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Protein

Frizzled-1

Gene

FZD1

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

Functioni

Receptor for Wnt proteins (PubMed:10557084). Activated by WNT3A, WNT3, WNT1 and to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6, WNT7A or WNT7B (PubMed:10557084). Contradictory results showing activation by WNT7B have been described for mouse (By similarity). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:10557084). 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:10557084). 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).By similarityCurated1 Publication

Caution

Activation by specific Wnt family members may depend on the cells used for the experiment. Contradictory results have been reported for activation by WNT7B in human and mouse.Curated

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000157240.3
HGNCiHGNC:4038 FZD1
MIMi603408 gene
neXtProtiNX_Q9UP38

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 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

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...) asparagineSequence analysis1
Disulfide bondi161 ↔ 198PROSITE-ProRule annotation
Disulfide bondi187 ↔ 227PROSITE-ProRule annotation
Disulfide bondi191 ↔ 215PROSITE-ProRule annotation
Glycosylationi231N-linked (GlcNAc...) asparagineSequence 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.1 Publication

Gene expression databases

BgeeiENSG00000157240
CleanExiHS_FZD1
GenevisibleiQ9UP38 HS

Organism-specific databases

HPAiCAB013008

Interactioni

Subunit structurei

Interacts with MYOC (PubMed:19188438). Interacts with WNT7B (By similarity).By similarity1 Publication

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • signaling 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
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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR026548 FZD1
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF81 PTHR11309:SF81, 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.

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 dbSNP:rs3750146Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiFZD1_HUMAN
AccessioniPrimary (citable) accession number: Q9UP38
Secondary accession number(s): A4D1E8, O94815, Q549T8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 7, 2006
Last modified: May 23, 2018
This is version 167 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

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

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