Q14332 (FZD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-2
Short name=Fz-2
Short name=hFz2

Alternative name(s):
FzE2

Gene names

Name:

FZD2

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	565 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Widely expressed. In the adult, mainly found in heart, placenta, skeletal muscle, lung, kidney, pancreas, prostate, testis, ovary and colon. In the fetus, expressed in brain, lung and kidney. Low levels in fetal liver.
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
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 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 Wnt receptor signaling pathway, calcium modulating pathway Inferred from Biological aspect of Ancestor. Source: RefGenome axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 20802536. Source: UniProtKB cell-cell signaling Inferred from electronic annotation. Source: Compara cochlea morphogenesis Inferred from electronic annotation. Source: Compara embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome epithelial cell differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome hard palate development Inferred from electronic annotation. Source: Compara inner ear receptor cell development Inferred from electronic annotation. Source: Compara membranous septum morphogenesis Inferred from electronic annotation. Source: Compara muscular septum morphogenesis Inferred from electronic annotation. Source: Compara outflow tract morphogenesis Inferred from electronic annotation. Source: Compara planar cell polarity pathway involved in neural tube closure Inferred from electronic annotation. Source: Compara positive regulation of cGMP metabolic process Inferred from mutant phenotype PubMed 19946729. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18929644. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 18215320PubMed 18929644. Source: BHF-UCL sensory perception of smell 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 cytoplasm Inferred from direct assay PubMed 19038973. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection membrane 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 from Biological aspect of Ancestor. Source: RefGenome Wnt-protein binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 565	542	Frizzled-2		PRO_0000012978
Regions
	Topological domain	24 – 247	224	Extracellular Potential
	Transmembrane	248 – 268	21	Helical; Name=1; Potential
	Topological domain	269 – 279	11	Cytoplasmic Potential
	Transmembrane	280 – 300	21	Helical; Name=2; Potential
	Topological domain	301 – 327	27	Extracellular Potential
	Transmembrane	328 – 348	21	Helical; Name=3; Potential
	Topological domain	349 – 370	22	Cytoplasmic Potential
	Transmembrane	371 – 391	21	Helical; Name=4; Potential
	Topological domain	392 – 414	23	Extracellular Potential
	Transmembrane	415 – 435	21	Helical; Name=5; Potential
	Topological domain	436 – 461	26	Cytoplasmic Potential
	Transmembrane	462 – 482	21	Helical; Name=6; Potential
	Topological domain	483 – 519	37	Extracellular Potential
	Transmembrane	520 – 540	21	Helical; Name=7; Potential
	Topological domain	541 – 565	25	Cytoplasmic Potential
	Domain	34 – 153	120	FZ
	Motif	543 – 548	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	563 – 565	3	PDZ-binding
	Compositional bias	181 – 187	7	Poly-Gly
Amino acid modifications
	Glycosylation	53	1	N-linked (GlcNAc...) Potential
	Glycosylation	154	1	N-linked (GlcNAc...) Potential
	Disulfide bond	39 ↔ 100		By similarity
	Disulfide bond	47 ↔ 93		By similarity
	Disulfide bond	84 ↔ 121		By similarity
	Disulfide bond	110 ↔ 150		By similarity
	Disulfide bond	114 ↔ 138		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q14332 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: AA387876A1DDE063	FASTA	565	63,554
	10 20 30 40 50 60 MRPRSALPRL LLPLLLLPAA GPAQFHGEKG ISIPDHGFCQ PISIPLCTDI AYNQTIMPNL 70 80 90 100 110 120 LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC TVLEQAIPPC RSICERARQG 130 140 150 160 170 180 CEALMNKFGF QWPERLRCEH FPRHGAEQIC VGQNHSEDGA PALLTTAPPP GLQPGAGGTP 190 200 210 220 230 240 GGPGGGGAPP RYATLEHPFH CPRVLKVPSY LSYKFLGERD CAAPCEPARP DGSMFFSQEE 250 260 270 280 290 300 TRFARLWILT WSVLCCASTF FTVTTYLVDM QRFRYPERPI IFLSGCYTMV SVAYIAGFVL 310 320 330 340 350 360 QERVVCNERF SEDGYRTVVQ GTKKEGCTIL FMMLYFFSMA SSIWWVILSL TWFLAAGMKW 370 380 390 400 410 420 GHEAIEANSQ YFHLAAWAVP AVKTITILAM GQIDGDLLSG VCFVGLNSLD PLRGFVLAPL 430 440 450 460 470 480 FVYLFIGTSF LLAGFVSLFR IRTIMKHDGT KTEKLERLMV RIGVFSVLYT VPATIVIACY 490 500 510 520 530 540 FYEQAFREHW ERSWVSQHCK SLAIPCPAHY TPRMSPDFTV YMIKYLMTLI VGITSGFWIW 550 560 SGKTLHSWRK FYTRLTNSRH GETTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1." Zhao Z., Lee C.C., Baldini A., Caskey C.T. Genomics 27:370-373(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[2]	"Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7." Sagara N., Toda G., Hirai M., Terada M., Katoh M. Biochem. Biophys. Res. Commun. 252:117-122(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal lung.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals." Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K. Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 282-343. Tissue: Esophageal carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L37882 mRNA. Translation: AAB46397.1. AB017364 mRNA. Translation: BAA34667.1. BC113402 mRNA. Translation: AAI13403.1. BC113404 mRNA. Translation: AAI13405.1.
IPI	IPI00016027.
PIR	JE0338.
RefSeq	NP_001457.1. NM_001466.3.
UniGene	Hs.142912. Hs.732654.
3D structure databases
ProteinModelPortal	Q14332.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14332. 1 interaction.
STRING	9606.ENSP00000323901.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q14332.
Polymorphism databases
DMDM	17433019.
Proteomic databases
PaxDb	Q14332.
PRIDE	Q14332.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315323; ENSP00000323901; ENSG00000180340.
GeneID	2535.
KEGG	hsa:2535.
UCSC	uc002igx.2. human.
Organism-specific databases
CTD	2535.
GeneCards	GC17P042645.
HGNC	HGNC:4040. FZD2.
MIM	600667. gene.
neXtProt	NX_Q14332.
PharmGKB	PA28457.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257258.
HOVERGEN	HBG006977.
InParanoid	Q14332.
KO	K02235.
OrthoDB	EOG4V437C.
PhylomeDB	Q14332.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q14332.
Bgee	Q14332.
CleanEx	HS_FZD2.
Genevestigator	Q14332.
GermOnline	ENSG00000180340. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026550. FZD2. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF34. PTHR11309:SF34. 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	FZD2. human.
GenomeRNAi	2535.
NextBio	10005.
SOURCE	Search...

Entry information

Entry name

FZD2_HUMAN

Accession

Primary (citable) accession number: Q14332
Secondary accession number(s): Q0VG82

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 118 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.