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Protein

Frizzled-5

Gene

FZD5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Interacts specifically with Wnt5A to induce the beta-catenin pathway.1 Publication

GO - Molecular functioni

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

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

BioCyciZFISH:ENSG00000163251-MONOMER.
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

HGNCiHGNC:4043. FZD5.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi7855.
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 annotation
Disulfide bondi41 ↔ 87PROSITE-ProRule annotation
Glycosylationi47N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi78 ↔ 116PROSITE-ProRule annotation
Disulfide bondi105 ↔ 147PROSITE-ProRule annotation
Disulfide bondi109 ↔ 133PROSITE-ProRule annotation
Glycosylationi151N-linked (GlcNAc...)Sequence 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.
TopDownProteomicsiQ13467.

PTM databases

iPTMnetiQ13467.
PhosphoSitePlusiQ13467.

Expressioni

Gene expression databases

BgeeiENSG00000163251.
CleanExiHS_FZD5.
GenevisibleiQ13467. HS.

Organism-specific databases

HPAiHPA052361.
HPA053811.

Interactioni

Subunit structurei

Interacts with GOPC.By similarity

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.
MINTiMINT-7005936.
STRINGi9606.ENSP00000354607.

Structurei

3D structure databases

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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ13467.
KOiK02375.
OMAiPICLPEY.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ13467.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026547. FZD5.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF91. PTHR11309:SF91. 1 hit.
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.

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 rs35994626dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ13467.
SMRiQ13467.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113609. 13 interactors.
IntActiQ13467. 12 interactors.
MINTiMINT-7005936.
STRINGi9606.ENSP00000354607.

Chemistry databases

ChEMBLiCHEMBL3559687.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ13467.
PhosphoSitePlusiQ13467.

Polymorphism and mutation databases

BioMutaiFZD5.
DMDMi116242481.

Proteomic databases

EPDiQ13467.
MaxQBiQ13467.
PaxDbiQ13467.
PeptideAtlasiQ13467.
PRIDEiQ13467.
TopDownProteomicsiQ13467.

Protocols and materials databases

DNASUi7855.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7855.
DisGeNETi7855.
GeneCardsiFZD5.
HGNCiHGNC:4043. FZD5.
HPAiHPA052361.
HPA053811.
MIMi601723. gene.
neXtProtiNX_Q13467.
OpenTargetsiENSG00000163251.
PharmGKBiPA28460.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ13467.
KOiK02375.
OMAiPICLPEY.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ13467.
TreeFamiTF317907.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163251-MONOMER.
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.

Miscellaneous databases

ChiTaRSiFZD5. human.
GeneWikiiFZD5.
GenomeRNAii7855.
PROiQ13467.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163251.
CleanExiHS_FZD5.
GenevisibleiQ13467. HS.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026547. FZD5.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF91. PTHR11309:SF91. 1 hit.
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 nameiFZD5_HUMAN
AccessioniPrimary (citable) accession number: Q13467
Secondary accession number(s): A8K2X1, B2RCZ1, Q53R22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 162 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.