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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

  1. frizzled binding Source: UniProtKB
  2. G-protein coupled receptor activity Source: GO_Central
  3. PDZ domain binding Source: UniProtKB
  4. Wnt-activated receptor activity Source: GO_Central
  5. Wnt-protein binding Source: BHF-UCL

GO - Biological processi

  1. canonical Wnt signaling pathway Source: UniProtKB
  2. cellular response to retinoic acid Source: UniProtKB
  3. mesenchymal to epithelial transition Source: BHF-UCL
  4. negative regulation of cell-substrate adhesion Source: BHF-UCL
  5. negative regulation of ectodermal cell fate specification Source: BHF-UCL
  6. neuron differentiation Source: UniProtKB
  7. non-canonical Wnt signaling pathway via JNK cascade Source: BHF-UCL
  8. positive regulation of epithelial cell proliferation involved in wound healing Source: BHF-UCL
  9. positive regulation of JNK cascade Source: BHF-UCL
  10. positive regulation of phosphorylation Source: BHF-UCL
  11. positive regulation of transcription, DNA-templated Source: BHF-UCL
  12. regulation of catenin import into nucleus Source: BHF-UCL
  13. regulation of transcription, DNA-templated Source: BHF-UCL
  14. skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: Ensembl
  15. somatic stem cell division Source: Ensembl
  16. stem cell maintenance Source: BHF-UCL
  17. substrate adhesion-dependent cell spreading Source: Ensembl
  18. T cell differentiation in thymus Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_172581. PCP/CE pathway.
REACT_172638. Asymmetric localization of PCP proteins.
REACT_18372. Class B/2 (Secretin family receptors).
SignaLinkiO75084.

Protein family/group databases

MEROPSiI93.001.

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
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:4045. FZD7.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 256224ExtracellularSequence AnalysisAdd
BLAST
Transmembranei257 – 27721Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini278 – 28811CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei289 – 30921Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini310 – 33627ExtracellularSequence AnalysisAdd
BLAST
Transmembranei337 – 35721Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini358 – 37922CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei380 – 40021Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini401 – 42323ExtracellularSequence AnalysisAdd
BLAST
Transmembranei424 – 44421Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini445 – 47026CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei471 – 49121Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini492 – 52837ExtracellularSequence AnalysisAdd
BLAST
Transmembranei529 – 54921Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini550 – 57425CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28462.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 574542Frizzled-7PRO_0000012996Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi49 ↔ 110PROSITE-ProRule annotation
Disulfide bondi57 ↔ 103PROSITE-ProRule annotation
Glycosylationi63 – 631N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi94 ↔ 131PROSITE-ProRule annotation
Disulfide bondi120 ↔ 160PROSITE-ProRule annotation
Disulfide bondi124 ↔ 148PROSITE-ProRule annotation
Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis

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.
PRIDEiO75084.

PTM databases

PhosphoSiteiO75084.

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

BgeeiO75084.
CleanExiHS_FZD7.
GenevestigatoriO75084.

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
WNT3P567033EBI-746917,EBI-3644922

Protein-protein interaction databases

BioGridi113920. 4 interactions.
IntActiO75084. 6 interactions.
MINTiMINT-1461434.
STRINGi9606.ENSP00000286201.

Structurei

3D structure databases

ProteinModelPortaliO75084.
SMRiO75084. Positions 49-155, 230-565.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 163120FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi552 – 5576Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi572 – 5743PDZ-binding

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiO75084.
KOiK02432.
OMAiCVERFSE.
OrthoDBiEOG7M3J01.
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.
[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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81A → V in BAA32424. (PubMed:9707618)Curated
Sequence conflicti15 – 151L → F in BAA32424. (PubMed:9707618)Curated
Sequence conflicti201 – 2011R → K in BAA32424. (PubMed:9707618)Curated
Sequence conflicti308 – 3081L → F in BAA32424. (PubMed:9707618)Curated
Sequence conflicti408 – 4081S → N in BAA32424. (PubMed:9707618)Curated
Sequence conflicti415 – 4151L → F in BAA32424. (PubMed:9707618)Curated
Sequence conflicti433 – 4331L → F in BAA32424. (PubMed:9707618)Curated
Sequence conflicti447 – 4471L → F in BAA32424. (PubMed:9707618)Curated
Sequence conflicti534 – 5341Y → C in BAA32424. (PubMed:9707618)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241G → D.
Corresponds to variant rs35111363 [ dbSNP | Ensembl ].
VAR_049292
Natural varianti24 – 241G → S.1 Publication
VAR_033024
Natural varianti196 – 1961G → E.
Corresponds to variant rs34908164 [ dbSNP | Ensembl ].
VAR_033941
Natural varianti487 – 4871A → V.
Corresponds to variant rs35600847 [ dbSNP | Ensembl ].
VAR_033942

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.1. 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

ProteinModelPortaliO75084.
SMRiO75084. Positions 49-155, 230-565.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113920. 4 interactions.
IntActiO75084. 6 interactions.
MINTiMINT-1461434.
STRINGi9606.ENSP00000286201.

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

PTM databases

PhosphoSiteiO75084.

Proteomic databases

MaxQBiO75084.
PaxDbiO75084.
PRIDEiO75084.

Protocols and materials databases

DNASUi8324.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286201; ENSP00000286201; ENSG00000155760.
GeneIDi8324.
KEGGihsa:8324.
UCSCiuc002uyw.1. human.

Organism-specific databases

CTDi8324.
GeneCardsiGC02P202863.
HGNCiHGNC:4045. FZD7.
MIMi603410. gene.
neXtProtiNX_O75084.
PharmGKBiPA28462.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiO75084.
KOiK02432.
OMAiCVERFSE.
OrthoDBiEOG7M3J01.
PhylomeDBiO75084.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_172581. PCP/CE pathway.
REACT_172638. Asymmetric localization of PCP proteins.
REACT_18372. Class B/2 (Secretin family receptors).
SignaLinkiO75084.

Miscellaneous databases

ChiTaRSiFZD7. human.
GeneWikiiFZD7.
GenomeRNAii8324.
NextBioi31171.
PROiO75084.
SOURCEiSearch...

Gene expression databases

BgeeiO75084.
CleanExiHS_FZD7.
GenevestigatoriO75084.

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.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

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: February 4, 2015
This is version 136 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

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.