Q9NPG1 (FZD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-3
Short name=Fz-3
Short name=hFz3

Gene names

Name:

FZD3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	666 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Interacts with VANGL2 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis.
Domain	Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman 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.
Post-translational modification	Ubiquitinated by ZNRF3, leading to its degradation by the proteasome By similarity.
Sequence similarities	Belongs to the G-protein coupled receptor Fz/Smo family. Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 20802536. Source: UniProtKB cell proliferation in midbrain Inferred from Biological aspect of Ancestor. Source: RefGenome commissural neuron axon guidance Inferred from Biological aspect of Ancestor. Source: RefGenome establishment of planar polarity Inferred from Biological aspect of Ancestor. Source: RefGenome facial nucleus development Inferred from Biological aspect of Ancestor. Source: RefGenome gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome hair follicle development Inferred from electronic annotation. Source: Compara inner ear morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome neural tube closure Inferred from Biological aspect of Ancestor. Source: RefGenome neuron migration Inferred from electronic annotation. Source: Compara post-anal tail morphogenesis Inferred from electronic annotation. Source: Compara vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	apical part of cell Inferred from Biological aspect of Ancestor. Source: RefGenome apical plasma membrane Inferred from electronic annotation. Source: Compara axon Inferred from Biological aspect of Ancestor. Source: RefGenome cytoplasm Inferred from direct assay PubMed 19038973. Source: BHF-UCL dendrite Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection membrane Inferred from Biological aspect of Ancestor. Source: RefGenome neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome presynaptic active zone Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW Wnt-activated receptor activity Inferred by curator PubMed 19038973. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]

Isoform Long (identifier: Q9NPG1-1)

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.

Isoform Short (identifier: Q9NPG1-2)

Also known as: FZD3deltaC;

The sequence of this isoform is not available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Ref.4
	Chain	23 – 666	644	Frizzled-3		PRO_0000012982
Regions
	Topological domain	23 – 205	183	Extracellular Potential
	Transmembrane	206 – 226	21	Helical; Name=1; Potential
	Topological domain	227 – 237	11	Cytoplasmic Potential
	Transmembrane	238 – 258	21	Helical; Name=2; Potential
	Topological domain	259 – 288	30	Extracellular Potential
	Transmembrane	289 – 309	21	Helical; Name=3; Potential
	Topological domain	310 – 328	19	Cytoplasmic Potential
	Transmembrane	329 – 349	21	Helical; Name=4; Potential
	Topological domain	350 – 374	25	Extracellular Potential
	Transmembrane	375 – 395	21	Helical; Name=5; Potential
	Topological domain	396 – 420	25	Cytoplasmic Potential
	Transmembrane	421 – 441	21	Helical; Name=6; Potential
	Topological domain	442 – 477	36	Extracellular Potential
	Transmembrane	478 – 498	21	Helical; Name=7; Potential
	Topological domain	499 – 666	168	Cytoplasmic Potential
	Domain	23 – 136	114	FZ
	Motif	502 – 507	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Amino acid modifications
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Glycosylation	356	1	N-linked (GlcNAc...) Potential
	Disulfide bond	28 ↔ 89		By similarity
	Disulfide bond	36 ↔ 82		By similarity
	Disulfide bond	73 ↔ 110		By similarity
	Disulfide bond	99 ↔ 133		By similarity
	Disulfide bond	103 ↔ 127		By similarity
Natural variations
	Natural variant	4	1	T → S. Ref.5 Corresponds to variant rs140115204 [ dbSNP | Ensembl ].		VAR_066960
	Natural variant	199	1	L → M. Ref.5		VAR_066961
	Natural variant	545	1	I → V. Ref.5		VAR_066962

