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Q13467 (FZD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-5

Short name=Fz-5
Short name=hFz5
Alternative name(s):
FzE5
Gene names
Name:FZD5
Synonyms:C2orf31
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length585 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processWnt signaling pathway
   Cellular componentCell membrane
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSpemann 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 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: Ensembl

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay PubMed 12121999PubMed 12857724. Source: BHF-UCL

cell maturation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

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_componentGolgi 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

early endosome

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionG-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 585559Frizzled-5
PRO_0000012990

Regions

Topological domain27 – 238212Extracellular Potential
Transmembrane239 – 25921Helical; Name=1; Potential
Topological domain260 – 27011Cytoplasmic Potential
Transmembrane271 – 29121Helical; Name=2; Potential
Topological domain292 – 31524Extracellular Potential
Transmembrane316 – 33621Helical; Name=3; Potential
Topological domain337 – 35822Cytoplasmic Potential
Transmembrane359 – 37921Helical; Name=4; Potential
Topological domain380 – 40223Extracellular Potential
Transmembrane403 – 42321Helical; Name=5; Potential
Topological domain424 – 44926Cytoplasmic Potential
Transmembrane450 – 47021Helical; Name=6; Potential
Topological domain471 – 50030Extracellular Potential
Transmembrane501 – 52121Helical; Name=7; Potential
Topological domain522 – 58564Cytoplasmic Potential
Domain28 – 150123FZ
Motif525 – 5306Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif583 – 5853PDZ-binding

Amino acid modifications

Glycosylation471N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Disulfide bond33 ↔ 94 By similarity
Disulfide bond41 ↔ 87 By similarity
Disulfide bond78 ↔ 116 By similarity
Disulfide bond105 ↔ 147 By similarity
Disulfide bond109 ↔ 133 By similarity

Natural variations

Natural variant2161P → L.
Corresponds to variant rs35994626 [ dbSNP | Ensembl ].
VAR_049291

Experimental info

Sequence conflict881S → T in AAC50385. Ref.1
Sequence conflict262 – 2632ER → DT in AAC50385. Ref.1
Sequence conflict3451G → A in AAC50385. Ref.1
Sequence conflict3571A → G in AAC50385. Ref.1
Sequence conflict4021G → R in AAC50385. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q13467 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: AC3AB2CD912C1B0A

FASTA58564,507
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_003459.2. NM_003468.3.
UniGeneHs.17631.

3D structure databases

ProteinModelPortalQ13467.
SMRQ13467. Positions 33-149, 197-532.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113609. 9 interactions.
IntActQ13467. 7 interactions.
MINTMINT-7005936.
STRING9606.ENSP00000354607.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ13467.

Polymorphism databases

DMDM116242481.

Proteomic databases

PaxDbQ13467.
PRIDEQ13467.

Protocols and materials databases

DNASU7855.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295417; ENSP00000354607; ENSG00000163251.
GeneID7855.
KEGGhsa:7855.
UCSCuc002vcj.3. human.

Organism-specific databases

CTD7855.
GeneCardsGC02M208594.
HGNCHGNC:4043. FZD5.
HPAHPA052361.
HPA053811.
MIM601723. gene.
neXtProtNX_Q13467.
PharmGKBPA28460.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidQ13467.
KOK02375.
OMAAATYHKQ.
OrthoDBEOG7M3J01.
PhylomeDBQ13467.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ13467.

Gene expression databases

BgeeQ13467.
CleanExHS_FZD5.
GenevestigatorQ13467.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026547. FZD5/FZD8.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF29. PTHR11309:SF29. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFZD5. human.
GeneWikiFZD5.
GenomeRNAi7855.
NextBio30293.
PROQ13467.
SOURCESearch...

Entry information

Entry nameFZD5_HUMAN
AccessionPrimary (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: February 19, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries