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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

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-8
Short name:
Fz-8
Gene namesi
Name:Fzd8
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1560525. Fzd8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 271ExtracellularSequence analysisAdd BLAST244
Transmembranei272 – 292Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini293 – 308CytoplasmicSequence analysisAdd BLAST16
Transmembranei309 – 329Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini330 – 393ExtracellularSequence analysisAdd BLAST64
Transmembranei394 – 414Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini415 – 436CytoplasmicSequence analysisAdd BLAST22
Transmembranei437 – 457Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini458 – 480ExtracellularSequence analysisAdd BLAST23
Transmembranei481 – 501Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini502 – 529CytoplasmicSequence analysisAdd BLAST28
Transmembranei530 – 550Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini551 – 581ExtracellularSequence analysisAdd BLAST31
Transmembranei582 – 602Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini603 – 684CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000027865028 – 684Frizzled-8Add BLAST657

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation
Glycosylationi49N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation
Glycosylationi152N-linked (GlcNAc...)Sequence analysis1
Glycosylationi472N-linked (GlcNAc...)Sequence analysis1

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

PhosphoSitePlusiQ498S8.

Expressioni

Gene expression databases

BgeeiENSRNOG00000038571.
GenevisibleiQ498S8. RN.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067651.

Structurei

3D structure databases

ProteinModelPortaliQ498S8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 151FZPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni71 – 78Palmitate-binding grooveBy similarity8
Regioni95 – 100Wnt-bindingBy similarity6
Regioni147 – 152Wnt-bindingBy similarity6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi605 – 610Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi682 – 684PDZ-bindingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi161 – 226Pro-richAdd BLAST66
Compositional biasi168 – 173Poly-Pro6
Compositional biasi639 – 653Poly-GlyAdd BLAST15

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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ498S8.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG091G0N5M.
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. 3 hits.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 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_003751721.4.
XP_006254204.1. XM_006254142.3.
UniGeneiRn.234505.

Genome annotation databases

EnsembliENSRNOT00000058837; ENSRNOP00000055627; ENSRNOG00000059244.
ENSRNOT00000073575; ENSRNOP00000067651; ENSRNOG00000061031.
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_003751721.4.
XP_006254204.1. XM_006254142.3.
UniGeneiRn.234505.

3D structure databases

ProteinModelPortaliQ498S8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067651.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ498S8.

Proteomic databases

PaxDbiQ498S8.
PRIDEiQ498S8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000058837; ENSRNOP00000055627; ENSRNOG00000059244.
ENSRNOT00000073575; ENSRNOP00000067651; ENSRNOG00000061031.
GeneIDi100909849.
364754.
KEGGirno:100909849.
rno:364754.
UCSCiRGD:1560525. rat.

Organism-specific databases

CTDi8325.
RGDi1560525. Fzd8.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ498S8.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ498S8.
TreeFamiTF317907.

Miscellaneous databases

PROiQ498S8.

Gene expression databases

BgeeiENSRNOG00000038571.
GenevisibleiQ498S8. RN.

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. 3 hits.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 90 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

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 one 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.