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 46D7C46E21160215	FASTA	666	76,263
	10 20 30 40 50 60 MAMTWIVFSL WPLTVFMGHI GGHSLFSCEP ITLRMCQDLP YNTTFMPNLL NHYDQQTAAL 70 80 90 100 110 120 AMEPFHPMVN LDCSRDFRPF LCALYAPICM EYGRVTLPCR RLCQRAYSEC SKLMEMFGVP 130 140 150 160 170 180 WPEDMECSRF PDCDEPYPRL VDLNLAGEPT EGAPVAVQRD YGFWCPRELK IDPDLGYSFL 190 200 210 220 230 240 HVRDCSPPCP NMYFRREELS FARYFIGLIS IICLSATLFT FLTFLIDVTR FRYPERPIIF 250 260 270 280 290 300 YAVCYMMVSL IFFIGFLLED RVACNASIPA QYKASTVTQG SHNKACTMLF MILYFFTMAG 310 320 330 340 350 360 SVWWVILTIT WFLAAVPKWG SEAIEKKALL FHASAWGIPG TLTIILLAMN KIEGDNISGV 370 380 390 400 410 420 CFVGLYDVDA LRYFVLAPLC LYVVVGVSLL LAGIISLNRV RIEIPLEKEN QDKLVKFMIR 430 440 450 460 470 480 IGVFSILYLV PLLVVIGCYF YEQAYRGIWE TTWIQERCRE YHIPCPYQVT QMSRPDLILF 490 500 510 520 530 540 LMKYLMALIV GIPSVFWVGS KKTCFEWASF FHGRRKKEIV NESRQVLQEP DFAQSLLRDP 550 560 570 580 590 600 NTPIIRKSRG TSTQGTSTHA SSTQLAMVDD QRSKAGSIHS KVSSYHGSLH RSRDGRYTPC 610 620 630 640 650 660 SYRGMEERLP HGSMSRLTDH SRHSSSHRLN EQSRHSSIRD LSNNPMTHIT HGTSMNRVIE EDGTSA
	Isoform Short (FZD3deltaC) (Sequence not available).		–	–

References

[1]	"Molecular cloning and genomic structure of human frizzled-3 at chromosome 8p21." Kirikoshi H., Koike J., Sagara N., Saitoh T., Tokuhara M., Tanaka K., Sekihara H., Hirai M., Katoh M. Biochem. Biophys. Res. Commun. 271:8-14(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"Identification, gene structure and expression of human frizzled-3 (FZD3)." Sala C.F., Formenti E., Terstappen G.C., Caricasole A. Biochem. Biophys. Res. Commun. 273:27-34(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[3]	"Characterization of mouse frizzled-3 expression in hair follicle development and identification of the human homolog in keratinocytes." Hung B.S., Wang X.-Q., Cam G.R., Rothnagel J.A. J. Invest. Dermatol. 116:940-946(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Keratinocyte.
[4]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37.
[5]	"FZD6 is a novel gene for human neural tube defects." De Marco P., Merello E., Rossi A., Piatelli G., Cama A., Kibar Z., Capra V. Hum. Mutat. 33:384-390(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-4; MET-199 AND VAL-545.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB039723 mRNA. Translation: BAA94968.1. AJ272427 mRNA. Translation: CAB89114.1. AY005130 mRNA. Translation: AAF89088.1.
IPI	IPI00424119.
PIR	JC7312.
RefSeq	NP_059108.1. NM_017412.3. NP_665873.1. NM_145866.1.
UniGene	Hs.40735. Hs.734277.
3D structure databases
ProteinModelPortal	Q9NPG1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000240093.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9NPG1.
Polymorphism databases
DMDM	17433071.
Proteomic databases
PaxDb	Q9NPG1.
PRIDE	Q9NPG1.
Protocols and materials databases
DNASU	7976.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000240093; ENSP00000240093; ENSG00000104290. ENST00000537916; ENSP00000437489; ENSG00000104290.
GeneID	7976.
KEGG	hsa:7976.
UCSC	uc003xgx.3. human.
Organism-specific databases
CTD	7976.
GeneCards	GC08P028351.
HGNC	HGNC:4041. FZD3.
HPA	CAB024995.
MIM	606143. gene.
neXtProt	NX_Q9NPG1.
PharmGKB	PA28458.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG259824.
HOGENOM	HOG000233237.
HOVERGEN	HBG006977.
InParanoid	Q9NPG1.
KO	K02329.
OMA	LTMFVGH.
OrthoDB	EOG4PVNZ5.
PhylomeDB	Q9NPG1.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_calcium_pathway. Noncanonical Wnt signaling pathway. wnt_signaling_pathway. Wnt signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9NPG1.
Bgee	Q9NPG1.
CleanEx	HS_FZD3.
Genevestigator	Q9NPG1.
GermOnline	ENSG00000104290. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026553. FZD3_chordata. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF22. PTHR11309:SF22. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FZD3. human.
GenomeRNAi	7976.
NextBio	30495.
SOURCE	Search...

Entry information

Entry name

FZD3_HUMAN

Accession

Primary (citable) accession number: Q9NPG1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.