Reviewed, UniProtKB/Swiss-Prot Q9H461 (FZD8_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

FZD8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 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.
Subunit structure	Interacts with GOPC. Interacts with RSPO1 and RSPO3 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
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 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 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	Membrane
Domain	Signal Transmembrane
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Ref.1 Traceable author statement. Source: UniProtKB
Molecular function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW Wnt receptor activity Ref.1 Traceable author statement. Source: UniProtKB non-G-protein coupled 7TM receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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	1 Potential
	Topological domain	297 – 312	16	Cytoplasmic Potential
	Transmembrane	313 – 333	21	2 Potential
	Topological domain	334 – 396	63	Extracellular Potential
	Transmembrane	397 – 417	21	3 Potential
	Topological domain	418 – 439	22	Cytoplasmic Potential
	Transmembrane	440 – 460	21	4 Potential
	Topological domain	461 – 483	23	Extracellular Potential
	Transmembrane	484 – 504	21	5 Potential
	Topological domain	505 – 532	28	Cytoplasmic Potential
	Transmembrane	533 – 553	21	6 Potential
	Topological domain	554 – 584	31	Extracellular Potential
	Transmembrane	585 – 605	21	7 Potential
	Topological domain	606 – 694	89	Cytoplasmic Potential
	Domain	30 – 151	122	FZ
	Motif	608 – 613	6	Lys-Thr-X-X-X-Trp motif
	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)
	Q9H461-1 [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: 11295046] [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: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB043703 mRNA. Translation: BAB41064.1. AL121749 Genomic DNA. Translation: CAC10185.1.
IPI	IPI00010807.
RefSeq	NP_114072.1.
UniGene	Hs.302634
3D structure databases
HSSP	HSSP built from PDB template 1IJY based on UniProtKB Q61091.
SMR	Q9H461. Positions 32-153.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	Q9H461.
Genome annotation databases
Ensembl	ENSG00000177283. Homo sapiens. [Contig view]
GeneID	8325.
KEGG	hsa:8325.
Organism-specific databases
GeneCards	GC10M035967.
H-InvDB	HIX0035305.
HGNC	HGNC:4046. FZD8.
MIM	606146. gene.
PharmGKB	PA28463.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9H461.
HOVERGEN	Q9H461.
OMA	Q9H461. GHEKVAC.
Gene expression databases
ArrayExpress	Q9H461.
Bgee	Q9H461.
CleanEx	HS_FZD8.
GermOnline	ENSG00000177283. Homo sapiens.
Family and domain databases
InterPro	IPR000539. Frizzled. IPR000024. Frizzled_Cys-rich. IPR015526. Frizzled_related. IPR017981. GPCR_2-like. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	June 16, 2009
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)