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O00144 (FZD9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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-9

Short name=Fz-9
Short name=hFz9
Alternative name(s):
FzE6
CD_antigen=CD349
Gene names
Name:FZD9
Synonyms:FZD3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length591 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

Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Expressed predominantly in adult and fetal brain, testis, eye, skeletal muscle and kidney. Moderately expressed in pancreas, thyroid, adrenal cortex, small intestine and stomach. Detected in fetal liver and kidney.

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.

Caution

Has been first described as FZD3 in literature.

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_processB cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

learning or memory

Inferred from electronic annotation. Source: Ensembl

neuroblast proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcell surface

Inferred from direct assay PubMed 20458727. Source: BHF-UCL

filopodium membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement Ref.1. Source: ProtInc

perinuclear region of cytoplasm

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 Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 591569Frizzled-9
PRO_0000013003

Regions

Topological domain23 – 229207Extracellular Potential
Transmembrane230 – 25021Helical; Name=1; Potential
Topological domain251 – 26616Cytoplasmic Potential
Transmembrane267 – 28721Helical; Name=2; Potential
Topological domain288 – 31528Extracellular Potential
Transmembrane316 – 33621Helical; Name=3; Potential
Topological domain337 – 35519Cytoplasmic Potential
Transmembrane356 – 37621Helical; Name=4; Potential
Topological domain377 – 40024Extracellular Potential
Transmembrane401 – 42121Helical; Name=5; Potential
Topological domain422 – 44726Cytoplasmic Potential
Transmembrane448 – 46821Helical; Name=6; Potential
Topological domain469 – 50840Extracellular Potential
Transmembrane509 – 52921Helical; Name=7; Potential
Topological domain530 – 59162Cytoplasmic Potential
Domain34 – 155122FZ
Motif532 – 5376Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1581N-linked (GlcNAc...) Potential
Disulfide bond39 ↔ 100 By similarity
Disulfide bond47 ↔ 93 By similarity
Disulfide bond84 ↔ 122 By similarity
Disulfide bond111 ↔ 152 By similarity
Disulfide bond115 ↔ 139 By similarity

Sequences

Sequence LengthMass (Da)Tools
O00144 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 0D3784A78DF0B2E5

FASTA59164,466
        10         20         30         40         50         60 
MAVAPLRGAL LLWQLLAAGG AALEIGRFDP ERGRGAAPCQ AVEIPMCRGI GYNLTRMPNL 

        70         80         90        100        110        120 
LGHTSQGEAA AELAEFAPLV QYGCHSHLRF FLCSLYAPMC TDQVSTPIPA CRPMCEQARL 

       130        140        150        160        170        180 
RCAPIMEQFN FGWPDSLDCA RLPTRNDPHA LCMEAPENAT AGPAEPHKGL GMLPVAPRPA 

       190        200        210        220        230        240 
RPPGDLGPGA GGSGTCENPE KFQYVEKSRS CAPRCGPGVE VFWSRRDKDF ALVWMAVWSA 

       250        260        270        280        290        300 
LCFFSTAFTV LTFLLEPHRF QYPERPIIFL SMCYNVYSLA FLIRAVAGAQ SVACDQEAGA 

       310        320        330        340        350        360 
LYVIQEGLEN TGCTLVFLLL YYFGMASSLW WVVLTLTWFL AAGKKWGHEA IEAHGSYFHM 

       370        380        390        400        410        420 
AAWGLPALKT IVILTLRKVA GDELTGLCYV ASTDAAALTG FVLVPLSGYL VLGSSFLLTG 

       430        440        450        460        470        480 
FVALFHIRKI MKTGGTNTEK LEKLMVKIGV FSILYTVPAT CVIVCYVYER LNMDFWRLRA 

       490        500        510        520        530        540 
TEQPCAAAAG PGGRRDCSLP GGSVPTVAVF MLKIFMSLVV GITSGVWVWS SKTFQTWQSL 

       550        560        570        580        590 
CYRKIAAGRA RAKACRAPGS YGRGTHCHYK APTVVLHMTK TDPSLENPTH L 

« Hide

References

« Hide 'large scale' references
[1]"A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23."
Wang Y.-K., Samos H.C., Peoples R., Perez-Jurado L.A., Nusse R., Francke U.
Hum. Mol. Genet. 6:465-472(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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 OF 269-329.
Tissue: Esophageal carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U82169 mRNA. Translation: AAC51174.1.
AC005049 Genomic DNA. Translation: AAQ93359.1.
RefSeqNP_003499.1. NM_003508.2.
UniGeneHs.647029.

3D structure databases

ProteinModelPortalO00144.
SMRO00144. Positions 39-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113922. 1 interaction.
MINTMINT-1477946.
STRING9606.ENSP00000345785.

Protein family/group databases

MEROPSI93.001.
GPCRDBSearch...

PTM databases

PhosphoSiteO00144.

Proteomic databases

PaxDbO00144.
PRIDEO00144.

Protocols and materials databases

DNASU8326.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344575; ENSP00000345785; ENSG00000188763.
ENST00000576173; ENSP00000461417; ENSG00000263254.
GeneID8326.
KEGGhsa:8326.
UCSCuc003tyb.3. human.

Organism-specific databases

CTD8326.
GeneCardsGC07P072848.
HGNCHGNC:4047. FZD9.
MIM601766. gene.
neXtProtNX_O00144.
PharmGKBPA28464.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidO00144.
KOK02842.
OMANALCMEA.
OrthoDBEOG7M3J01.
PhylomeDBO00144.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkO00144.

Gene expression databases

BgeeO00144.
CleanExHS_FZD3.
HS_FZD9.
GenevestigatorO00144.

Family and domain databases

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

GeneWikiFZD9.
GenomeRNAi8326.
NextBio31179.
PROO00144.
SOURCESearch...

Entry information

Entry nameFZD9_HUMAN
AccessionPrimary (citable) accession number: O00144
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: July 1, 1997
Last modified: February 19, 2014
This is version 124 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 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries