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Q14332 (FZD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-2

Short name=Fz-2
Short name=hFz2
Alternative name(s):
FzE2
Gene names
Name:FZD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length565 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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.

Subcellular location

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

Tissue specificity

Widely expressed. In the adult, mainly found in heart, placenta, skeletal muscle, lung, kidney, pancreas, prostate, testis, ovary and colon. In the fetus, expressed in brain, lung and kidney. Low levels in fetal liver.

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
   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

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

cell-cell signaling

Inferred from electronic annotation. Source: Ensembl

cochlea morphogenesis

Inferred from electronic annotation. Source: Ensembl

epithelial cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hard palate development

Inferred from electronic annotation. Source: Ensembl

inner ear receptor cell development

Inferred from electronic annotation. Source: Ensembl

membranous septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

muscular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

planar cell polarity pathway involved in neural tube closure

Inferred from electronic annotation. Source: Ensembl

positive regulation of cGMP metabolic process

Inferred from mutant phenotype PubMed 19946729. Source: BHF-UCL

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 18929644. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18215320PubMed 18929644. Source: BHF-UCL

sensory perception of smell

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

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

cytoplasm

Inferred from direct assay PubMed 19038973. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 18929644. 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 Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 565542Frizzled-2
PRO_0000012978

Regions

Topological domain24 – 247224Extracellular Potential
Transmembrane248 – 26821Helical; Name=1; Potential
Topological domain269 – 27911Cytoplasmic Potential
Transmembrane280 – 30021Helical; Name=2; Potential
Topological domain301 – 32727Extracellular Potential
Transmembrane328 – 34821Helical; Name=3; Potential
Topological domain349 – 37022Cytoplasmic Potential
Transmembrane371 – 39121Helical; Name=4; Potential
Topological domain392 – 41423Extracellular Potential
Transmembrane415 – 43521Helical; Name=5; Potential
Topological domain436 – 46126Cytoplasmic Potential
Transmembrane462 – 48221Helical; Name=6; Potential
Topological domain483 – 51937Extracellular Potential
Transmembrane520 – 54021Helical; Name=7; Potential
Topological domain541 – 56525Cytoplasmic Potential
Domain34 – 153120FZ
Motif543 – 5486Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif563 – 5653PDZ-binding
Compositional bias181 – 1877Poly-Gly

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1541N-linked (GlcNAc...) Potential
Disulfide bond39 ↔ 100 By similarity
Disulfide bond47 ↔ 93 By similarity
Disulfide bond84 ↔ 121 By similarity
Disulfide bond110 ↔ 150 By similarity
Disulfide bond114 ↔ 138 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q14332 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: AA387876A1DDE063

FASTA56563,554
        10         20         30         40         50         60 
MRPRSALPRL LLPLLLLPAA GPAQFHGEKG ISIPDHGFCQ PISIPLCTDI AYNQTIMPNL 

        70         80         90        100        110        120 
LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC TVLEQAIPPC RSICERARQG 

       130        140        150        160        170        180 
CEALMNKFGF QWPERLRCEH FPRHGAEQIC VGQNHSEDGA PALLTTAPPP GLQPGAGGTP 

       190        200        210        220        230        240 
GGPGGGGAPP RYATLEHPFH CPRVLKVPSY LSYKFLGERD CAAPCEPARP DGSMFFSQEE 

       250        260        270        280        290        300 
TRFARLWILT WSVLCCASTF FTVTTYLVDM QRFRYPERPI IFLSGCYTMV SVAYIAGFVL 

       310        320        330        340        350        360 
QERVVCNERF SEDGYRTVVQ GTKKEGCTIL FMMLYFFSMA SSIWWVILSL TWFLAAGMKW 

       370        380        390        400        410        420 
GHEAIEANSQ YFHLAAWAVP AVKTITILAM GQIDGDLLSG VCFVGLNSLD PLRGFVLAPL 

       430        440        450        460        470        480 
FVYLFIGTSF LLAGFVSLFR IRTIMKHDGT KTEKLERLMV RIGVFSVLYT VPATIVIACY 

       490        500        510        520        530        540 
FYEQAFREHW ERSWVSQHCK SLAIPCPAHY TPRMSPDFTV YMIKYLMTLI VGITSGFWIW 

       550        560 
SGKTLHSWRK FYTRLTNSRH GETTV 

« Hide

References

« Hide 'large scale' references
[1]"A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1."
Zhao Z., Lee C.C., Baldini A., Caskey C.T.
Genomics 27:370-373(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Ovary.
[2]"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.
[3]"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].
[4]"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] OF 282-343.
Tissue: Esophageal carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L37882 mRNA. Translation: AAB46397.1.
AB017364 mRNA. Translation: BAA34667.1.
BC113402 mRNA. Translation: AAI13403.1.
BC113404 mRNA. Translation: AAI13405.1.
CCDSCCDS11484.1.
PIRJE0338.
RefSeqNP_001457.1. NM_001466.3.
UniGeneHs.142912.
Hs.732654.

3D structure databases

ProteinModelPortalQ14332.
SMRQ14332. Positions 39-145, 191-556.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108811. 4 interactions.
IntActQ14332. 1 interaction.
STRING9606.ENSP00000323901.

Chemistry

GuidetoPHARMACOLOGY230.

Protein family/group databases

MEROPSI93.001.
GPCRDBSearch...

PTM databases

PhosphoSiteQ14332.

Polymorphism databases

DMDM17433019.

Proteomic databases

MaxQBQ14332.
PaxDbQ14332.
PRIDEQ14332.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315323; ENSP00000323901; ENSG00000180340.
GeneID2535.
KEGGhsa:2535.
UCSCuc002igx.2. human.

Organism-specific databases

CTD2535.
GeneCardsGC17P042645.
HGNCHGNC:4040. FZD2.
HPAHPA057667.
MIM600667. gene.
neXtProtNX_Q14332.
PharmGKBPA28457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOVERGENHBG006977.
InParanoidQ14332.
KOK02235.
OMACENFPRH.
OrthoDBEOG7M3J01.
PhylomeDBQ14332.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ14332.
BgeeQ14332.
CleanExHS_FZD2.
GenevestigatorQ14332.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 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

ChiTaRSFZD2. human.
GeneWikiFZD2.
GenomeRNAi2535.
NextBio10005.
PROQ14332.
SOURCESearch...

Entry information

Entry nameFZD2_HUMAN
AccessionPrimary (citable) accession number: Q14332
Secondary accession number(s): Q0VG82
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 130 of the entry and version 1 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 chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries