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Protein

Frizzled-1

Gene

FZD1

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. Activated by Wnt3A, Wnt3, Wnt1 and to a lesser extent Wnt2, but not by Wnt4, Wnt5A, Wnt5B, Wnt6, Wnt7A or Wnt7B.

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: UniProtKB
  • receptor binding Source: BHF-UCL
  • 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:ENSG00000157240-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-4086400. PCP/CE pathway.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
SignaLinkiQ9UP38.
SIGNORiQ9UP38.

Protein family/group databases

TCDBi9.A.14.16.1. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-1
Short name:
Fz-1
Short name:
hFz1
Alternative name(s):
FzE1
Gene namesi
Name:FZD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4038. FZD1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini73 – 322ExtracellularSequence analysisAdd BLAST250
Transmembranei323 – 343Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini344 – 354CytoplasmicSequence analysisAdd BLAST11
Transmembranei355 – 375Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini376 – 402ExtracellularSequence analysisAdd BLAST27
Transmembranei403 – 423Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini424 – 445CytoplasmicSequence analysisAdd BLAST22
Transmembranei446 – 466Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini467 – 489ExtracellularSequence analysisAdd BLAST23
Transmembranei490 – 510Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini511 – 536CytoplasmicSequence analysisAdd BLAST26
Transmembranei537 – 557Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini558 – 601ExtracellularSequence analysisAdd BLAST44
Transmembranei602 – 622Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini623 – 647CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • focal adhesion Source: UniProtKB
  • integral component of membrane Source: GO_Central
  • plasma membrane Source: Reactome
  • Wnt signalosome Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8321.
OpenTargetsiENSG00000157240.
PharmGKBiPA28455.

Chemistry databases

ChEMBLiCHEMBL2346493.

Polymorphism and mutation databases

BioMutaiFZD1.
DMDMi92058705.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 69Sequence analysisAdd BLAST69
ChainiPRO_000001297370 – 647Frizzled-1Add BLAST578

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi116 ↔ 177PROSITE-ProRule annotation
Disulfide bondi124 ↔ 170PROSITE-ProRule annotation
Glycosylationi130N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi161 ↔ 198PROSITE-ProRule annotation
Disulfide bondi187 ↔ 227PROSITE-ProRule annotation
Disulfide bondi191 ↔ 215PROSITE-ProRule annotation
Glycosylationi231N-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

EPDiQ9UP38.
MaxQBiQ9UP38.
PaxDbiQ9UP38.
PeptideAtlasiQ9UP38.
PRIDEiQ9UP38.

PTM databases

iPTMnetiQ9UP38.
PhosphoSitePlusiQ9UP38.

Expressioni

Tissue specificityi

Expressed in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary and in fetal lung and kidney.

Gene expression databases

BgeeiENSG00000157240.
CleanExiHS_FZD1.
GenevisibleiQ9UP38. HS.

Organism-specific databases

HPAiCAB013008.

Interactioni

Subunit structurei

Interacts with MYOC.1 Publication

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • receptor binding Source: BHF-UCL
  • Wnt-protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113917. 11 interactors.
IntActiQ9UP38. 8 interactors.
STRINGi9606.ENSP00000287934.

Structurei

3D structure databases

ProteinModelPortaliQ9UP38.
SMRiQ9UP38.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini111 – 230FZPROSITE-ProRule annotationAdd BLAST120

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi625 – 630Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi645 – 647PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi89 – 93Poly-Pro5

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.
InParanoidiQ9UP38.
KOiK02432.
OMAiWELCAGA.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ9UP38.
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. 2 hits.
PTHR11309:SF81. PTHR11309:SF81. 2 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.

