physical interaction PubMed 18313787. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 574542Frizzled-7
PRO_0000012996

Regions

Topological domain33 – 256224Extracellular Potential
Transmembrane257 – 27721Helical; Name=1; Potential
Topological domain278 – 28811Cytoplasmic Potential
Transmembrane289 – 30921Helical; Name=2; Potential
Topological domain310 – 33627Extracellular Potential
Transmembrane337 – 35721Helical; Name=3; Potential
Topological domain358 – 37922Cytoplasmic Potential
Transmembrane380 – 40021Helical; Name=4; Potential
Topological domain401 – 42323Extracellular Potential
Transmembrane424 – 44421Helical; Name=5; Potential
Topological domain445 – 47026Cytoplasmic Potential
Transmembrane471 – 49121Helical; Name=6; Potential
Topological domain492 – 52837Extracellular Potential
Transmembrane529 – 54921Helical; Name=7; Potential
Topological domain550 – 57425Cytoplasmic Potential
Domain44 – 163120FZ
Motif552 – 5576Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif572 – 5743PDZ-binding

Amino acid modifications

Glycosylation631N-linked (GlcNAc...) Potential
Glycosylation1641N-linked (GlcNAc...) Potential
Disulfide bond49 ↔ 110 By similarity
Disulfide bond57 ↔ 103 By similarity
Disulfide bond94 ↔ 131 By similarity
Disulfide bond120 ↔ 160 By similarity
Disulfide bond124 ↔ 148 By similarity

Natural variations

Natural variant241G → D.
Corresponds to variant rs35111363 [ dbSNP | Ensembl ].
VAR_049292
Natural variant241G → S. Ref.7
VAR_033024
Natural variant1961G → E.
Corresponds to variant rs34908164 [ dbSNP | Ensembl ].
VAR_033941
Natural variant4871A → V.
Corresponds to variant rs35600847 [ dbSNP | Ensembl ].
VAR_033942

Experimental info

Sequence conflict81A → V in BAA32424. Ref.1
Sequence conflict151L → F in BAA32424. Ref.1
Sequence conflict2011R → K in BAA32424. Ref.1
Sequence conflict3081L → F in BAA32424. Ref.1
Sequence conflict4081S → N in BAA32424. Ref.1
Sequence conflict4151L → F in BAA32424. Ref.1
Sequence conflict4331L → F in BAA32424. Ref.1
Sequence conflict4471L → F in BAA32424. Ref.1
Sequence conflict5341Y → C in BAA32424. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O75084 [UniParc].

Last modified September 27, 2004. Version 2.
Checksum: 801934246B426DF5

FASTA57463,620
        10         20         30         40         50         60 
MRDPGAAAPL SSLGLCALVL ALLGALSAGA GAQPYHGEKG ISVPDHGFCQ PISIPLCTDI 

        70         80         90        100        110        120 
AYNQTILPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC TVLDQAIPPC 

       130        140        150        160        170        180 
RSLCERARQG CEALMNKFGF QWPERLRCEN FPVHGAGEIC VGQNTSDGSG GPGGGPTAYP 

       190        200        210        220        230        240 
TAPYLPDLPF TALPPGASDG RGRPAFPFSC PRQLKVPPYL GYRFLGERDC GAPCEPGRAN 

       250        260        270        280        290        300 
GLMYFKEEER RFARLWVGVW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYFMVA 

       310        320        330        340        350        360 
VAHVAGFLLE DRAVCVERFS DDGYRTVAQG TKKEGCTILF MVLYFFGMAS SIWWVILSLT 

       370        380        390        400        410        420 
WFLAAGMKWG HEAIEANSQY FHLAAWAVPA VKTITILAMG QVDGDLLSGV CYVGLSSVDA 

       430        440        450        460        470        480 
LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV 

       490        500        510        520        530        540 
PATIVLACYF YEQAFREHWE RTWLLQTCKS YAVPCPPGHF PPMSPDFTVF MIKYLMTMIV 

       550        560        570 
GITTGFWIWS GKTLQSWRRF YHRLSHSSKG ETAV 

« Hide

References

« Hide 'large scale' references
[1]"A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals."
Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.
Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], COUPLING TO BETA-CATENIN PATHWAY.
Tissue: Esophageal carcinoma.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7."
Sagara N., Toda G., Hirai M., Terada M., Katoh M.
Biochem. Biophys. Res. Commun. 252:117-122(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal lung.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Myocilin is a modulator of Wnt signaling."
Kwon H.S., Lee H.S., Ji Y., Rubin J.S., Tomarev S.I.
Mol. Cell. Biol. 29:2139-2154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOC.
[7]"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas."
Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L.
Breast Cancer Res. 9:R5-R5(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-24.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJE0339.
RefSeqNP_003498.1. NM_003507.1.
UniGeneHs.173859.

3D structure databases

ProteinModelPortalO75084.
SMRO75084. Positions 49-155, 203-564.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113920. 4 interactions.
IntActO75084. 6 interactions.
MINTMINT-1461434.
STRING9606.ENSP00000286201.

Protein family/group databases

MEROPSI93.001.
GPCRDBSearch...

PTM databases

PhosphoSiteO75084.

Proteomic databases

PaxDbO75084.
PRIDEO75084.

Protocols and materials databases

DNASU8324.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286201; ENSP00000286201; ENSG00000155760.
GeneID8324.
KEGGhsa:8324.
UCSCuc002uyw.1. human.

Organism-specific databases

CTD8324.
GeneCardsGC02P202863.
HGNCHGNC:4045. FZD7.
MIM603410. gene.
neXtProtNX_O75084.
PharmGKBPA28462.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233237.
HOVERGENHBG006977.
InParanoidO75084.
KOK02432.
OMACVERFSE.
OrthoDBEOG7M3J01.
PhylomeDBO75084.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkO75084.

Gene expression databases

BgeeO75084.
CleanExHS_FZD7.
GenevestigatorO75084.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026552. FZD7.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF31. PTHR11309:SF31. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFZD7. human.
GeneWikiFZD7.
GenomeRNAi8324.
NextBio31171.
PROO75084.
SOURCESearch...

Entry information

Entry nameFZD7_HUMAN
AccessionPrimary (citable) accession number: O75084
Secondary accession number(s): O94816, Q53S59, Q96B74
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: September 27, 2004
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries