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Protein

Frizzled-9

Gene

FZD9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. G-protein coupled receptor activity Source: GO_Central
  2. protein heterodimerization activity Source: BHF-UCL
  3. protein homodimerization activity Source: BHF-UCL
  4. Wnt-activated receptor activity Source: ProtInc
  5. Wnt-protein binding Source: UniProtKB

GO - Biological processi

  1. B cell differentiation Source: Ensembl
  2. canonical Wnt signaling pathway Source: GO_Central
  3. learning or memory Source: Ensembl
  4. nervous system development Source: ProtInc
  5. neuroblast proliferation Source: Ensembl
  6. non-canonical Wnt signaling pathway Source: GO_Central
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_18372. Class B/2 (Secretin family receptors).
SignaLinkiO00144.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-9
Short name:
Fz-9
Short name:
hFz9
Alternative name(s):
FzE6
CD_antigen: CD349
Gene namesi
Name:FZD9
Synonyms:FZD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:4047. FZD9.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 229207ExtracellularSequence AnalysisAdd
BLAST
Transmembranei230 – 25021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini251 – 26616CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei267 – 28721Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini288 – 31528ExtracellularSequence AnalysisAdd
BLAST
Transmembranei316 – 33621Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini337 – 35519CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei356 – 37621Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini377 – 40024ExtracellularSequence AnalysisAdd
BLAST
Transmembranei401 – 42121Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini422 – 44726CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei448 – 46821Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini469 – 50840ExtracellularSequence AnalysisAdd
BLAST
Transmembranei509 – 52921Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini530 – 59162CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. cytoplasm Source: BHF-UCL
  3. filopodium membrane Source: Ensembl
  4. integral component of membrane Source: ProtInc
  5. perinuclear region of cytoplasm Source: Ensembl
  6. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28464.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Chaini23 – 591569Frizzled-9PRO_0000013003Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi39 ↔ 100PROSITE-ProRule annotation
Disulfide bondi47 ↔ 93PROSITE-ProRule annotation
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi84 ↔ 122PROSITE-ProRule annotation
Disulfide bondi111 ↔ 152PROSITE-ProRule annotation
Disulfide bondi115 ↔ 139PROSITE-ProRule annotation
Glycosylationi158 – 1581N-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

PaxDbiO00144.
PRIDEiO00144.

PTM databases

PhosphoSiteiO00144.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO00144.
CleanExiHS_FZD3.
HS_FZD9.
GenevestigatoriO00144.

Interactioni

Protein-protein interaction databases

BioGridi113922. 3 interactions.
MINTiMINT-1477946.
STRINGi9606.ENSP00000345785.

Structurei

3D structure databases

ProteinModelPortaliO00144.
SMRiO00144. Positions 39-155, 234-428.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 155122FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi532 – 5376Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity

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.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiO00144.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG7M3J01.
PhylomeDBiO00144.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 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.

O00144-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAVAPLRGAL LLWQLLAAGG AALEIGRFDP ERGRGAAPCQ AVEIPMCRGI
60 70 80 90 100
GYNLTRMPNL LGHTSQGEAA AELAEFAPLV QYGCHSHLRF FLCSLYAPMC
110 120 130 140 150
TDQVSTPIPA CRPMCEQARL RCAPIMEQFN FGWPDSLDCA RLPTRNDPHA
160 170 180 190 200
LCMEAPENAT AGPAEPHKGL GMLPVAPRPA RPPGDLGPGA GGSGTCENPE
210 220 230 240 250
KFQYVEKSRS CAPRCGPGVE VFWSRRDKDF ALVWMAVWSA LCFFSTAFTV
260 270 280 290 300
LTFLLEPHRF QYPERPIIFL SMCYNVYSLA FLIRAVAGAQ SVACDQEAGA
310 320 330 340 350
LYVIQEGLEN TGCTLVFLLL YYFGMASSLW WVVLTLTWFL AAGKKWGHEA
360 370 380 390 400
IEAHGSYFHM AAWGLPALKT IVILTLRKVA GDELTGLCYV ASTDAAALTG
410 420 430 440 450
FVLVPLSGYL VLGSSFLLTG FVALFHIRKI MKTGGTNTEK LEKLMVKIGV
460 470 480 490 500
FSILYTVPAT CVIVCYVYER LNMDFWRLRA TEQPCAAAAG PGGRRDCSLP
510 520 530 540 550
GGSVPTVAVF MLKIFMSLVV GITSGVWVWS SKTFQTWQSL CYRKIAAGRA
560 570 580 590
RAKACRAPGS YGRGTHCHYK APTVVLHMTK TDPSLENPTH L
Length:591
Mass (Da):64,466
Last modified:July 1, 1997 - v1
Checksum:i0D3784A78DF0B2E5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82169 mRNA. Translation: AAC51174.1.
AC005049 Genomic DNA. Translation: AAQ93359.1.
CCDSiCCDS5548.1.
RefSeqiNP_003499.1. NM_003508.2.
UniGeneiHs.647029.

Genome annotation databases

EnsembliENST00000344575; ENSP00000345785; ENSG00000188763.
GeneIDi8326.
KEGGihsa:8326.
UCSCiuc003tyb.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82169 mRNA. Translation: AAC51174.1.
AC005049 Genomic DNA. Translation: AAQ93359.1.
CCDSiCCDS5548.1.
RefSeqiNP_003499.1. NM_003508.2.
UniGeneiHs.647029.

3D structure databases

ProteinModelPortaliO00144.
SMRiO00144. Positions 39-155, 234-428.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113922. 3 interactions.
MINTiMINT-1477946.
STRINGi9606.ENSP00000345785.

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

PTM databases

PhosphoSiteiO00144.

Proteomic databases

PaxDbiO00144.
PRIDEiO00144.

Protocols and materials databases

DNASUi8326.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344575; ENSP00000345785; ENSG00000188763.
GeneIDi8326.
KEGGihsa:8326.
UCSCiuc003tyb.3. human.

Organism-specific databases

CTDi8326.
GeneCardsiGC07P072848.
HGNCiHGNC:4047. FZD9.
MIMi601766. gene.
neXtProtiNX_O00144.
PharmGKBiPA28464.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiO00144.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG7M3J01.
PhylomeDBiO00144.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
SignaLinkiO00144.

Miscellaneous databases

GeneWikiiFZD9.
GenomeRNAii8326.
NextBioi31179.
PROiO00144.
SOURCEiSearch...

Gene expression databases

BgeeiO00144.
CleanExiHS_FZD3.
HS_FZD9.
GenevestigatoriO00144.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 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 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.
    , 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.

Entry informationi

Entry nameiFZD9_HUMAN
AccessioniPrimary (citable) accession number: O00144
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: July 1, 1997
Last modified: February 4, 2015
This is version 131 of the entry and version 1 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

Caution

Has been first described as FZD3 in literature.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.