O75084 (FZD7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-7
Short name=Fz-7
Short name=hFz7

Alternative name(s):
FzE3

Gene names

Name:

FZD7

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	574 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.
Subunit structure	Interacts with MAGI3 and DVL1 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein By similarity. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	High expression in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. Specifically expressed in squamous cell esophageal carcinomas.
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	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 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 T cell differentiation in thymus Inferred from electronic annotation. Source: Compara 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 cellular response to retinoic acid Inferred from sequence or structural similarity. Source: UniProtKB gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome mesenchymal to epithelial transition Inferred from mutant phenotype PubMed 17016432. Source: BHF-UCL negative regulation of cell-substrate adhesion Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL negative regulation of ectodermal cell fate specification Inferred from mutant phenotype PubMed 18681827. Source: BHF-UCL non-canonical Wnt receptor signaling pathway via JNK cascade Inferred from mutant phenotype PubMed 19773752. Source: BHF-UCL positive regulation of JNK cascade Inferred by curator PubMed 18256285. Source: BHF-UCL positive regulation of epithelial cell proliferation involved in wound healing Inferred from mutant phenotype PubMed 18313787. Source: BHF-UCL positive regulation of phosphorylation Inferred from direct assay PubMed 18256285. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 18215320. Source: BHF-UCL regulation of catenin import into nucleus Inferred from mutant phenotype Ref.1. Source: BHF-UCL satellite cell maintenance involved in skeletal muscle regeneration Inferred from electronic annotation. Source: Compara somatic stem cell division Inferred from electronic annotation. Source: Compara stem cell maintenance Inferred from mutant phenotype PubMed 18681827. Source: BHF-UCL substrate adhesion-dependent cell spreading 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 Biological aspect of Ancestor. Source: RefGenome integral to membrane Traceable author statement Ref.1. Source: BHF-UCL 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Potential
	Chain	33 – 574	542	Frizzled-7		PRO_0000012996
Regions
	Topological domain	33 – 256	224	Extracellular Potential
	Transmembrane	257 – 277	21	Helical; Name=1; Potential
	Topological domain	278 – 288	11	Cytoplasmic Potential
	Transmembrane	289 – 309	21	Helical; Name=2; Potential
	Topological domain	310 – 336	27	Extracellular Potential
	Transmembrane	337 – 357	21	Helical; Name=3; Potential
	Topological domain	358 – 379	22	Cytoplasmic Potential
	Transmembrane	380 – 400	21	Helical; Name=4; Potential
	Topological domain	401 – 423	23	Extracellular Potential
	Transmembrane	424 – 444	21	Helical; Name=5; Potential
	Topological domain	445 – 470	26	Cytoplasmic Potential
	Transmembrane	471 – 491	21	Helical; Name=6; Potential
	Topological domain	492 – 528	37	Extracellular Potential
	Transmembrane	529 – 549	21	Helical; Name=7; Potential
	Topological domain	550 – 574	25	Cytoplasmic Potential
	Domain	44 – 163	120	FZ
	Motif	552 – 557	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	572 – 574	3	PDZ-binding
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Disulfide bond	49 ↔ 110		By similarity
	Disulfide bond	57 ↔ 103		By similarity
	Disulfide bond	94 ↔ 131		By similarity
	Disulfide bond	120 ↔ 160		By similarity
	Disulfide bond	124 ↔ 148		By similarity
Natural variations
	Natural variant	24	1	G → D. Corresponds to variant rs35111363 [ dbSNP | Ensembl ].		VAR_049292
	Natural variant	24	1	G → S. Ref.6		VAR_033024
	Natural variant	196	1	G → E. Corresponds to variant rs34908164 [ dbSNP | Ensembl ].		VAR_033941
	Natural variant	487	1	A → V. Corresponds to variant rs35600847 [ dbSNP | Ensembl ].		VAR_033942
Experimental info
	Sequence conflict	8	1	A → V in BAA32424. Ref.1
	Sequence conflict	15	1	L → F in BAA32424. Ref.1
	Sequence conflict	201	1	R → K in BAA32424. Ref.1
	Sequence conflict	308	1	L → F in BAA32424. Ref.1
	Sequence conflict	408	1	S → N in BAA32424. Ref.1
	Sequence conflict	415	1	L → F in BAA32424. Ref.1
	Sequence conflict	433	1	L → F in BAA32424. Ref.1
	Sequence conflict	447	1	L → F in BAA32424. Ref.1
	Sequence conflict	534	1	Y → C in BAA32424. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75084 [UniParc]. Last modified September 27, 2004. Version 2. Checksum: 801934246B426DF5	FASTA	574	63,620
	10 20 30 40 50 60 MRDPGAAAPL SSLGLCALVL ALLGALSAGA GAQPYHGEKG ISVPDHGFCQ PISIPLCTDI 70 80 90 100 110 120 AYNQTILPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC TVLDQAIPPC 130 140 150 160 170 180 RSLCERARQG CEALMNKFGF QWPERLRCEN FPVHGAGEIC VGQNTSDGSG GPGGGPTAYP 190 200 210 220 230 240 TAPYLPDLPF TALPPGASDG RGRPAFPFSC PRQLKVPPYL GYRFLGERDC GAPCEPGRAN 250 260 270 280 290 300 GLMYFKEEER RFARLWVGVW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYFMVA 310 320 330 340 350 360 VAHVAGFLLE DRAVCVERFS DDGYRTVAQG TKKEGCTILF MVLYFFGMAS SIWWVILSLT 370 380 390 400 410 420 WFLAAGMKWG HEAIEANSQY FHLAAWAVPA VKTITILAMG QVDGDLLSGV CYVGLSSVDA 430 440 450 460 470 480 LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV 490 500 510 520 530 540 PATIVLACYF YEQAFREHWE RTWLLQTCKS YAVPCPPGHF PPMSPDFTVF MIKYLMTMIV 550 560 570 GITTGFWIWS GKTLQSWRRF YHRLSHSSKG ETAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], COUPLING TO BETA-CATENIN PATHWAY. Tissue: Esophageal carcinoma.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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.
[5]	"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]. Tissue: Lung.
[6]	"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas." Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L. Breast Cancer Res. 9:R5-R5(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-24.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB010881 mRNA. Translation: BAA32424.1. AB017365 mRNA. Translation: BAA34668.1. AC069148 Genomic DNA. Translation: AAX93250.1. CH471063 Genomic DNA. Translation: EAW70298.1. BC015915 mRNA. Translation: AAH15915.1.
IPI	IPI00024012.
PIR	JE0339.
RefSeq	NP_003498.1. NM_003507.1.
UniGene	Hs.173859.
3D structure databases
ProteinModelPortal	O75084.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75084. 4 interactions.
MINT	MINT-1461434.
STRING	9606.ENSP00000286201.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O75084.
Proteomic databases
PaxDb	O75084.
PRIDE	O75084.
Protocols and materials databases
DNASU	8324.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286201; ENSP00000286201; ENSG00000155760.
GeneID	8324.
KEGG	hsa:8324.
UCSC	uc002uyw.1. human.
Organism-specific databases
CTD	8324.
GeneCards	GC02P202863.
HGNC	HGNC:4045. FZD7.
MIM	603410. gene.
neXtProt	NX_O75084.
PharmGKB	PA28462.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257258.
HOGENOM	HOG000233237.
HOVERGEN	HBG006977.
InParanoid	O75084.
KO	K02432.
OMA	CVERFSE.
OrthoDB	EOG4V437C.
PhylomeDB	O75084.
Enzyme and pathway databases
Pathway_Interaction_DB	syndecan_4_pathway. Syndecan-4-mediated signaling events.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	O75084.
CleanEx	HS_FZD7.
Genevestigator	O75084.
GermOnline	ENSG00000155760. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026552. FZD7. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF31. PTHR11309:SF31. 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	FZD7. human.
GenomeRNAi	8324.
NextBio	31171.
SOURCE	Search...

Entry information

Entry name

FZD7_HUMAN

Accession

Primary (citable) accession number: O75084
Secondary accession number(s): O94816, Q53S59, Q96B74

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	September 27, 2004
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 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.