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Protein

Frizzled-1

Gene

Fzd1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.

GO - Molecular functioni

  • frizzled binding Source: MGI
  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: MGI
  • receptor binding Source: MGI
  • Wnt-activated receptor activity Source: ParkinsonsUK-UCL
  • Wnt-protein binding Source: MGI

GO - Biological processi

  • autocrine signaling Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation Source: MGI
  • canonical Wnt signaling pathway involved in osteoblast differentiation Source: MGI
  • cell-cell signaling Source: MGI
  • epithelial cell differentiation Source: MGI
  • hard palate development Source: MGI
  • membranous septum morphogenesis Source: MGI
  • muscular septum morphogenesis Source: MGI
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: Ensembl
  • negative regulation of catenin import into nucleus Source: MGI
  • negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCL
  • negative regulation of transcription, DNA-templated Source: MGI
  • outflow tract morphogenesis Source: MGI
  • planar cell polarity pathway involved in neural tube closure Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • response to drug Source: MGI
  • ventricular septum morphogenesis Source: MGI
  • Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-4086400. PCP/CE pathway.
R-MMU-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-1
Short name:
Fz-1
Short name:
mFz1
Gene namesi
Name:Fzd1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1196625. Fzd1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini69 – 317ExtracellularSequence analysisAdd BLAST249
Transmembranei318 – 338Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini339 – 349CytoplasmicSequence analysisAdd BLAST11
Transmembranei350 – 370Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini371 – 397ExtracellularSequence analysisAdd BLAST27
Transmembranei398 – 418Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini419 – 440CytoplasmicSequence analysisAdd BLAST22
Transmembranei441 – 461Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini462 – 484ExtracellularSequence analysisAdd BLAST23
Transmembranei485 – 505Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini506 – 531CytoplasmicSequence analysisAdd BLAST26
Transmembranei532 – 552Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini553 – 593ExtracellularSequence analysisAdd BLAST41
Transmembranei594 – 614Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini615 – 642CytoplasmicSequence analysisAdd BLAST28

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 68Sequence analysisAdd BLAST68
ChainiPRO_000001297469 – 642Frizzled-1Add BLAST574

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi111 ↔ 172PROSITE-ProRule annotation
Disulfide bondi119 ↔ 165PROSITE-ProRule annotation
Glycosylationi125N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi156 ↔ 193PROSITE-ProRule annotation
Disulfide bondi182 ↔ 222PROSITE-ProRule annotation
Disulfide bondi186 ↔ 210PROSITE-ProRule annotation
Glycosylationi226N-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

MaxQBiO70421.
PaxDbiO70421.
PeptideAtlasiO70421.
PRIDEiO70421.

PTM databases

PhosphoSitePlusiO70421.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

BgeeiENSMUSG00000044674.
CleanExiMM_FZD1.
GenevisibleiO70421. MM.

Interactioni

Subunit structurei

Interacts with MYOC.By similarity

GO - Molecular functioni

  • frizzled binding Source: MGI
  • PDZ domain binding Source: MGI
  • receptor binding Source: MGI
  • Wnt-protein binding Source: MGI

Protein-protein interaction databases

BioGridi199775. 3 interactors.
IntActiO70421. 4 interactors.
MINTiMINT-1779162.
STRINGi10090.ENSMUSP00000058629.

Structurei

3D structure databases

ProteinModelPortaliO70421.
SMRiO70421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini106 – 225FZPROSITE-ProRule annotationAdd BLAST120

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi620 – 625Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi640 – 642PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi85 – 90Poly-Pro6

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.
InParanoidiO70421.
KOiK02432.
OMAiWELCAGA.
OrthoDBiEOG091G0N5M.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026548. FZD1.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF81. PTHR11309:SF81. 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.

O70421-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEEAAPSES RAAGRLSLEL CAEALPGRRE EVGHEDTASH RRPRADPRRW
60 70 80 90 100
ASGLLLLLWL LEAPLLLGVR AQAAGQVSGP GQQAPPPPQP QQSGQQYNGE
110 120 130 140 150
RGISIPDHGY CQPISIPLCT DIAYNQTIMP NLLGHTNQED AGLEVHQFYP
160 170 180 190 200
LVKVQCSAEL KFFLCSMYAP VCTVLEQALP PCRSLCERAR QGCEALMNKF
210 220 230 240 250
GFQWPDTLKC EKFPVHGAGE LCVGQNTSDK GTPTPSLLPE FWTSNPQHGG
260 270 280 290 300
GGYRGGYPGG AGTVERGKFS CPRALRVPSY LNYHFLGEKD CGAPCEPTKV
310 320 330 340 350
YGLMYFGPEE LRFSRTWIGI WSVLCCASTL FTVLTYLVDM RRFSYPERPI
360 370 380 390 400
IFLSGCYTAV AVAYIAGFLL EDRVVCNDKF AEDGARTVAQ GTKKEGCTIL
410 420 430 440 450
FMMLYFFSMA SSIWWVILSL TWFLAAGMKW GHEAIEANSQ YFHLAAWAVP
460 470 480 490 500
AIKTITILAL GQVDGDVLSG VCFVGLNNVD ALRGFVLAPL FVYLFIGTSF
510 520 530 540 550
LLAGFVSLFR IRTIMKHDGT KTEKLEKLMV RIGVFSVLYT VPATIVIACY
560 570 580 590 600
FYEQAFRDQW ERSWVAQSCK SYAIPCPHLQ GGGGVPPHPP MSPDFTVFMI
610 620 630 640
KYLMTLIVGI TSGFWIWSGK TLNSWRKFYT RLTNSKQGET TV
Length:642
Mass (Da):71,127
Last modified:July 27, 2011 - v3
Checksum:i7674583F819014E2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti122I → M in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti246P → G in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti341R → P in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti352F → S in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti393K → N in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti474V → L in AAC12873 (PubMed:11334716).Curated1
Sequence conflicti615W → R in AAC12873 (PubMed:11334716).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF054623 mRNA. Translation: AAC12873.2.
AK143101 mRNA. Translation: BAE25269.1.
CH466600 Genomic DNA. Translation: EDL14633.1.
BC053010 mRNA. Translation: AAH53010.1.
AF005202 mRNA. Translation: AAC01952.1.
CCDSiCCDS19072.1.
RefSeqiNP_067432.2. NM_021457.3.
UniGeneiMm.246003.

Genome annotation databases

EnsembliENSMUST00000054294; ENSMUSP00000058629; ENSMUSG00000044674.
GeneIDi14362.
KEGGimmu:14362.
UCSCiuc008wig.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF054623 mRNA. Translation: AAC12873.2.
AK143101 mRNA. Translation: BAE25269.1.
CH466600 Genomic DNA. Translation: EDL14633.1.
BC053010 mRNA. Translation: AAH53010.1.
AF005202 mRNA. Translation: AAC01952.1.
CCDSiCCDS19072.1.
RefSeqiNP_067432.2. NM_021457.3.
UniGeneiMm.246003.

3D structure databases

ProteinModelPortaliO70421.
SMRiO70421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199775. 3 interactors.
IntActiO70421. 4 interactors.
MINTiMINT-1779162.
STRINGi10090.ENSMUSP00000058629.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiO70421.

Proteomic databases

MaxQBiO70421.
PaxDbiO70421.
PeptideAtlasiO70421.
PRIDEiO70421.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000054294; ENSMUSP00000058629; ENSMUSG00000044674.
GeneIDi14362.
KEGGimmu:14362.
UCSCiuc008wig.2. mouse.

Organism-specific databases

CTDi8321.
MGIiMGI:1196625. Fzd1.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiO70421.
KOiK02432.
OMAiWELCAGA.
OrthoDBiEOG091G0N5M.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiR-MMU-4086400. PCP/CE pathway.
R-MMU-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.

Miscellaneous databases

ChiTaRSiFzd1. mouse.
PROiO70421.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044674.
CleanExiMM_FZD1.
GenevisibleiO70421. MM.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026548. FZD1.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF81. PTHR11309:SF81. 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 nameiFZD1_MOUSE
AccessioniPrimary (citable) accession number: O70421
Secondary accession number(s): O08974, Q7TS82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 143 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.