Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9NPG1 (FZD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-3

Short name=Fz-3
Short name=hFz3
Gene names
Name:FZD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length666 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 VANGL2 By similarity.

Subcellular location

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

Tissue specificity

Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis.

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 diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
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

canonical Wnt signaling pathway

Inferred from direct assay PubMed 20802536. Source: UniProtKB

cell proliferation in midbrain

Inferred from Biological aspect of Ancestor. Source: RefGenome

commissural neuron axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

establishment of planar polarity

Inferred from Biological aspect of Ancestor. Source: RefGenome

facial nucleus development

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hair follicle development

Inferred from electronic annotation. Source: Ensembl

inner ear morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

neural tube closure

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from electronic annotation. Source: Ensembl

post-anal tail morphogenesis

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

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

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

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

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

presynaptic active zone

Inferred from Biological aspect of Ancestor. Source: RefGenome

   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 by curator PubMed 19038973. Source: BHF-UCL

Wnt-protein binding

Inferred from physical interaction PubMed 19038973. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19277043. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform Long (identifier: Q9NPG1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: Q9NPG1-2)

Also known as: FZD3deltaC;

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.5
Chain23 – 666644Frizzled-3
PRO_0000012982

Regions

Topological domain23 – 205183Extracellular Potential
Transmembrane206 – 22621Helical; Name=1; Potential
Topological domain227 – 23711Cytoplasmic Potential
Transmembrane238 – 25821Helical; Name=2; Potential
Topological domain259 – 28830Extracellular Potential
Transmembrane289 – 30921Helical; Name=3; Potential
Topological domain310 – 32819Cytoplasmic Potential
Transmembrane329 – 34921Helical; Name=4; Potential
Topological domain350 – 37425Extracellular Potential
Transmembrane375 – 39521Helical; Name=5; Potential
Topological domain396 – 42025Cytoplasmic Potential
Transmembrane421 – 44121Helical; Name=6; Potential
Topological domain442 – 47736Extracellular Potential
Transmembrane478 – 49821Helical; Name=7; Potential
Topological domain499 – 666168Cytoplasmic Potential
Domain23 – 136114FZ
Motif502 – 5076Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity

Amino acid modifications

Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation2651N-linked (GlcNAc...) Potential
Glycosylation3561N-linked (GlcNAc...) Potential
Disulfide bond28 ↔ 89 By similarity
Disulfide bond36 ↔ 82 By similarity
Disulfide bond73 ↔ 110 By similarity
Disulfide bond99 ↔ 133 By similarity
Disulfide bond103 ↔ 127 By similarity

Natural variations

Natural variant41T → S. Ref.6
Corresponds to variant rs140115204 [ dbSNP | Ensembl ].
VAR_066960
Natural variant1991L → M. Ref.6
VAR_066961
Natural variant5451I → V. Ref.6
VAR_066962

Experimental info

Sequence conflict1271C → R in BAF84169. Ref.4
Sequence conflict4021I → V in BAF84169. Ref.4
Sequence conflict6641T → A in BAF84169. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 46D7C46E21160215

FASTA66676,263
        10         20         30         40         50         60 
MAMTWIVFSL WPLTVFMGHI GGHSLFSCEP ITLRMCQDLP YNTTFMPNLL NHYDQQTAAL 

        70         80         90        100        110        120 
AMEPFHPMVN LDCSRDFRPF LCALYAPICM EYGRVTLPCR RLCQRAYSEC SKLMEMFGVP 

       130        140        150        160        170        180 
WPEDMECSRF PDCDEPYPRL VDLNLAGEPT EGAPVAVQRD YGFWCPRELK IDPDLGYSFL 

       190        200        210        220        230        240 
HVRDCSPPCP NMYFRREELS FARYFIGLIS IICLSATLFT FLTFLIDVTR FRYPERPIIF 

       250        260        270        280        290        300 
YAVCYMMVSL IFFIGFLLED RVACNASIPA QYKASTVTQG SHNKACTMLF MILYFFTMAG 

       310        320        330        340        350        360 
SVWWVILTIT WFLAAVPKWG SEAIEKKALL FHASAWGIPG TLTIILLAMN KIEGDNISGV 

       370        380        390        400        410        420 
CFVGLYDVDA LRYFVLAPLC LYVVVGVSLL LAGIISLNRV RIEIPLEKEN QDKLVKFMIR 

