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Protein

Frizzled-5

Gene

FZD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins (PubMed:9054360, PubMed:10097073, PubMed:20530549). 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 (By similarity). In neurons, activation of WNT7A promotes formation of synapses (PubMed:20530549). Functions in the canonical Wnt/beta-catenin signaling pathway. 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 (By similarity). 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 (By similarity).By similarityCurated3 Publications

GO - Molecular functioni

  • amyloid-beta binding Source: ARUK-UCL
  • G-protein coupled receptor activity Source: GO_Central
  • lipid binding Source: UniProtKB-KW
  • protein kinase binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
  • Wnt-activated receptor activity Source: FlyBase
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processWnt signaling pathway
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-4086398 Ca2+ pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-5340588 RNF mutants show enhanced WNT signaling and proliferation
SignaLinkiQ13467
SIGNORiQ13467

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-5
Short name:
Fz-5
Short name:
hFz5
Alternative name(s):
FzE5
Gene namesi
Name:FZD5
Synonyms:C2orf31
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000163251.3
HGNCiHGNC:4043 FZD5
MIMi601723 gene
neXtProtiNX_Q13467

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

Organism-specific databases

DisGeNETi7855
MalaCardsiFZD5
OpenTargetsiENSG00000163251
PharmGKBiPA28460

Chemistry databases

ChEMBLiCHEMBL3559687

Polymorphism and mutation databases

BioMutaiFZD5
DMDMi116242481

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001299027 – 585Frizzled-5Add BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 94PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi41 ↔ 87PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi47N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi78 ↔ 116PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi105 ↔ 147PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi109 ↔ 133PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Ubiquitinated by RNF43 and ZNRF3, leading to its degradation by the proteasome.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

EPDiQ13467
MaxQBiQ13467
PaxDbiQ13467
PeptideAtlasiQ13467
PRIDEiQ13467
ProteomicsDBi59463
TopDownProteomicsiQ13467

PTM databases

iPTMnetiQ13467
PhosphoSitePlusiQ13467

Expressioni

Gene expression databases

BgeeiENSG00000163251
CleanExiHS_FZD5
GenevisibleiQ13467 HS

Organism-specific databases

HPAiHPA052361

Interactioni

Subunit structurei

Binding of unsaturated fatty acid molecules (via FZ domain) promotes homodimerization (PubMed:28377511). Interacts with WNT2B (PubMed:12490564). Interacts with WNT7A (PubMed:18230341, PubMed:20530549). Interacts with GOPC (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SCYL2Q6P3W74EBI-3913027,EBI-1046810

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113609, 13 interactors
IntActiQ13467, 12 interactors
MINTiQ13467
STRINGi9606.ENSP00000354607

Structurei

Secondary structure

1585
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 41Combined sources3
Helixi60 – 67Combined sources8
Helixi68 – 70Combined sources3
Helixi71 – 76Combined sources6
Helixi82 – 90Combined sources9
Helixi106 – 122Combined sources17
Helixi129 – 131Combined sources3
Helixi133 – 135Combined sources3
Turni139 – 141Combined sources3
Beta strandi142 – 144Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5URYX-ray2.10A/B28-155[»]
5URZX-ray2.20A/B28-155[»]
ProteinModelPortaliQ13467
SMRiQ13467
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi525 – 530Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi583 – 585PDZ-binding3

Domaini

The PDZ-binding motif mediates interaction with GOPC.By similarity
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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000233236
HOVERGENiHBG006977
InParanoidiQ13467
KOiK02375
OMAiVEIHCSP
OrthoDBiEOG091G0N5M
PhylomeDBiQ13467
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.

Q13467-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARPDPSAPP SLLLLLLAQL VGRAAAASKA PVCQEITVPM CRGIGYNLTH
60 70 80 90 100
MPNQFNHDTQ DEAGLEVHQF WPLVEIQCSP DLRFFLCSMY TPICLPDYHK
110 120 130 140 150
PLPPCRSVCE RAKAGCSPLM RQYGFAWPER MSCDRLPVLG RDAEVLCMDY
160 170 180 190 200
NRSEATTAPP RPFPAKPTLP GPPGAPASGG ECPAGGPFVC KCREPFVPIL
210 220 230 240 250
KESHPLYNKV RTGQVPNCAV PCYQPSFSAD ERTFATFWIG LWSVLCFIST
260 270 280 290 300
STTVATFLID MERFRYPERP IIFLSACYLC VSLGFLVRLV VGHASVACSR
310 320 330 340 350
EHNHIHYETT GPALCTIVFL 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 ALTCACPGHD TGQPRAKPEY
510 520 530 540 550
WVLMLKYFMC LVVGITSGVW IWSGKTVESW RRFTSRCCCR PRRGHKSGGA
560 570 580
MAAGDYPEAS AALTGRTGPP GPAATYHKQV SLSHV
Length:585
Mass (Da):64,507
Last modified:October 17, 2006 - v2
Checksum:iAC3AB2CD912C1B0A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88S → T in AAC50385 (PubMed:8626800).Curated1
Sequence conflicti262 – 263ER → DT in AAC50385 (PubMed:8626800).Curated2
Sequence conflicti345G → A in AAC50385 (PubMed:8626800).Curated1
Sequence conflicti357A → G in AAC50385 (PubMed:8626800).Curated1
Sequence conflicti384D → G in BAF83075 (PubMed:15815621).Curated1
Sequence conflicti402G → R in AAC50385 (PubMed:8626800).Curated1
Sequence conflicti504M → V in BAG37738 (PubMed:15815621).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049291216P → L. Corresponds to variant dbSNP:rs35994626Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43318 mRNA Translation: AAC50385.1
AB043702 mRNA Translation: BAB60959.1
AK290386 mRNA Translation: BAF83075.1
AK315338 mRNA Translation: BAG37738.1
AC096772 Genomic DNA Translation: AAY24058.1
CCDSiCCDS33366.1
RefSeqiNP_003459.2, NM_003468.3
UniGeneiHs.17631

Genome annotation databases

EnsembliENST00000295417; ENSP00000354607; ENSG00000163251
GeneIDi7855
KEGGihsa:7855
UCSCiuc002vcj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFZD5_HUMAN
AccessioniPrimary (citable) accession number: Q13467
Secondary accession number(s): A8K2X1, B2RCZ1, Q53R22
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 177 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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