Q61089 (FZD6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-6
Short name=Fz-6
Short name=mFz6

Gene names

Name:

Fzd6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	709 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein Ref.3.
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.
Disruption phenotype	Half of the males without the gene, but not females, display abnormal claw morphology or absent claws compared to wild-type. At the age of 2 to 3 months, the claws disappear or become rudimentary on the hind limbs. Ref.4
Sequence similarities	Belongs to the G-protein coupled receptor Fz/Smo family. Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor signaling pathway, planar cell polarity pathway Inferred from direct assay PubMed 18606138. Source: MGI angiogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome cell proliferation in midbrain Inferred from genetic interaction PubMed 19842188. Source: MGI establishment of planar polarity Inferred from genetic interaction PubMed 16495441. Source: MGI gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome hair follicle development Inferred from mutant phenotype PubMed 15169958PubMed 17172440. Source: MGI inner ear morphogenesis Inferred from genetic interaction PubMed 16495441. Source: MGI negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara neural tube closure Inferred from genetic interaction PubMed 16495441. Source: MGI platelet activation Inferred from mutant phenotype PubMed 19901330. Source: MGI regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	apical part of cell Inferred from direct assay PubMed 16495441. Source: MGI apicolateral plasma membrane Inferred from direct assay PubMed 17376975. Source: MGI cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 709	691	Frizzled-6		PRO_0000012995
Regions
	Topological domain	19 – 201	183	Extracellular Potential
	Transmembrane	202 – 222	21	Helical; Name=1; Potential
	Topological domain	223 – 233	11	Cytoplasmic Potential
	Transmembrane	234 – 254	21	Helical; Name=2; Potential
	Topological domain	255 – 284	30	Extracellular Potential
	Transmembrane	285 – 305	21	Helical; Name=3; Potential
	Topological domain	306 – 324	19	Cytoplasmic Potential
	Transmembrane	325 – 345	21	Helical; Name=4; Potential
	Topological domain	346 – 370	25	Extracellular Potential
	Transmembrane	371 – 391	21	Helical; Name=5; Potential
	Topological domain	392 – 416	25	Cytoplasmic Potential
	Transmembrane	417 – 437	21	Helical; Name=6; Potential
	Topological domain	438 – 473	36	Extracellular Potential
	Transmembrane	474 – 494	21	Helical; Name=7; Potential
	Topological domain	495 – 709	215	Cytoplasmic Potential
	Domain	19 – 132	114	FZ
	Motif	498 – 503	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Amino acid modifications
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
	Disulfide bond	24 ↔ 85		By similarity
	Disulfide bond	32 ↔ 78		By similarity
	Disulfide bond	69 ↔ 106		By similarity
	Disulfide bond	95 ↔ 129		By similarity
	Disulfide bond	99 ↔ 123		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q61089 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 01374A9EC9122484	FASTA	709	79,082
	10 20 30 40 50 60 MERSPFLLAC ILLPLVRGHS LFTCEPITVP RCMKMTYNMT FFPNLMGHYD QGIAAVEMGH 70 80 90 100 110 120 FLHLANLECS PNIEMFLCQA FIPTCTEQIH VVLPCRKLCE KIVSDCKKLM DTFGIRWPEE 130 140 150 160 170 180 LECNRLPHCD DTVPVTSHPH TELSGPQKKS DQVPRDIGFW CPKHLRTSGD QGYRFLGIEQ 190 200 210 220 230 240 CAPPCPNMYF KSDELDFAKS FIGIVSIFCL CATLFTFLTF LIDVRRFRYP ERPIIYYSVC 250 260 270 280 290 300 YSIVSLMYFV GFLLGNSTAC NKADEKLELG DTVVLGSKNK ACSVVFMFLY FFTMAGTVWW 310 320 330 340 350 360 VILTITWFLA AGRKWSCEAI EQKAVWFHAV AWGAPGFLTV MLLAMNKVEG DNISGVCFVG 370 380 390 400 410 420 LYDLDASRYF VLLPLCLCVF VGLSLLLAGI ISLNHVRQVI QHDGRNQEKL KKFMIRIGVF 430 440 450 460 470 480 SGLYLVPLVT LLGCYVYELV NRITWEMTWF SDHCHQYRIP CPYQANPKAR PELALFMIKY 490 500 510 520 530 540 LMTLIVGISA VFWVGSKKTC TEWAGFFKRN RKRDPISESR RVLQESCEFF LKHNSKVKHK 550 560 570 580 590 600 KKHGAPGPHR LKVISKSMGT STGATTNHGT SAMAIADHDY LGQETSTEVH TSPEASVKEG 610 620 630 640 650 660 RADRANTPSA KDRDCGESAG PSSKLSGNRN GRESRAGGLK ERSNGSEGAP SEGRVSPKSS 670 680 690 700 VPETGLIDCS TSQAASSPEP TSLKGSTSLP VHSASRARKE QGAGSHSDA

References

[1]	"A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled." Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J. J. Biol. Chem. 271:4468-4476(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner." Sheldahl L.C., Park M., Malbon C.C., Moon R.T. Curr. Biol. 9:695-698(1999) [PubMed] [Europe PMC] [Abstract] Cited for: WNT-MEDIATED PKC ACTIVATION.
[3]	"Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein." Hsieh J.C., Rattner A., Smallwood P.M., Nathans J. Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[4]	"Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia." Frojmark A.S., Schuster J., Sobol M., Entesarian M., Kilander M.B., Gabrikova D., Nawaz S., Baig S.M., Schulte G., Klar J., Dahl N. Am. J. Hum. Genet. 88:852-860(2011) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43319 mRNA. Translation: AAC52431.1.
IPI	IPI00117095.
RefSeq	NP_001155966.1. NM_001162494.1. NP_032082.3. NM_008056.3.
UniGene	Mm.4769.
3D structure databases
ProteinModelPortal	Q61089.
SMR	Q61089. Positions 24-127.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61089. 1 interaction.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q61089.
Proteomic databases
PRIDE	Q61089.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022906; ENSMUSP00000022906; ENSMUSG00000022297. ENSMUST00000179165; ENSMUSP00000136328; ENSMUSG00000022297.
GeneID	14368.
KEGG	mmu:14368.
UCSC	uc007vny.2. mouse.
Organism-specific databases
CTD	8323.
MGI	MGI:108474. Fzd6.
Phylogenomic databases
eggNOG	NOG262811.
GeneTree	ENSGT00660000095356.
HOGENOM	HOG000233237.
HOVERGEN	HBG006977.
InParanoid	Q61089.
KO	K02376.
OMA	CPYQAKA.
OrthoDB	EOG4QC153.
Gene expression databases
ArrayExpress	Q61089.
Bgee	Q61089.
CleanEx	MM_FZD6.
Genevestigator	Q61089.
GermOnline	ENSMUSG00000022297. Mus musculus.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026543. FZD6. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF21. PTHR11309:SF21. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FZD6. mouse.
NextBio	285845.
SOURCE	Search...

Entry information

Entry name

FZD6_MOUSE

Accession

Primary (citable) accession number: Q61089

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program