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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 WNT2 that is 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 (By similarity). Plays a role in neuromuscular junction (NMJ) assembly by negatively regulating the clustering of acetylcholine receptors (AChR) through the beta-catenin canonical signaling pathway (By similarity). May play a role in neural progenitor cells (NPCs) viability through the beta-catenin canonical signaling pathway by negatively regulating cell cycle arrest leading to inhibition of neuron apoptotic process (PubMed:27509850). During hippocampal development, regulates neuroblast proliferation and apoptotic cell death. Controls bone formation through non canonical Wnt signaling mediated via ISG15. Positively regulates bone regeneration through non canonical Wnt signaling (By similarity).By similarity1 Publication

GO - Molecular functioni

  • G-protein coupled receptor activity Source: GO_Central
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • Wnt-activated receptor activity Source: UniProtKB
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
SignaLinkiO00144.
SIGNORiO00144.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4047. FZD9.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein Sequence analysis

  • Note: Relocalizes DVL1 to the cell membrane leading to phosphorylation of DVL1 and AXIN1 relocalization to the cell membrane.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 229ExtracellularSequence analysisAdd BLAST207
Transmembranei230 – 250Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini251 – 266CytoplasmicSequence analysisAdd BLAST16
Transmembranei267 – 287Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini288 – 315ExtracellularSequence analysisAdd BLAST28
Transmembranei316 – 336Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini337 – 355CytoplasmicSequence analysisAdd BLAST19
Transmembranei356 – 376Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini377 – 400ExtracellularSequence analysisAdd BLAST24
Transmembranei401 – 421Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini422 – 447CytoplasmicSequence analysisAdd BLAST26
Transmembranei448 – 468Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini469 – 508ExtracellularSequence analysisAdd BLAST40
Transmembranei509 – 529Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini530 – 591CytoplasmicSequence analysisAdd BLAST62

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • endoplasmic reticulum membrane Source: UniProtKB
  • filopodium membrane Source: Ensembl
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: ProtInc
  • mitochondrial membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8326.
OpenTargetsiENSG00000188763.
PharmGKBiPA28464.

Polymorphism and mutation databases

BioMutaiFZD9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001300323 – 591Frizzled-9Add BLAST569

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 100PROSITE-ProRule annotation
Disulfide bondi47 ↔ 93PROSITE-ProRule annotation
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi84 ↔ 122PROSITE-ProRule annotation
Disulfide bondi111 ↔ 152PROSITE-ProRule annotation
Disulfide bondi115 ↔ 139PROSITE-ProRule annotation
Glycosylationi158N-linked (GlcNAc...)Sequence analysis1

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.
PeptideAtlasiO00144.
PRIDEiO00144.

PTM databases

iPTMnetiO00144.
PhosphoSitePlusiO00144.

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. Expressed in neural progenitor cells (PubMed:27509850).1 Publication

Gene expression databases

BgeeiENSG00000188763.
CleanExiHS_FZD3.
HS_FZD9.
GenevisibleiO00144. HS.

Interactioni

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliO00144.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 155FZPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 172Required for Wnt-activated receptor activityBy similarityAdd BLAST115
Regioni554 – 591Required for CTNNB1 accumulation and TCF transcription factor activityBy similarityAdd BLAST38

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi532 – 537Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain 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

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiO00144.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG091G0N5M.
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.
SM01330. Frizzled. 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.4. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO00144.
PhosphoSitePlusiO00144.

Polymorphism and mutation databases

BioMutaiFZD9.

Proteomic databases

PaxDbiO00144.
PeptideAtlasiO00144.
PRIDEiO00144.

Protocols and materials databases

DNASUi8326.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344575; ENSP00000345785; ENSG00000188763.
GeneIDi8326.
KEGGihsa:8326.
UCSCiuc003tyb.4. human.

Organism-specific databases

CTDi8326.
DisGeNETi8326.
GeneCardsiFZD9.
HGNCiHGNC:4047. FZD9.
MIMi601766. gene.
neXtProtiNX_O00144.
OpenTargetsiENSG00000188763.
PharmGKBiPA28464.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiO00144.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG091G0N5M.
PhylomeDBiO00144.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
SignaLinkiO00144.
SIGNORiO00144.

Miscellaneous databases

GeneWikiiFZD9.
GenomeRNAii8326.
PROiO00144.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188763.
CleanExiHS_FZD3.
HS_FZD9.
GenevisibleiO00144. HS.

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.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 146 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

Miscellaneous

Authors show that FZD9 is responsible for the cellular phenotype found in neural progenitor cells (NPCs) derived from Williams syndrome patients namely increased apoptosis of neural progenitor cells (NPCs).1 Publication

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

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 one 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.