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Protein

Frizzled-3

Gene

FZD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner (By similarity).By similarity

GO - Molecular functioni

  • G protein-coupled receptor activity Source: UniProtKB-KW
  • PDZ domain binding Source: UniProtKB
  • Wnt-activated receptor activity Source: GO_Central
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-4086398 Ca2+ pathway
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
SignaLinkiQ9NPG1
SIGNORiQ9NPG1

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-3
Short name:
Fz-3
Short name:
hFz3
Gene namesi
Name:FZD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104290.10
HGNCiHGNC:4041 FZD3
MIMi606143 gene
neXtProtiNX_Q9NPG1

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 domaini23 – 205ExtracellularSequence analysisAdd BLAST183
Transmembranei206 – 226Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini227 – 237CytoplasmicSequence analysisAdd BLAST11
Transmembranei238 – 258Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini259 – 288ExtracellularSequence analysisAdd BLAST30
Transmembranei289 – 309Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini310 – 328CytoplasmicSequence analysisAdd BLAST19
Transmembranei329 – 349Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini350 – 374ExtracellularSequence analysisAdd BLAST25
Transmembranei375 – 395Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini396 – 420CytoplasmicSequence analysisAdd BLAST25
Transmembranei421 – 441Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini442 – 477ExtracellularSequence analysisAdd BLAST36
Transmembranei478 – 498Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini499 – 666CytoplasmicSequence analysisAdd BLAST168

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi7976
OpenTargetsiENSG00000104290
PharmGKBiPA28458

Polymorphism and mutation databases

BioMutaiFZD3
DMDMi17433071

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000001298223 – 666Frizzled-3Add BLAST644

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 89PROSITE-ProRule annotation
Disulfide bondi36 ↔ 82PROSITE-ProRule annotation
Glycosylationi42N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi73 ↔ 110PROSITE-ProRule annotation
Disulfide bondi99 ↔ 133PROSITE-ProRule annotation
Disulfide bondi103 ↔ 127PROSITE-ProRule annotation
Glycosylationi265N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi356N-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

EPDiQ9NPG1
PaxDbiQ9NPG1
PeptideAtlasiQ9NPG1
PRIDEiQ9NPG1
ProteomicsDBi81989

PTM databases

iPTMnetiQ9NPG1
PhosphoSitePlusiQ9NPG1

Expressioni

Tissue specificityi

Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis.

Gene expression databases

BgeeiENSG00000104290 Expressed in 208 organ(s), highest expression level in frontal cortex
CleanExiHS_FZD3
ExpressionAtlasiQ9NPG1 baseline and differential
GenevisibleiQ9NPG1 HS

Organism-specific databases

HPAiCAB024995

Interactioni

Subunit structurei

Interacts with VANGL2.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113689, 9 interactors
IntActiQ9NPG1, 1 interactor
STRINGi9606.ENSP00000240093

Structurei

3D structure databases

ProteinModelPortaliQ9NPG1
SMRiQ9NPG1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 136FZPROSITE-ProRule annotationAdd BLAST114

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi502 – 507Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6

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
HOGENOMiHOG000233237
HOVERGENiHBG006977
InParanoidiQ9NPG1
KOiK02329
OMAiPSIFWVG
OrthoDBiEOG091G0N5M
PhylomeDBiQ9NPG1
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
IPR026553 FZD3_vertebrates
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF22 PTHR11309:SF22, 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

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform Long (identifier: Q9NPG1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAMTWIVFSL WPLTVFMGHI GGHSLFSCEP ITLRMCQDLP YNTTFMPNLL
60 70 80 90 100
NHYDQQTAAL AMEPFHPMVN LDCSRDFRPF LCALYAPICM EYGRVTLPCR
110 120 130 140 150
RLCQRAYSEC SKLMEMFGVP WPEDMECSRF PDCDEPYPRL VDLNLAGEPT
160 170 180 190 200
EGAPVAVQRD YGFWCPRELK IDPDLGYSFL HVRDCSPPCP NMYFRREELS
210 220 230 240 250
FARYFIGLIS IICLSATLFT FLTFLIDVTR FRYPERPIIF YAVCYMMVSL
260 270 280 290 300
IFFIGFLLED RVACNASIPA QYKASTVTQG SHNKACTMLF MILYFFTMAG
310 320 330 340 350
SVWWVILTIT WFLAAVPKWG SEAIEKKALL FHASAWGIPG TLTIILLAMN
360 370 380 390 400
KIEGDNISGV CFVGLYDVDA LRYFVLAPLC LYVVVGVSLL LAGIISLNRV
410 420 430 440 450
RIEIPLEKEN QDKLVKFMIR IGVFSILYLV PLLVVIGCYF YEQAYRGIWE
460 470 480 490 500
TTWIQERCRE YHIPCPYQVT QMSRPDLILF LMKYLMALIV GIPSVFWVGS
510 520 530 540 550
KKTCFEWASF FHGRRKKEIV NESRQVLQEP DFAQSLLRDP NTPIIRKSRG
560 570 580 590 600
TSTQGTSTHA SSTQLAMVDD QRSKAGSIHS KVSSYHGSLH RSRDGRYTPC
610 620 630 640 650
SYRGMEERLP HGSMSRLTDH SRHSSSHRLN EQSRHSSIRD LSNNPMTHIT
660
HGTSMNRVIE EDGTSA
Length:666
Mass (Da):76,263
Last modified:October 1, 2000 - v1
Checksum:i46D7C46E21160215
GO
Isoform Short (identifier: Q9NPG1-2)
Also known as: FZD3deltaC
Sequence is not available
Length:
Mass (Da):

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RGI9E5RGI9_HUMAN
Frizzled-3
FZD3
35Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127C → R in BAF84169 (PubMed:14702039).Curated1
Sequence conflicti402I → V in BAF84169 (PubMed:14702039).Curated1
Sequence conflicti664T → A in BAF84169 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0669604T → S1 PublicationCorresponds to variant dbSNP:rs140115204Ensembl.1
Natural variantiVAR_066961199L → M1 PublicationCorresponds to variant dbSNP:rs757589666Ensembl.1
Natural variantiVAR_066962545I → V1 PublicationCorresponds to variant dbSNP:rs199839949Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB039723 mRNA Translation: BAA94968.1
AJ272427 mRNA Translation: CAB89114.1
AY005130 mRNA Translation: AAF89088.1
AK291480 mRNA Translation: BAF84169.1
CCDSiCCDS6069.1 [Q9NPG1-1]
PIRiJC7312
RefSeqiNP_059108.1, NM_017412.3 [Q9NPG1-1]
NP_665873.1, NM_145866.1 [Q9NPG1-1]
UniGeneiHs.40735
Hs.734277

Genome annotation databases

EnsembliENST00000240093; ENSP00000240093; ENSG00000104290 [Q9NPG1-1]
ENST00000537916; ENSP00000437489; ENSG00000104290 [Q9NPG1-1]
GeneIDi7976
KEGGihsa:7976
UCSCiuc003xgx.4 human [Q9NPG1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB039723 mRNA Translation: BAA94968.1
AJ272427 mRNA Translation: CAB89114.1
AY005130 mRNA Translation: AAF89088.1
AK291480 mRNA Translation: BAF84169.1
CCDSiCCDS6069.1 [Q9NPG1-1]
PIRiJC7312
RefSeqiNP_059108.1, NM_017412.3 [Q9NPG1-1]
NP_665873.1, NM_145866.1 [Q9NPG1-1]
UniGeneiHs.40735
Hs.734277

3D structure databases

ProteinModelPortaliQ9NPG1
SMRiQ9NPG1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113689, 9 interactors
IntActiQ9NPG1, 1 interactor
STRINGi9606.ENSP00000240093

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9NPG1
PhosphoSitePlusiQ9NPG1

Polymorphism and mutation databases

BioMutaiFZD3
DMDMi17433071

Proteomic databases

EPDiQ9NPG1
PaxDbiQ9NPG1
PeptideAtlasiQ9NPG1
PRIDEiQ9NPG1
ProteomicsDBi81989

Protocols and materials databases

DNASUi7976
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000240093; ENSP00000240093; ENSG00000104290 [Q9NPG1-1]
ENST00000537916; ENSP00000437489; ENSG00000104290 [Q9NPG1-1]
GeneIDi7976
KEGGihsa:7976
UCSCiuc003xgx.4 human [Q9NPG1-1]

Organism-specific databases

CTDi7976
DisGeNETi7976
EuPathDBiHostDB:ENSG00000104290.10
GeneCardsiFZD3
HGNCiHGNC:4041 FZD3
HPAiCAB024995
MIMi606143 gene
neXtProtiNX_Q9NPG1
OpenTargetsiENSG00000104290
PharmGKBiPA28458
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000233237
HOVERGENiHBG006977
InParanoidiQ9NPG1
KOiK02329
OMAiPSIFWVG
OrthoDBiEOG091G0N5M
PhylomeDBiQ9NPG1
TreeFamiTF317907

Enzyme and pathway databases

ReactomeiR-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-4086398 Ca2+ pathway
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
SignaLinkiQ9NPG1
SIGNORiQ9NPG1

Miscellaneous databases

ChiTaRSiFZD3 human
GeneWikiiFZD3
GenomeRNAii7976
PROiPR:Q9NPG1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104290 Expressed in 208 organ(s), highest expression level in frontal cortex
CleanExiHS_FZD3
ExpressionAtlasiQ9NPG1 baseline and differential
GenevisibleiQ9NPG1 HS

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
IPR026553 FZD3_vertebrates
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF22 PTHR11309:SF22, 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
ProtoNetiSearch...

Entry informationi

Entry nameiFZD3_HUMAN
AccessioniPrimary (citable) accession number: Q9NPG1
Secondary accession number(s): A8K615
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 155 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  6. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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