Q9H461 (FZD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-8
Short name=Fz-8
Short name=hFz8

Gene names

Name:

FZD8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	694 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway 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. Coreceptor along with RYK of Wnt proteins, such as WNT1. Ref.3
Subunit structure	Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1. Interacts with GPOC, RSPO1 and RSPO3 By similarity. Ref.3 Ref.4
Subcellular location	Membrane; Multi-pass membrane protein. Golgi apparatus By similarity. Cell membrane; Multi-pass membrane protein By similarity. Note: Colocalizes with GOPC at the Golgi apparatus By similarity.
Tissue specificity	Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.
Domain	The PDZ-binding motif mediates interaction with GOPC By similarity. 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. Ref.5
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 Golgi apparatus 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	T cell differentiation in thymus Inferred from Biological aspect of Ancestor. Source: RefGenome axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor 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 negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell cell projection Inferred from Biological aspect of Ancestor. Source: RefGenome cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Traceable author statement Ref.1. Source: UniProtKB plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW Wnt-activated receptor activity Traceable author statement Ref.1. Source: UniProtKB Wnt-protein binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C1qa	P98086	3	EBI-6254212,EBI-299840	From a different organism.
WNT3A	P56704	2	EBI-6254212,EBI-6173037

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 694	667	Frizzled-8		PRO_0000013000
Regions
	Topological domain	28 – 275	248	Extracellular Potential
	Transmembrane	276 – 296	21	Helical; Name=1; Potential
	Topological domain	297 – 312	16	Cytoplasmic Potential
	Transmembrane	313 – 333	21	Helical; Name=2; Potential
	Topological domain	334 – 396	63	Extracellular Potential
	Transmembrane	397 – 417	21	Helical; Name=3; Potential
	Topological domain	418 – 439	22	Cytoplasmic Potential
	Transmembrane	440 – 460	21	Helical; Name=4; Potential
	Topological domain	461 – 483	23	Extracellular Potential
	Transmembrane	484 – 504	21	Helical; Name=5; Potential
	Topological domain	505 – 532	28	Cytoplasmic Potential
	Transmembrane	533 – 553	21	Helical; Name=6; Potential
	Topological domain	554 – 584	31	Extracellular Potential
	Transmembrane	585 – 605	21	Helical; Name=7; Potential
	Topological domain	606 – 694	89	Cytoplasmic Potential
	Domain	30 – 151	122	FZ
	Region	71 – 78	8	Palmitate-binding groove By similarity
	Region	95 – 100	6	Wnt-binding By similarity
	Region	147 – 152	6	Wnt-binding By similarity
	Motif	608 – 613	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	692 – 694	3	PDZ-binding
	Compositional bias	168 – 172	5	Poly-Pro
	Compositional bias	194 – 202	9	Poly-Gly
	Compositional bias	211 – 216	6	Poly-Gly
	Compositional bias	639 – 663	25	Poly-Gly
Amino acid modifications
	Glycosylation	49	1	N-linked (GlcNAc...) Potential
	Glycosylation	152	1	N-linked (GlcNAc...) Potential
	Glycosylation	475	1	N-linked (GlcNAc...) Potential
	Disulfide bond	35 ↔ 96		By similarity
	Disulfide bond	43 ↔ 89		By similarity
	Disulfide bond	80 ↔ 118		By similarity
	Disulfide bond	107 ↔ 148		By similarity
	Disulfide bond	111 ↔ 135		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9H461 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: E740CBFDA2A233EF	FASTA	694	73,300
	10 20 30 40 50 60 MEWGYLLEVT SLLAALALLQ RSSGAAAASA KELACQEITV PLCKGIGYNY TYMPNQFNHD 70 80 90 100 110 120 TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY KKPLPPCRSV CERAKAGCAP 130 140 150 160 170 180 LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD YNRTDLTTAA PSPPRRLPPP PPGEQPPSGS 190 200 210 220 230 240 GHGRPPGARP PHRGGGRGGG GGDAAAPPAR GGGGGGKARP PGGGAAPCEP GCQCRAPMVS 250 260 270 280 290 300 VSSERHPLYN RVKTGQIANC ALPCHNPFFS QDERAFTVFW IGLWSVLCFV STFATVSTFL 310 320 330 340 350 360 IDMERFKYPE RPIIFLSACY LFVSVGYLVR LVAGHEKVAC SGGAPGAGGA GGAGGAAAGA 370 380 390 400 410 420 GAAGAGAGGP GGRGEYEELG AVEQHVRYET TGPALCTVVF LLVYFFGMAS SIWWVILSLT 430 440 450 460 470 480 WFLAAGMKWG NEAIAGYSQY FHLAAWLVPS VKSIAVLALS SVDGDPVAGI CYVGNQSLDN 490 500 510 520 530 540 LRGFVLAPLV IYLFIGTMFL LAGFVSLFRI RSVIKQQDGP TKTHKLEKLM IRLGLFTVLY 550 560 570 580 590 600 TVPAAVVVAC LFYEQHNRPR WEATHNCPCL RDLQPDQARR PDYAVFMLKY FMCLVVGITS 610 620 630 640 650 660 GVWVWSGKTL ESWRSLCTRC CWASKGAAVG GGAGATAAGG GGGPGGGGGG GPGGGGGPGG 670 680 690 GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2." Saitoh T., Hirai M., Katoh M. Int. J. Oncol. 18:991-996(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6." Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X. Curr. Biol. 11:951-961(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRP5 AND LRP6 IN THE WNT-FZD-LRP5-LRP6 COMPLEX, FUNCTION.
[4]	"Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin." Li X., Zhang J., Cao Z., Wu J., Shi Y. Protein Sci. 15:2149-2158(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GOPC.
[5]	"ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner." Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F. Nature 485:195-200(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY ZNRF3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB043703 mRNA. Translation: BAB41064.1. AL121749 Genomic DNA. Translation: CAC10185.1.
IPI	IPI00010807.
RefSeq	NP_114072.1. NM_031866.2.
UniGene	Hs.302634.
3D structure databases
ProteinModelPortal	Q9H461.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H461. 2 interactions.
STRING	9606.ENSP00000363826.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9H461.
Polymorphism databases
DMDM	17433053.
Proteomic databases
PaxDb	Q9H461.
PRIDE	Q9H461.
Protocols and materials databases
DNASU	8325.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374694; ENSP00000363826; ENSG00000177283.
GeneID	8325.
KEGG	hsa:8325.
UCSC	uc001iyz.1. human.
Organism-specific databases
CTD	8325.
GeneCards	GC10M035927.
HGNC	HGNC:4046. FZD8.
HPA	HPA045025.
MIM	606146. gene.
neXtProt	NX_Q9H461.
PharmGKB	PA28463.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257258.
HOGENOM	HOG000233236.
HOVERGEN	HBG006977.
InParanoid	Q9H461.
KO	K02375.
OMA	CHNPYFT.
OrthoDB	EOG4B5P5T.
PhylomeDB	Q9H461.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q9H461.
CleanEx	HS_FZD8.
Genevestigator	Q9H461.
GermOnline	ENSG00000177283. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026545. FZD8. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF28. PTHR11309:SF28. 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
GenomeRNAi	8325.
NextBio	31175.
SOURCE	Search...

Entry information

Entry name

FZD8_HUMAN

Accession

Primary (citable) accession number: Q9H461

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.