Q9UP38-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEEEAPKKS RAAGGGASWE LCAGALSARL AEEGSGDAGG RRRPPVDPRR
60 70 80 90 100
LARQLLLLLW LLEAPLLLGV RAQAAGQGPG QGPGPGQQPP PPPQQQQSGQ
110 120 130 140 150
QYNGERGISV PDHGYCQPIS IPLCTDIAYN QTIMPNLLGH TNQEDAGLEV
160 170 180 190 200
HQFYPLVKVQ CSAELKFFLC SMYAPVCTVL EQALPPCRSL CERARQGCEA
210 220 230 240 250
LMNKFGFQWP DTLKCEKFPV HGAGELCVGQ NTSDKGTPTP SLLPEFWTSN
260 270 280 290 300
PQHGGGGHRG GFPGGAGASE RGKFSCPRAL KVPSYLNYHF LGEKDCGAPC
310 320 330 340 350
EPTKVYGLMY FGPEELRFSR TWIGIWSVLC CASTLFTVLT YLVDMRRFSY
360 370 380 390 400
PERPIIFLSG CYTAVAVAYI AGFLLEDRVV CNDKFAEDGA RTVAQGTKKE
410 420 430 440 450
GCTILFMMLY FFSMASSIWW VILSLTWFLA AGMKWGHEAI EANSQYFHLA
460 470 480 490 500
AWAVPAIKTI TILALGQVDG DVLSGVCFVG LNNVDALRGF VLAPLFVYLF
510 520 530 540 550
IGTSFLLAGF VSLFRIRTIM KHDGTKTEKL EKLMVRIGVF SVLYTVPATI
560 570 580 590 600
VIACYFYEQA FRDQWERSWV AQSCKSYAIP CPHLQAGGGA PPHPPMSPDF
610 620 630 640
TVFMIKYLMT LIVGITSGFW IWSGKTLNSW RKFYTRLTNS KQGETTV
Length:647
Mass (Da):71,158
Last modified:March 7, 2006 - v2
Checksum:i7FC916A736482826
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti93P → PP in AAD41636 (PubMed:10557084).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049290343V → M.Corresponds to variant rs3750146dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072872 mRNA. Translation: AAD41636.1.
AB017363 mRNA. Translation: BAA34666.1.
AC084381 Genomic DNA. Translation: AAS02008.1.
CH236949 Genomic DNA. Translation: EAL24161.1.
CH471091 Genomic DNA. Translation: EAW76871.1.
BC051271 mRNA. Translation: AAH51271.1.
CCDSiCCDS5620.1.
PIRiJE0337.
RefSeqiNP_003496.1. NM_003505.1.
UniGeneiHs.94234.

Genome annotation databases

EnsembliENST00000287934; ENSP00000287934; ENSG00000157240.
GeneIDi8321.
KEGGihsa:8321.
UCSCiuc003ula.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072872 mRNA. Translation: AAD41636.1.
AB017363 mRNA. Translation: BAA34666.1.
AC084381 Genomic DNA. Translation: AAS02008.1.
CH236949 Genomic DNA. Translation: EAL24161.1.
CH471091 Genomic DNA. Translation: EAW76871.1.
BC051271 mRNA. Translation: AAH51271.1.
CCDSiCCDS5620.1.
PIRiJE0337.
RefSeqiNP_003496.1. NM_003505.1.
UniGeneiHs.94234.

3D structure databases

ProteinModelPortaliQ9UP38.
SMRiQ9UP38.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113917. 11 interactors.
IntActiQ9UP38. 8 interactors.
STRINGi9606.ENSP00000287934.

Chemistry databases

ChEMBLiCHEMBL2346493.

Protein family/group databases

TCDBi9.A.14.16.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiQ9UP38.
PhosphoSitePlusiQ9UP38.

Polymorphism and mutation databases

BioMutaiFZD1.
DMDMi92058705.

Proteomic databases

EPDiQ9UP38.
MaxQBiQ9UP38.
PaxDbiQ9UP38.
PeptideAtlasiQ9UP38.
PRIDEiQ9UP38.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287934; ENSP00000287934; ENSG00000157240.
GeneIDi8321.
KEGGihsa:8321.
UCSCiuc003ula.4. human.

Organism-specific databases

CTDi8321.
DisGeNETi8321.
GeneCardsiFZD1.
HGNCiHGNC:4038. FZD1.
HPAiCAB013008.
MIMi603408. gene.
neXtProtiNX_Q9UP38.
OpenTargetsiENSG00000157240.
PharmGKBiPA28455.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9UP38.
KOiK02432.
OMAiWELCAGA.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ9UP38.
TreeFamiTF317907.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000157240-MONOMER.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-4086400. PCP/CE pathway.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
SignaLinkiQ9UP38.
SIGNORiQ9UP38.

Miscellaneous databases

ChiTaRSiFZD1. human.
GeneWikiiFZD1.
GenomeRNAii8321.
PROiQ9UP38.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157240.
CleanExiHS_FZD1.
GenevisibleiQ9UP38. HS.

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. 2 hits.
PTHR11309:SF81. PTHR11309:SF81. 2 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 nameiFZD1_HUMAN
AccessioniPrimary (citable) accession number: Q9UP38
Secondary accession number(s): A4D1E8, O94815, Q549T8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 7, 2006
Last modified: November 30, 2016
This is version 154 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 7
    Human chromosome 7: 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.