Q13467 (FZD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-5
Short name=Fz-5
Short name=hFz5

Alternative name(s):
FzE5

Gene names

Name:	FZD5
Synonyms:	C2orf31

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	585 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. Interacts specifically with Wnt5A to induce the beta-catenin pathway. Ref.6
Subunit structure	Interacts with GOPC By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Golgi apparatus membrane; Multi-pass membrane protein By similarity. Note: Localized at the plasma membrane and also found at the Golgi By similarity. Ref.6
Domain	The PDZ-binding motif mediates interaction with GOPC By similarity. 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 RNF43 and ZNRF3, leading to its degradation by the proteasome. Ref.7 Ref.8
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 Golgi apparatus 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	Spemann organizer formation Inferred from direct assay Ref.5. Source: BHF-UCL T cell differentiation in thymus Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor signaling pathway involved in dorsal/ventral axis specification Inferred from direct assay PubMed 11029007. Source: BHF-UCL angiogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome anterior/posterior axis specification, embryo Inferred from direct assay Ref.5. Source: BHF-UCL apoptotic process Inferred from Biological aspect of Ancestor. Source: RefGenome apoptotic process involved in morphogenesis Inferred from electronic annotation. Source: Compara 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 12121999PubMed 12857724. Source: BHF-UCL cell maturation Inferred from electronic annotation. Source: Compara cellular response to molecule of bacterial origin Inferred from direct assay PubMed 16601243. Source: BHF-UCL embryonic camera-type eye development Inferred from Biological aspect of Ancestor. Source: RefGenome gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome labyrinthine layer blood vessel development Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma production Inferred from mutant phenotype PubMed 16601243. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12857724. Source: BHF-UCL post-embryonic camera-type eye development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell projection Inferred from Biological aspect of Ancestor. Source: RefGenome cell surface Inferred from direct assay PubMed 19643732. Source: BHF-UCL cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW PDZ domain binding Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt-activated receptor activity Inferred by curator Ref.5. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 585	559	Frizzled-5		PRO_0000012990
Regions
	Topological domain	27 – 238	212	Extracellular Potential
	Transmembrane	239 – 259	21	Helical; Name=1; Potential
	Topological domain	260 – 270	11	Cytoplasmic Potential
	Transmembrane	271 – 291	21	Helical; Name=2; Potential
	Topological domain	292 – 315	24	Extracellular Potential
	Transmembrane	316 – 336	21	Helical; Name=3; Potential
	Topological domain	337 – 358	22	Cytoplasmic Potential
	Transmembrane	359 – 379	21	Helical; Name=4; Potential
	Topological domain	380 – 402	23	Extracellular Potential
	Transmembrane	403 – 423	21	Helical; Name=5; Potential
	Topological domain	424 – 449	26	Cytoplasmic Potential
	Transmembrane	450 – 470	21	Helical; Name=6; Potential
	Topological domain	471 – 500	30	Extracellular Potential
	Transmembrane	501 – 521	21	Helical; Name=7; Potential
	Topological domain	522 – 585	64	Cytoplasmic Potential
	Domain	28 – 150	123	FZ
	Motif	525 – 530	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	583 – 585	3	PDZ-binding
Amino acid modifications
	Glycosylation	47	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Disulfide bond	33 ↔ 94		By similarity
	Disulfide bond	41 ↔ 87		By similarity
	Disulfide bond	78 ↔ 116		By similarity
	Disulfide bond	105 ↔ 147		By similarity
	Disulfide bond	109 ↔ 133		By similarity
Natural variations
	Natural variant	216	1	P → L. Corresponds to variant rs35994626 [ dbSNP | Ensembl ].		VAR_049291
Experimental info
	Sequence conflict	88	1	S → T in AAC50385. Ref.1
	Sequence conflict	262 – 263	2	ER → DT in AAC50385. Ref.1
	Sequence conflict	345	1	G → A in AAC50385. Ref.1
	Sequence conflict	357	1	A → G in AAC50385. Ref.1
	Sequence conflict	402	1	G → R in AAC50385. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q13467 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: AC3AB2CD912C1B0A	FASTA	585	64,507
	10 20 30 40 50 60 MARPDPSAPP SLLLLLLAQL VGRAAAASKA PVCQEITVPM CRGIGYNLTH MPNQFNHDTQ 70 80 90 100 110 120 DEAGLEVHQF WPLVEIQCSP DLRFFLCSMY TPICLPDYHK PLPPCRSVCE RAKAGCSPLM 130 140 150 160 170 180 RQYGFAWPER MSCDRLPVLG RDAEVLCMDY NRSEATTAPP RPFPAKPTLP GPPGAPASGG 190 200 210 220 230 240 ECPAGGPFVC KCREPFVPIL KESHPLYNKV RTGQVPNCAV PCYQPSFSAD ERTFATFWIG 250 260 270 280 290 300 LWSVLCFIST STTVATFLID MERFRYPERP IIFLSACYLC VSLGFLVRLV VGHASVACSR 310 320 330 340 350 360 EHNHIHYETT GPALCTIVFL LVYFFGMASS IWWVILSLTW FLAAGMKWGN EAIAGYAQYF 370 380 390 400 410 420 HLAAWLIPSV KSITALALSS VDGDPVAGIC YVGNQNLNSL RGFVLGPLVL YLLVGTLFLL 430 440 450 460 470 480 AGFVSLFRIR SVIKQGGTKT DKLEKLMIRI GIFTLLYTVP ASIVVACYLY EQHYRESWEA 490 500 510 520 530 540 ALTCACPGHD TGQPRAKPEY WVLMLKYFMC LVVGITSGVW IWSGKTVESW RRFTSRCCCR 550 560 570 580 PRRGHKSGGA MAAGDYPEAS AALTGRTGPP GPAATYHKQV SLSHV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled." Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J. J. Biol. Chem. 271:4468-4476(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[2]	"Molecular cloning and characterization of human Frizzled-5 gene on chromosome 2q33.3-q34 region." Saitoh T., Hirai M., Katoh M. Int. J. Oncol. 19:105-110(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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].
[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 273-331. Tissue: Esophageal carcinoma.
[5]	"A member of the Frizzled protein family mediating axis induction by Wnt-5A." He X., Saint-Jeannet J.P., Wang Y., Nathans J., Dawid I., Varmus H. Science 275:1652-1654(1997) [PubMed] [Europe PMC] [Abstract] Cited for: COUPLING TO BETA-CATENIN PATHWAY.
[6]	"Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein." Hsieh J.C., Rattner A., Smallwood P.M., Nathans J. Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner." Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F. Nature 485:195-200(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY ZNRF3.
[8]	"Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors." Koo B.K., Spit M., Jordens I., Low T.Y., Stange D.E., van de Wetering M., van Es J.H., Mohammed S., Heck A.J., Maurice M.M., Clevers H. Nature 488:665-669(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY RNF43.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U43318 mRNA. Translation: AAC50385.1. AB043702 mRNA. Translation: BAB60959.1. AC096772 Genomic DNA. Translation: AAY24058.1.
IPI	IPI00298743.
RefSeq	NP_003459.2. NM_003468.3.
UniGene	Hs.17631.
3D structure databases
ProteinModelPortal	Q13467.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13467. 5 interactions.
STRING	9606.ENSP00000354607.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q13467.
Polymorphism databases
DMDM	116242481.
Proteomic databases
PaxDb	Q13467.
PRIDE	Q13467.
Protocols and materials databases
DNASU	7855.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295417; ENSP00000354607; ENSG00000163251.
GeneID	7855.
KEGG	hsa:7855.
UCSC	uc002vcj.3. human.
Organism-specific databases
CTD	7855.
GeneCards	GC02M208594.
HGNC	HGNC:4043. FZD5.
HPA	HPA052361. HPA053811.
MIM	601723. gene.
neXtProt	NX_Q13467.
PharmGKB	PA28460.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257258.
HOGENOM	HOG000233236.
HOVERGEN	HBG006977.
InParanoid	Q13467.
KO	K02375.
OMA	PVCQEIT.
OrthoDB	EOG4FFD1K.
PhylomeDB	Q13467.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q13467.
CleanEx	HS_FZD5.
Genevestigator	Q13467.
GermOnline	ENSG00000163251. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026547. FZD5. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF29. PTHR11309:SF29. 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	FZD5. human.
GenomeRNAi	7855.
NextBio	30293.
SOURCE	Search...

Entry information

Entry name

FZD5_HUMAN

Accession

Primary (citable) accession number: Q13467
Secondary accession number(s): Q53R22

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 128 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.