fzd8

Functionⁱ

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 Wnt8, Wnt5A or Wnt3A induces expression of beta-catenin target genes. Displays an axis-inducing activity.1 Publication

GO - Molecular functionⁱ

G-protein coupled receptor activity Source: UniProtKB-KW

Complete GO annotation...

GO - Biological processⁱ

canonical Wnt signaling pathway
Source: BHF-UCL
Inferred from direct assayⁱ
- 18945944
multicellular organism development Source: UniProtKB-KW
positive regulation of sequence-specific DNA binding transcription factor activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 18945944

Complete GO annotation...

Keywordsⁱ

Molecular function	Developmental protein, G-protein coupled receptor, Receptor, Transducer
Biological process	Wnt signaling pathway

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Frizzled-8 Short name: Fz-8 Short name: Xfz8
Gene namesⁱ	Name:fzd8 Synonyms:fz8
Organismⁱ	Xenopus laevis (African clawed frog)
Taxonomic identifierⁱ	8355 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amphibia › Batrachia › Anura › Pipoidea › Pipidae › Xenopodinae › Xenopus › Xenopus

Organism-specific databases

Xenbaseⁱ	XB-GENE-865411. fzd8.

Xenbaseⁱ

XB-GENE-865411. fzd8.

Subcellular locationⁱ

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	24 – 239	ExtracellularSequence analysisAdd BLAST	216
Transmembraneⁱ	240 – 260	Helical; Name=1Sequence analysisAdd BLAST	21
Topological domainⁱ	261 – 271	CytoplasmicSequence analysisAdd BLAST	11
Transmembraneⁱ	272 – 292	Helical; Name=2Sequence analysisAdd BLAST	21
Topological domainⁱ	293 – 320	ExtracellularSequence analysisAdd BLAST	28
Transmembraneⁱ	321 – 341	Helical; Name=3Sequence analysisAdd BLAST	21
Topological domainⁱ	342 – 377	CytoplasmicSequence analysisAdd BLAST	36
Transmembraneⁱ	378 – 398	Helical; Name=4Sequence analysisAdd BLAST	21
Topological domainⁱ	399 – 407	ExtracellularSequence analysis	9
Transmembraneⁱ	408 – 428	Helical; Name=5Sequence analysisAdd BLAST	21
Topological domainⁱ	429 – 454	CytoplasmicSequence analysisAdd BLAST	26
Transmembraneⁱ	455 – 475	Helical; Name=6Sequence analysisAdd BLAST	21
Topological domainⁱ	476 – 505	ExtracellularSequence analysisAdd BLAST	30
Transmembraneⁱ	506 – 526	Helical; Name=7Sequence analysisAdd BLAST	21
Topological domainⁱ	527 – 581	CytoplasmicSequence analysisAdd BLAST	55

GO - Cellular componentⁱ

integral component of membrane Source: UniProtKB-KW
plasma membrane Source: UniProtKB-SubCell

Complete GO annotation...

Keywords - Cellular componentⁱ

Cell membrane, Membrane

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 23	Sequence analysisAdd BLAST		23
ChainⁱPRO_0000013002	24 – 581	Frizzled-8Add BLAST		558

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	28 ↔ 89	PROSITE-ProRule annotation
Disulfide bondⁱ	36 ↔ 82	PROSITE-ProRule annotation
Glycosylationⁱ	42	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	73 ↔ 111	PROSITE-ProRule annotation
Disulfide bondⁱ	100 ↔ 141	PROSITE-ProRule annotation
Disulfide bondⁱ	104 ↔ 128	PROSITE-ProRule annotation
Glycosylationⁱ	146	N-linked (GlcNAc...) asparagineSequence analysis	1

Keywords - PTMⁱ

Disulfide bond, Glycoprotein

Expressionⁱ

Developmental stageⁱ

First expressed at high levels in the late blastula stages. At early gastrula, expressed in the deep cells of the Spemann organizer prior to involution of the dorsal blastopore lip. Detected in presumptive neurectoderm as gastrulation proceeds. Becomes restricted to the anterior ectoderm by the end of gastrulation. At neurula stages, localized in the most anterior region of the embryo, mainly in the anterior ectoderm including telencephalic and cement gland regions.