       430        440        450        460        470        480 
IGVFSILYLV PLLVVIGCYF YEQAYRGIWE TTWIQERCRE YHIPCPYQVT QMSRPDLILF 

       490        500        510        520        530        540 
LMKYLMALIV GIPSVFWVGS KKTCFEWASF FHGRRKKEIV NESRQVLQEP DFAQSLLRDP 

       550        560        570        580        590        600 
NTPIIRKSRG TSTQGTSTHA SSTQLAMVDD QRSKAGSIHS KVSSYHGSLH RSRDGRYTPC 

       610        620        630        640        650        660 
SYRGMEERLP HGSMSRLTDH SRHSSSHRLN EQSRHSSIRD LSNNPMTHIT HGTSMNRVIE 


EDGTSA 

« Hide

Isoform Short (FZD3deltaC) (Sequence not available).

References

« Hide 'large scale' references
[1]"Molecular cloning and genomic structure of human frizzled-3 at chromosome 8p21."
Kirikoshi H., Koike J., Sagara N., Saitoh T., Tokuhara M., Tanaka K., Sekihara H., Hirai M., Katoh M.
Biochem. Biophys. Res. Commun. 271:8-14(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"Identification, gene structure and expression of human frizzled-3 (FZD3)."
Sala C.F., Formenti E., Terstappen G.C., Caricasole A.
Biochem. Biophys. Res. Commun. 273:27-34(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[3]"Characterization of mouse frizzled-3 expression in hair follicle development and identification of the human homolog in keratinocytes."
Hung B.S., Wang X.-Q., Cam G.R., Rothnagel J.A.
J. Invest. Dermatol. 116:940-946(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Keratinocyte.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-37.
[6]"FZD6 is a novel gene for human neural tube defects."
De Marco P., Merello E., Rossi A., Piatelli G., Cama A., Kibar Z., Capra V.
Hum. Mutat. 33:384-390(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-4; MET-199 AND VAL-545.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB039723 mRNA. Translation: BAA94968.1.
AJ272427 mRNA. Translation: CAB89114.1.
AY005130 mRNA. Translation: AAF89088.1.
AK291480 mRNA. Translation: BAF84169.1.
CCDSCCDS6069.1. [Q9NPG1-1]
PIRJC7312.
RefSeqNP_059108.1. NM_017412.3. [Q9NPG1-1]
NP_665873.1. NM_145866.1. [Q9NPG1-1]
UniGeneHs.40735.
Hs.734277.

3D structure databases

ProteinModelPortalQ9NPG1.
SMRQ9NPG1. Positions 28-136, 182-507.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113689. 1 interaction.
IntActQ9NPG1. 1 interaction.
STRING9606.ENSP00000240093.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9NPG1.

Polymorphism databases

DMDM17433071.

Proteomic databases

MaxQBQ9NPG1.
PaxDbQ9NPG1.
PRIDEQ9NPG1.

Protocols and materials databases

DNASU7976.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000240093; ENSP00000240093; ENSG00000104290. [Q9NPG1-1]
ENST00000537916; ENSP00000437489; ENSG00000104290. [Q9NPG1-1]
GeneID7976.
KEGGhsa:7976.
UCSCuc003xgx.3. human. [Q9NPG1-1]

Organism-specific databases

CTD7976.
GeneCardsGC08P028351.
HGNCHGNC:4041. FZD3.
HPACAB024995.
HPA042320.
MIM606143. gene.
neXtProtNX_Q9NPG1.
PharmGKBPA28458.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259824.
HOGENOMHOG000233237.
HOVERGENHBG006977.
InParanoidQ9NPG1.
KOK02329.
OMAMSWIVFY.
OrthoDBEOG7M3J01.
PhylomeDBQ9NPG1.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9NPG1.

Gene expression databases

ArrayExpressQ9NPG1.
BgeeQ9NPG1.
CleanExHS_FZD3.
GenevestigatorQ9NPG1.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026553. FZD3_vertebrates.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF22. PTHR11309:SF22. 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

ChiTaRSFZD3. human.
GeneWikiFZD3.
GenomeRNAi7976.
NextBio30495.
PROQ9NPG1.
SOURCESearch...

Entry information

Entry nameFZD3_HUMAN
AccessionPrimary (citable) accession number: Q9NPG1
Secondary accession number(s): A8K615
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 123 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 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 8

Human chromosome 8: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries