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Protein

Frizzled-5

Gene

Fzd5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins (PubMed:11092808, PubMed:18230341). Can activate WNT2, WNT10B, WNT5A, but not WNT2B or WNT4 (in vitro); the in vivo situation may be different since not all of these are known to be coexpressed (PubMed:11092808). In neurons, activation of WNT7A promotes formation of synapses (By similarity). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:18230341). The canonical Wnt/beta-catenin 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 (PubMed:18230341). 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 (Probable). Plays a role in yolk sac angiogenesis and in placental vascularization (PubMed:11092808).By similarityCurated2 Publications

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: MGI
  • anterior/posterior axis specification, embryo Source: MGI
  • apoptotic process involved in morphogenesis Source: MGI
  • branching involved in labyrinthine layer morphogenesis Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • cell maturation Source: MGI
  • cellular response to molecule of bacterial origin Source: MGI
  • chorionic trophoblast cell differentiation Source: MGI
  • embryonic axis specification Source: MGI
  • embryonic camera-type eye development Source: MGI
  • embryonic camera-type eye morphogenesis Source: CACAO
  • labyrinthine layer blood vessel development Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • non-canonical Wnt signaling pathway Source: GO_Central
  • positive regulation of interferon-gamma production Source: MGI
  • positive regulation of interleukin-1 beta secretion Source: ARUK-UCL
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of protein targeting to mitochondrion Source: MGI
  • positive regulation of T cell cytokine production Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • positive regulation of tumor necrosis factor secretion Source: ARUK-UCL
  • post-embryonic camera-type eye development Source: CACAO
  • regulation of autophagy of mitochondrion Source: MGI
  • regulation of bicellular tight junction assembly Source: MGI
  • regulation of canonical Wnt signaling pathway Source: MGI
  • regulation of chorionic trophoblast cell proliferation Source: MGI
  • Spemann organizer formation Source: MGI
  • syncytiotrophoblast cell differentiation involved in labyrinthine layer development Source: MGI
  • T cell differentiation in thymus Source: MGI
  • vasculature development Source: MGI
  • Wnt signaling pathway Source: MGI
  • Wnt signaling pathway involved in dorsal/ventral axis specification Source: MGI

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processAngiogenesis, Differentiation, Wnt signaling pathway
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-4086398 Ca2+ pathway
R-MMU-4608870 Asymmetric localization of PCP proteins
R-MMU-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-MMU-4641263 Regulation of FZD by ubiquitination
R-MMU-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-5
Short name:
Fz-5
Short name:
mFz5
Gene namesi
Name:Fzd5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:108571 Fzd5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 238ExtracellularSequence analysisAdd BLAST212
Transmembranei239 – 259Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini260 – 270CytoplasmicSequence analysisAdd BLAST11
Transmembranei271 – 291Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini292 – 315ExtracellularSequence analysisAdd BLAST24
Transmembranei316 – 336Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini337 – 358CytoplasmicSequence analysisAdd BLAST22
Transmembranei359 – 379Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini380 – 402ExtracellularSequence analysisAdd BLAST23
Transmembranei403 – 423Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini424 – 449CytoplasmicSequence analysisAdd BLAST26
Transmembranei450 – 470Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini471 – 500ExtracellularSequence analysisAdd BLAST30
Transmembranei501 – 521Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini522 – 585CytoplasmicSequence analysisAdd BLAST64

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Golgi apparatus, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Full embryonic lethality around 12.5 dpc, due to defects in yolk sac and placenta vascularization.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000024393627 – 585Frizzled-5Add BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 94PROSITE-ProRule annotation
Disulfide bondi41 ↔ 87PROSITE-ProRule annotation
Glycosylationi47N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi78 ↔ 116PROSITE-ProRule annotation
Disulfide bondi105 ↔ 147PROSITE-ProRule annotation
Disulfide bondi109 ↔ 133PROSITE-ProRule annotation
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Ubiquitinated by RNF43 and ZNRF3, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9EQD0
PRIDEiQ9EQD0

PTM databases

iPTMnetiQ9EQD0
PhosphoSitePlusiQ9EQD0

Expressioni

Tissue specificityi

Detected in hippocampus (at protein level) (PubMed:20530549). Expressed in eye, kidney, lung, chondrocytes, epithelial cells of the small intestine and gobelet cells of the colon (PubMed:8626800).2 Publications

Developmental stagei

Detected at low levels in neonate brain; expression levels increase steadily during the first four weeks after birth and show a further increase in adults (at protein level) (PubMed:20530549). Expressed in the yolk sac, placenta, eye and lung bud at 9.5 dpc. At 10.5 dpc, also expressed in the placental blood vessel of embryonic origin (PubMed:11092808).2 Publications

Gene expression databases

BgeeiENSMUSG00000045005
CleanExiMM_FZD5
GenevisibleiQ9EQD0 MM

Interactioni

Subunit structurei

Binding of unsaturated fatty acid molecules (via FZ domain) promotes homodimerization (via FZ domain). Interacts with WNT2B (By similarity). Interacts with WNT7A (PubMed:18230341, PubMed:20530549). Interacts with GOPC (PubMed:11520064).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GopcQ8BH603EBI-7938232,EBI-296357