Interactionⁱ

Subunit structureⁱ

Interacts with lypd6 and the interaction is strongly enhanced by wnt3a (PubMed:23987510).1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
FRIED	Q6EHH9	2	EBI-7735236,EBI-7735259

With

Entry

#Exp.

IntAct

Notes

FRIED

Q6EHH9

2

EBI-7735236,EBI-7735259

Protein-protein interaction databases

IntActⁱ	O93274. 1 interactor.
Molecular INTeraction database More...MINTⁱ	MINT-1893946.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O93274.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	24 – 144	FZPROSITE-ProRule annotationAdd BLAST		121

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	64 – 71	Palmitate-binding grooveBy similarity	8
Regionⁱ	88 – 93	Wnt-bindingBy similarity	6
Regionⁱ	140 – 146	Wnt-bindingBy similarity	7

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	529 – 534	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity		6
Motifⁱ	579 – 581	PDZ-binding		3

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

Belongs to the G-protein coupled receptor Fz/Smo family.Curated

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENⁱ	HBG006977.
KEGG Orthology (KO) More...KOⁱ	K02375.

Family and domain databases

InterProⁱ	View protein in InterPro IPR015526. Frizzled/SFRP. IPR000539. Frizzled/Smoothened_TM. IPR020067. Frizzled_dom. IPR017981. GPCR_2-like.
PANTHERⁱ	PTHR11309. PTHR11309. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit.
PRINTSⁱ	PR00489. FRIZZLED.
SMARTⁱ	View protein in SMART SM00063. FRI. 1 hit. SM01330. Frizzled. 1 hit.
SUPFAMⁱ	SSF63501. SSF63501. 1 hit.
PROSITEⁱ	View protein in PROSITE PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.

Sequenceⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

O93274-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MESLSLSLLL LVSWLQGSQC AAAKELSCQE ITVPLCKDIG YNYTYMPNQF 
        60         70         80         90        100
NHDTQDEAGM EVHQFWPLVV IHCSPDLKFF LCSMYTPICL EDYKKPLPPC 
       110        120        130        140        150
RSVCERARAG CAPLMRQYGF AWPDRMRCDR LPEQGNPDTL CMDYYNRTEQ 
       160        170        180        190        200
TTAAPSHPEP PKPPARSVPK GRTRVEPPRS RSRATGCESG CQCRAPMVQV 
       210        220        230        240        250
SNERHPLYNR VRTGQIPNCA MPCHNPFFSP EERTFTEFWI GLWSVLCFAS 
       260        270        280        290        300
TFATVSTFLI DMERFKYPER PIIFLSACYL LVSTGYLIRL IAGHEKVACS 
       310        320        330        340        350
RGELDLEHII HYETTGPALC TLVFLLIYFF GMASSIWWVI LSLTWFLAAG 
       360        370        380        390        400
MKWGNEAIAG YSQYFHLAAW LVPSIKSIAV LALSSVDGDP VAGICFVGNQ 
       410        420        430        440        450
NLDNLRGFVL APLVIYLFIG SMFLLAGFVS LFRIRSVIKQ GGTKTDKLEK 
       460        470        480        490        500
LMIRIGIFSV LYTVPATIVV ACFFYEQHNR QGWEVAHNCN SCQPEMAQPH 
       510        520        530        540        550
RPDYAVFMLK YFMCLVVGIT SGVWIWSGKT LESWRAFCTR CCWGSKATGG 
       560        570        580 
SMYSDVSTGL TWRSGTGSSV SCPKQMPLSQ V

Length:581

Mass (Da):65,379

Last modified:November 1, 1998 - v1

Checksum:ⁱ80890C408AB21E23

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	1 – 3	MES → MECPY (PubMed:9636083).Curated	3
Sequence conflictⁱ	7	S → L in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	10	L → V in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	14	W → G in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	20	C → S in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	135	G → S in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	171	G → S in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	175	V → A in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	185	T → P in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	216	I → T in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	237	E → D in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	494 – 496	PEM → SEG in AAC77361 (PubMed:9636083).Curated	3
Sequence conflictⁱ	500	H → R in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	547	A → T in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	565	G → A in AAC77361 (PubMed:9636083).Curated	1
Sequence conflictⁱ	572	C → Y in AAC77361 (PubMed:9636083).Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF017177 mRNA. Translation: AAC31121.1. AF033110 mRNA. Translation: AAC77361.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_001079144.1. NM_001085675.1. NP_001084206.1. NM_001090737.1.
UniGeneⁱ	Xl.293. Xl.412.

Genome annotation databases

GeneIDⁱ	373690. 399367.
KEGGⁱ	xla:373690. xla:399367.

Similar proteinsⁱ

Entry	Cluster members	Organisms	Length	Cluster ID	Cluster name	Size
O93274	UPI000854A739 B7ZQV9 UPI00084D17C2 A0A1L8FVD0 F6VM33	Xenopus laevis (African clawed frog) Nanorana parkeri Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	581	UniRef90_O93274	Cluster: Frizzled-8	6

Entry	Cluster members	Organisms	Length	Cluster ID	Cluster name	Size
O93274	UPI000854A739 B7ZQV9 UPI00084D17C2 A0A1L8FVD0 F6VM33 UPI00083C1A86 UPI0008FA46EC UPI0008FABFFE UPI0009A418EE UPI0009A40476 +8	Xenopus laevis (African clawed frog) Nanorana parkeri Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) Nicrophorus vespilloides Cyprinus carpio (Common carp) Rhincodon typus (whale shark) Anoplophora glabripennis (Asian longhorn beetle) (Anoplophora nobilis) Aethina tumida (Small hive beetle) Bemisia tabaci (Sweetpotato whitefly) (Aleurodes tabaci) Halyomorpha halys (Brown marmorated stink bug) (Pentatoma halys) And more	581	UniRef50_O93274	Cluster: Frizzled-8	19

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF017177 mRNA. Translation: AAC31121.1. AF033110 mRNA. Translation: AAC77361.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_001079144.1. NM_001085675.1. NP_001084206.1. NM_001090737.1.
UniGeneⁱ	Xl.293. Xl.412.

3D structure databases

ProteinModelPortalⁱ	O93274.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

IntActⁱ	O93274. 1 interactor.
Molecular INTeraction database More...MINTⁱ	MINT-1893946.

Protein family/group databases

GPCRDBⁱ	Search...

GPCRDBⁱ

Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	373690. 399367.
KEGGⁱ	xla:373690. xla:399367.

Organism-specific databases

CTDⁱ	373690. 399367.
Xenbaseⁱ	XB-GENE-865411. fzd8.

Phylogenomic databases

HOVERGENⁱ	HBG006977.
KEGG Orthology (KO) More...KOⁱ	K02375.

Family and domain databases

InterProⁱ	View protein in InterPro IPR015526. Frizzled/SFRP. IPR000539. Frizzled/Smoothened_TM. IPR020067. Frizzled_dom. IPR017981. GPCR_2-like.
PANTHERⁱ	PTHR11309. PTHR11309. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit.
PRINTSⁱ	PR00489. FRIZZLED.
SMARTⁱ	View protein in SMART SM00063. FRI. 1 hit. SM01330. Frizzled. 1 hit.
SUPFAMⁱ	SSF63501. SSF63501. 1 hit.
PROSITEⁱ	View protein in PROSITE PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	FZD8_XENLA
Accessionⁱ	O93274Primary (citable) accession number: O93274 Secondary accession number(s): Q9YI55
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
	Last sequence update:	November 1, 1998
	Last modified:	August 30, 2017
	This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Documents

7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries
SIMILARITY comments
Index of protein domains and families

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O93274 (FZD8_XENLA)

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Frizzled-8

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequenceⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