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Protein

Frizzled-8

Gene

Fzd8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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 signalsomes. 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_323768. Class B/2 (Secretin family receptors).

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-8
Short name:
Fz-8
Gene namesi
Name:Fzd8
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1560525. Fzd8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 271244ExtracellularSequence AnalysisAdd
BLAST
Transmembranei272 – 29221Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini293 – 30816CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei309 – 32921Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini330 – 39364ExtracellularSequence AnalysisAdd
BLAST
Transmembranei394 – 41421Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini415 – 43622CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei437 – 45721Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini458 – 48023ExtracellularSequence AnalysisAdd
BLAST
Transmembranei481 – 50121Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini502 – 52928CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei530 – 55021Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini551 – 58131ExtracellularSequence AnalysisAdd
BLAST
Transmembranei582 – 60221Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini603 – 68482CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 684657Frizzled-8PRO_0000278650Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi472 – 4721N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ498S8.
PRIDEiQ498S8.

PTM databases

PhosphoSiteiQ498S8.

Expressioni

Gene expression databases

ExpressionAtlasiQ498S8. baseline.
GenevestigatoriQ498S8.

Interactioni

Subunit structurei

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 (via the PDZ-binding motif) with GPOC (via its PDZ domain). Interacts with RSPO1 and RSPO3 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ498S8.
SMRiQ498S8. Positions 32-153.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 151122FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni71 – 788Palmitate-binding grooveBy similarity
Regioni95 – 1006Wnt-bindingBy similarity
Regioni147 – 1526Wnt-bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi605 – 6106Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi682 – 6843PDZ-bindingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi161 – 22666Pro-richAdd
BLAST
Compositional biasi168 – 1736Poly-Pro
Compositional biasi639 – 65315Poly-GlyAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ498S8.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
PhylomeDBiQ498S8.
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.
[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.

Q498S8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY
60 70 80 90 100
TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY
110 120 130 140 150
KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD
160 170 180 190 200
YNRTDLTTAA PSPPRRLPPP QPGEQPPSGS GHSRPPGARP PHRGGSSRGS
210 220 230 240 250
GDTAAAPPSR GGKARPPGGG AAPCEPGCQC RAPMVSVSSE RHPLYNRVKT
260 270 280 290 300
GQIANCALPC HNPFFSQDER AFTVFWIGLW SVLCFVSTFA TVSTFLIDME
310 320 330 340 350
RFKYPERPII FLSACYLFVS VGYLVRLVAG HEKVACSGGA PGAGGAGGAG
360 370 380 390 400
GAATAGAGAA GAGASSPGAR GEYEELGAVE QHVRYETTGP ALCTVVFLLV
410 420 430 440 450
YFFGMASSIW WVILSLTWFL AAGMKWGNEA IAGYSQYFHL AAWLVPSVKS
460 470 480 490 500
IAVLALSSVD GDPVAGICYV GNQSLDNLRG FVLAPLVIYL FIGTMFLLAG
510 520 530 540 550
FVSLFRIRSV IKQQGGPTKT HKLEKLMIRL GLFTVLYTVP AAVVVACLFY
560 570 580 590 600
EQHNRPRWEA THNCPCLRDL QPDQARRPDY AVFMLKYFMC LVVGITSGVW
610 620 630 640 650
VWSGKTLESW RALCTRCCWA SKGAAVGAGA GGSGPGGGGP GPGGGGGHGG
660 670 680
GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV
Length:684
Mass (Da):73,009
Last modified:September 13, 2005 - v1
Checksum:iEEBA871326749B69
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC100088 mRNA. Translation: AAI00089.1.
RefSeqiNP_001037716.1. NM_001044251.2.
XP_003751769.1. XM_003751721.3.
XP_006254204.1. XM_006254142.2.
UniGeneiRn.234505.

Genome annotation databases

EnsembliENSRNOT00000058837; ENSRNOP00000055627; ENSRNOG00000038571.
ENSRNOT00000073575; ENSRNOP00000067651; ENSRNOG00000048236.
GeneIDi100909849.
364754.
KEGGirno:100909849.
rno:364754.
UCSCiRGD:1560525. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC100088 mRNA. Translation: AAI00089.1.
RefSeqiNP_001037716.1. NM_001044251.2.
XP_003751769.1. XM_003751721.3.
XP_006254204.1. XM_006254142.2.
UniGeneiRn.234505.

3D structure databases

ProteinModelPortaliQ498S8.
SMRiQ498S8. Positions 32-153.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

PTM databases

PhosphoSiteiQ498S8.

Proteomic databases

PaxDbiQ498S8.
PRIDEiQ498S8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000058837; ENSRNOP00000055627; ENSRNOG00000038571.
ENSRNOT00000073575; ENSRNOP00000067651; ENSRNOG00000048236.
GeneIDi100909849.
364754.
KEGGirno:100909849.
rno:364754.
UCSCiRGD:1560525. rat.

Organism-specific databases

CTDi8325.
RGDi1560525. Fzd8.

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ498S8.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
PhylomeDBiQ498S8.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_323768. Class B/2 (Secretin family receptors).

Miscellaneous databases

NextBioi685973.
PROiQ498S8.

Gene expression databases

ExpressionAtlasiQ498S8. baseline.
GenevestigatoriQ498S8.

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.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.

Entry informationi

Entry nameiFZD8_RAT
AccessioniPrimary (citable) accession number: Q498S8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: September 13, 2005
Last modified: April 1, 2015
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.