GO - Molecular functioni

  • protein kinase binding Source: MGI
  • ubiquitin protein ligase binding Source: MGI
  • Wnt-protein binding Source: MGI

Protein-protein interaction databases

BioGridi199778, 1 interactor
DIPiDIP-41260N
IntActiQ9EQD0, 6 interactors
MINTiQ9EQD0
STRINGi10090.ENSMUSP00000067783

Structurei

3D structure databases

ProteinModelPortaliQ9EQD0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 150FZPROSITE-ProRule annotationAdd BLAST123

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi582 – 584PDZ-bindingBy similarity3

Domaini

The PDZ-binding motif mediates interaction with GOPC.By similarity
The FZ domain is involved in binding with Wnt ligands.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000233236
HOVERGENiHBG006977
InParanoidiQ9EQD0
KOiK02375
OMAiVEIHCSP
OrthoDBiEOG091G0N5M
TreeFamiTF317907

Family and domain databases

CDDicd07460 CRD_FZ5, 1 hit
Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR037441 FZ5_CRD
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PfamiView protein in Pfam
PF01534 Frizzled, 1 hit
PF01392 Fz, 1 hit
PRINTSiPR00489 FRIZZLED
SMARTiView protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit
SUPFAMiSSF63501 SSF63501, 1 hit
PROSITEiView 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.

Q9EQD0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARPDPSAPP SLLLLLLAQL VGRAAAASKA PVCQEITVPM CRGIGYNLTH
60 70 80 90 100
MPNQFNHDTQ DEAGLEVHQF WPLVEIHCSP DLRFFLCSMY TPICLPDYHK
110 120 130 140 150
PLPPCRSVCE RAKAGCSPLM RQYGFAWPER MSCDRLPVLG GDAEVLCMDY
160 170 180 190 200
NRSEATTASP KSFPAKPTLP GPPGAPSSGG ECPSGGPSVC TCREPFVPIL
210 220 230 240 250
KESHPLYNKV RTGQVPNCAV PCYQPSFSPD ERTFATFWIG LWSVLCFIST
260 270 280 290 300
STTVATFLID MERFRYPERP IIFLSACYLC VSLGFLVRLV VGHASVACSR
310 320 330 340 350
EHSHIHYETT GPALCTVVFL LVYFFGMASS IWWVILSLTW FLAAGMKWGN
360 370 380 390 400
EAIAGYAQYF HLAAWLIPSV KSITALALSS VDGDPVAGIC YVGNQNLNSL
410 420 430 440 450
RGFVLGPLVL YLLVGTLFLL AGFVSLFRIR SVIKQGGTKT DKLEKLMIRI
460 470 480 490 500
GIFTLLYTVP ASIVVACYLY EQHYRESWEA ALTCACPGPD AGQPRAKPEY
510 520 530 540 550
WVLMLKYFMC LVVGITSGVW IWSGKTLESW RRFTSRCCCS SRRGHKSGGA
560 570 580
MAAGDYAEAS AALTGRTGPP GPTAAYHKQV SLSHV
Length:585
Mass (Da):64,138
Last modified:October 3, 2012 - v3
Checksum:i5FC03620AF087733
GO

Sequence cautioni

The sequence AAG39355 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4P → T in BAC26789 (PubMed:16141072).Curated1
Sequence conflicti123 – 124YG → S in BAC53981 (Ref. 2) Curated2
Sequence conflicti402G → S in AAG39355 (PubMed:11092808).Curated1
Sequence conflicti419L → H in BAC53981 (Ref. 2) Curated1
Sequence conflicti444E → G in BAC53981 (Ref. 2) Curated1
Sequence conflicti477S → T in AAG39355 (PubMed:11092808).Curated1
Sequence conflicti481A → P in AAG39355 (PubMed:11092808).Curated1
Sequence conflicti489P → T in AAG39355 (PubMed:11092808).Curated1
Sequence conflicti521I → F in BAC53981 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF272146 mRNA Translation: AAG39355.1 Frameshift.
AB052910 mRNA Translation: BAC53981.1
AK030111 mRNA Translation: BAC26789.1
AC101915 Genomic DNA No translation available.
CH466548 Genomic DNA Translation: EDL00208.1
CH466548 Genomic DNA Translation: EDL00209.1
AF005203 mRNA Translation: AAC01953.1
CCDSiCCDS15008.1
RefSeqiNP_001036124.1, NM_001042659.1
NP_073558.2, NM_022721.3
UniGeneiMm.150813
Mm.470210

Genome annotation databases

EnsembliENSMUST00000063982; ENSMUSP00000067783; ENSMUSG00000045005
ENSMUST00000116133; ENSMUSP00000111828; ENSMUSG00000045005
GeneIDi14367
KEGGimmu:14367
UCSCiuc007bgy.1 mouse

Similar proteinsi

Entry informationi

Entry nameiFZD5_MOUSE
AccessioniPrimary (citable) accession number: Q9EQD0
Secondary accession number(s): G5E8F0
, O08975, Q8BMR2, Q8CHK9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: October 3, 2012
Last modified: April 25, 2018
This is version 156 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health