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Protein

Frizzled-9

Gene

Fzd9

Organism
Mus musculus (Mouse)
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 (PubMed:24860427). 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 (By similarity). During hippocampal development, regulates neuroblast proliferation and apoptotic cell death (PubMed:15930120). Controls bone formation through non canonical Wnt signaling mediated via ISG15 (PubMed:21402791). Positively regulates bone regeneration through non canonical Wnt signaling (PubMed:24391920).By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

  • B cell differentiation Source: MGI
  • bone regeneration Source: UniProtKB
  • canonical Wnt signaling pathway Source: GO_Central
  • learning or memory Source: MGI
  • negative regulation of cell cycle arrest Source: UniProtKB
  • negative regulation of mitochondrial depolarization Source: UniProtKB
  • negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
  • negative regulation of necroptotic process Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of skeletal muscle acetylcholine-gated channel clustering Source: UniProtKB
  • neuroblast proliferation Source: MGI
  • non-canonical Wnt signaling pathway Source: GO_Central
  • ossification Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of bone mineralization Source: UniProtKB
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of neural precursor cell proliferation Source: UniProtKB
  • regulation of cytosolic calcium ion concentration Source: UniProtKB
  • regulation of skeletal muscle acetylcholine-gated channel clustering Source: UniProtKB
  • release of cytochrome c from mitochondria Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-9
Short name:
Fz-9
Short name:
mFz3
Short name:
mFz9
Alternative name(s):
CD_antigen: CD349
Gene namesi
Name:Fzd9
Synonyms:Fzd3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1313278. Fzd9.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 230ExtracellularAdd BLAST207
Transmembranei231 – 251Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini252 – 267CytoplasmicSequence analysisAdd BLAST16
Transmembranei268 – 288Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini289 – 316ExtracellularSequence analysisAdd BLAST28
Transmembranei317 – 337Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini338 – 356CytoplasmicSequence analysisAdd BLAST19
Transmembranei357 – 377Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini378 – 401ExtracellularSequence analysisAdd BLAST24
Transmembranei402 – 422Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini423 – 448CytoplasmicSequence analysisAdd BLAST26
Transmembranei449 – 469Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini470 – 509ExtracellularSequence analysisAdd BLAST40
Transmembranei510 – 530Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini531 – 592CytoplasmicSequence analysisAdd BLAST62

GO - Cellular componenti

  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB
  • filopodium membrane Source: MGI
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: GO_Central
  • mitochondrial membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Homozygous Fzd9 knockout mice show deficits in spatial memory behaviors. Heterozygous and homozygous Fzd9 knockout mice appear healthy, develop normally, and are fertile (PubMed:15930120). Homozygous Fzd9 knockout mice display osteopenia (PubMed:21402791).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001300424 – 592Frizzled-9Add BLAST569

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi40 ↔ 101PROSITE-ProRule annotation
Disulfide bondi48 ↔ 94PROSITE-ProRule annotation
Glycosylationi54N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi85 ↔ 123PROSITE-ProRule annotation
Disulfide bondi112 ↔ 153PROSITE-ProRule annotation
Disulfide bondi116 ↔ 140PROSITE-ProRule annotation
Glycosylationi159N-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

PaxDbiQ9R216.
PRIDEiQ9R216.

PTM databases

iPTMnetiQ9R216.
PhosphoSitePlusiQ9R216.

Expressioni

Tissue specificityi

In the embryo, found in the neural tube, trunk skeletal muscle precursors (myotomes), limb skeletal anlagen, craniofacial regions and nephric ducts. In the adult, expression is abundant in heart, brain, testis and skeletal muscle. In the testis, expressed in all spermatogenic cell types. Lower levels in adult lung, liver and kidney. Barely detectable in spleen. Expressed also in chondrocytes.

Developmental stagei

Not detected at embryonic day 7 (E7), weakly at E11 and strongly at E15 and E17. Expression covers the entire neural tube at 9.5 dpc, decreases at 10.5 dpc and becomes detectable only in the lumbar to tail regions at 11.5 dpc. In the somites, expression begins at 10.5 dpc to become up-regulated all along the rostrocaudal trunk axis at 11.5 dpc. In craniofacial territories, expression is first detected at 11.5 dpc in restricted areas of the nose, the maxillar mandibular and second branchial arch anlagen. At 11.5 dpc, predominantly expressed in restricted areas of the nose, dorsally to the eye and in the caudal pharyngeal region. Highly expressed at early stages of neuromuscular junction assembly (E14.5) and gradually decreases as development proceeds, being more than about 4-fold less expressed in E19.5.1 Publication

Inductioni

Increases during the initial stages of osteoblast differentiation.1 Publication

Gene expression databases

BgeeiENSMUSG00000049551.
CleanExiMM_FZD3.
MM_FZD9.
GenevisibleiQ9R216. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9R216. 2 interactors.
STRINGi10090.ENSMUSP00000053551.

Structurei

3D structure databases

ProteinModelPortaliQ9R216.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 156FZPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni59 – 173Required for Wnt-activated receptor activityBy similarityAdd BLAST115
Regioni555 – 592Required for CTNNB1 accumulation and TCF transcription factor activityBy similarityAdd BLAST38

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi533 – 538Lys-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.
InParanoidiQ9R216.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ9R216.
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.

Q9R216-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVPPLLRGA LLLWQLLATG GAALEIGRFD PERGRGPAPC QAMEIPMCRG
60 70 80 90 100
IGYNLTRMPN LLGHTSQGEA AAQLAEFSPL VQYGCHSHLR FFLCSLYAPM
110 120 130 140 150
CTDQVSTPIP ACRPMCEQAR LRCAPIMEQF NFGWPDSLDC ARLPTRNDPH
160 170 180 190 200
ALCMEAPENA TAGPTEPHKG LGMLPVAPRP ARPPGDSAPG PGSGGTCDNP
210 220 230 240 250
EKFQYVEKSR SCAPRCGPGV EVFWSRRDKD FALVWMAVWS ALCFFSTAFT
260 270 280 290 300
VFTFLLEPHR FQYPERPIIF LSMCYNVYSL AFLIRAVAGA QSVACDQEAG
310 320 330 340 350
ALYVIQEGLE NTGCTLVFLL LYYFGMASSL WWVVLTLTWF LAAGKKWGHE
360 370 380 390 400
AIEAHGSYFH MAAWGLPALK TIVVLTLRKV AGDELTGLCY VASMDPAALT
410 420 430 440 450
GFVLVPLSCY LVLGTSFLLT GFVALFHIRK IMKTGGTNTE KLEKLMVKIG
460 470 480 490 500
VFSILYTVPA TCVIVCYVYE RLNMDFWRLR ATEQPCTAAT VPGGRRDCSL
510 520 530 540 550
PGGSVPTVAV FMLKIFMSLV VGITSGVWVW SSKTFQTWQS LCYRKMAAGR
560 570 580 590
ARAKACRTPG GYGRGTHCHY KAPTVVLHMT KTDPSLENPT HL
Length:592
Mass (Da):64,995
Last modified:May 1, 2000 - v1
Checksum:i21B2D4F8CE232965
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66S → P in AAB87503 (Ref. 3) Curated1
Sequence conflicti73 – 74QL → HC in BAB32311 (PubMed:16141072).Curated2
Sequence conflicti93L → F in BAB32311 (PubMed:16141072).Curated1
Sequence conflicti144P → S in CAB44237 (Ref. 4) Curated1
Sequence conflicti221E → K in CAB44237 (Ref. 4) Curated1
Sequence conflicti237A → P in CAB44237 (Ref. 4) Curated1
Sequence conflicti308G → D in AAB87503 (Ref. 3) Curated1
Sequence conflicti374V → F in CAB44237 (Ref. 4) Curated1
Sequence conflicti592L → P in BAB32311 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF088850 Genomic DNA. Translation: AAD27789.1.
AK021164 mRNA. Translation: BAB32311.1.
AF033585 mRNA. Translation: AAB87503.2.
Y17709 mRNA. Translation: CAB44237.1.
CCDSiCCDS51661.1.
RefSeqiNP_034376.1. NM_010246.1.
UniGeneiMm.6256.

Genome annotation databases

EnsembliENSMUST00000062572; ENSMUSP00000053551; ENSMUSG00000049551.
GeneIDi14371.
KEGGimmu:14371.
UCSCiuc008zya.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF088850 Genomic DNA. Translation: AAD27789.1.
AK021164 mRNA. Translation: BAB32311.1.
AF033585 mRNA. Translation: AAB87503.2.
Y17709 mRNA. Translation: CAB44237.1.
CCDSiCCDS51661.1.
RefSeqiNP_034376.1. NM_010246.1.
UniGeneiMm.6256.

3D structure databases

ProteinModelPortaliQ9R216.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9R216. 2 interactors.
STRINGi10090.ENSMUSP00000053551.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9R216.
PhosphoSitePlusiQ9R216.

Proteomic databases

PaxDbiQ9R216.
PRIDEiQ9R216.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000062572; ENSMUSP00000053551; ENSMUSG00000049551.
GeneIDi14371.
KEGGimmu:14371.
UCSCiuc008zya.2. mouse.

Organism-specific databases

CTDi8326.
MGIiMGI:1313278. Fzd9.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9R216.
KOiK02842.
OMAiNALCMEA.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ9R216.
TreeFamiTF317907.

Miscellaneous databases

PROiQ9R216.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000049551.
CleanExiMM_FZD3.
MM_FZD9.
GenevisibleiQ9R216. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q9R216
Secondary accession number(s): O35494, Q9CX16, Q9R2B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 1, 2000
Last modified: November 30, 2016
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

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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.