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Q14332

- FZD2_HUMAN

UniProt

Q14332 - FZD2_HUMAN

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Protein

Frizzled-2

Gene

FZD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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.

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW
  2. PDZ domain binding Source: UniProtKB
  3. Wnt-activated receptor activity Source: RefGenome
  4. Wnt-protein binding Source: RefGenome

GO - Biological processi

  1. axonogenesis Source: RefGenome
  2. brain development Source: RefGenome
  3. canonical Wnt signaling pathway Source: UniProtKB
  4. cell-cell signaling Source: Ensembl
  5. cochlea morphogenesis Source: Ensembl
  6. epithelial cell differentiation Source: RefGenome
  7. gonad development Source: RefGenome
  8. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
  9. hard palate development Source: Ensembl
  10. inner ear receptor cell development Source: Ensembl
  11. membranous septum morphogenesis Source: Ensembl
  12. muscular septum morphogenesis Source: Ensembl
  13. neuron differentiation Source: UniProtKB
  14. outflow tract morphogenesis Source: Ensembl
  15. planar cell polarity pathway involved in neural tube closure Source: Ensembl
  16. positive regulation of cGMP metabolic process Source: BHF-UCL
  17. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  18. positive regulation of transcription, DNA-templated Source: BHF-UCL
  19. sensory perception of smell Source: Ensembl
  20. vasculature development Source: RefGenome
  21. Wnt signaling pathway, calcium modulating pathway Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_172631. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
REACT_172638. Asymmetric localization of PCP proteins.
REACT_172761. Ca2+ pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-2
Short name:
Fz-2
Short name:
hFz2
Alternative name(s):
FzE2
Gene namesi
Name:FZD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:4040. FZD2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 247224ExtracellularSequence AnalysisAdd
BLAST
Transmembranei248 – 26821Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini269 – 27911CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei280 – 30021Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini301 – 32727ExtracellularSequence AnalysisAdd
BLAST
Transmembranei328 – 34821Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini349 – 37022CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei371 – 39121Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini392 – 41423ExtracellularSequence AnalysisAdd
BLAST
Transmembranei415 – 43521Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini436 – 46126CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei462 – 48221Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini483 – 51937ExtracellularSequence AnalysisAdd
BLAST
Transmembranei520 – 54021Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini541 – 56525CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical part of cell Source: RefGenome
  2. clathrin-coated endocytic vesicle membrane Source: Reactome
  3. cytoplasm Source: BHF-UCL
  4. focal adhesion Source: UniProtKB
  5. integral component of membrane Source: UniProtKB-KW
  6. neuron projection membrane Source: RefGenome
  7. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28457.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 565542Frizzled-2PRO_0000012978Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi39 ↔ 100PROSITE-ProRule annotation
Disulfide bondi47 ↔ 93PROSITE-ProRule annotation
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi84 ↔ 121PROSITE-ProRule annotation
Disulfide bondi110 ↔ 150PROSITE-ProRule annotation
Disulfide bondi114 ↔ 138PROSITE-ProRule annotation
Glycosylationi154 – 1541N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ14332.
PaxDbiQ14332.
PRIDEiQ14332.

PTM databases

PhosphoSiteiQ14332.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiQ14332.
CleanExiHS_FZD2.
ExpressionAtlasiQ14332. baseline and differential.
GenevestigatoriQ14332.

Organism-specific databases

HPAiHPA057667.

Interactioni

Protein-protein interaction databases

BioGridi108811. 12 interactions.
IntActiQ14332. 1 interaction.
STRINGi9606.ENSP00000323901.

Structurei

3D structure databases

ProteinModelPortaliQ14332.
SMRiQ14332. Positions 39-145, 200-556.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 153120FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi543 – 5486Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi563 – 5653PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi181 – 1877Poly-Gly

Domaini

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

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOVERGENiHBG006977.
InParanoidiQ14332.
KOiK02235.
OMAiCENFPRH.
OrthoDBiEOG7M3J01.
PhylomeDBiQ14332.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q14332-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MRPRSALPRL LLPLLLLPAA GPAQFHGEKG ISIPDHGFCQ PISIPLCTDI
60 70 80 90 100
AYNQTIMPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF FLCSMYAPVC
110 120 130 140 150
TVLEQAIPPC RSICERARQG CEALMNKFGF QWPERLRCEH FPRHGAEQIC
160 170 180 190 200
VGQNHSEDGA PALLTTAPPP GLQPGAGGTP GGPGGGGAPP RYATLEHPFH
210 220 230 240 250
CPRVLKVPSY LSYKFLGERD CAAPCEPARP DGSMFFSQEE TRFARLWILT
260 270 280 290 300
WSVLCCASTF FTVTTYLVDM QRFRYPERPI IFLSGCYTMV SVAYIAGFVL
310 320 330 340 350
QERVVCNERF SEDGYRTVVQ GTKKEGCTIL FMMLYFFSMA SSIWWVILSL
360 370 380 390 400
TWFLAAGMKW GHEAIEANSQ YFHLAAWAVP AVKTITILAM GQIDGDLLSG
410 420 430 440 450
VCFVGLNSLD PLRGFVLAPL FVYLFIGTSF LLAGFVSLFR IRTIMKHDGT
460 470 480 490 500
KTEKLERLMV RIGVFSVLYT VPATIVIACY FYEQAFREHW ERSWVSQHCK
510 520 530 540 550
SLAIPCPAHY TPRMSPDFTV YMIKYLMTLI VGITSGFWIW SGKTLHSWRK
560
FYTRLTNSRH GETTV
Length:565
Mass (Da):63,554
Last modified:November 1, 1996 - v1
Checksum:iAA387876A1DDE063
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L37882 mRNA. Translation: AAB46397.1.
AB017364 mRNA. Translation: BAA34667.1.
BC113402 mRNA. Translation: AAI13403.1.
BC113404 mRNA. Translation: AAI13405.1.
CCDSiCCDS11484.1.
PIRiJE0338.
RefSeqiNP_001457.1. NM_001466.3.
UniGeneiHs.142912.
Hs.732654.

Genome annotation databases

EnsembliENST00000315323; ENSP00000323901; ENSG00000180340.
GeneIDi2535.
KEGGihsa:2535.
UCSCiuc002igx.2. human.

Polymorphism databases

DMDMi17433019.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L37882 mRNA. Translation: AAB46397.1 .
AB017364 mRNA. Translation: BAA34667.1 .
BC113402 mRNA. Translation: AAI13403.1 .
BC113404 mRNA. Translation: AAI13405.1 .
CCDSi CCDS11484.1.
PIRi JE0338.
RefSeqi NP_001457.1. NM_001466.3.
UniGenei Hs.142912.
Hs.732654.

3D structure databases

ProteinModelPortali Q14332.
SMRi Q14332. Positions 39-145, 200-556.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108811. 12 interactions.
IntActi Q14332. 1 interaction.
STRINGi 9606.ENSP00000323901.

Chemistry

GuidetoPHARMACOLOGYi 230.

Protein family/group databases

MEROPSi I93.001.
GPCRDBi Search...

PTM databases

PhosphoSitei Q14332.

Polymorphism databases

DMDMi 17433019.

Proteomic databases

MaxQBi Q14332.
PaxDbi Q14332.
PRIDEi Q14332.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000315323 ; ENSP00000323901 ; ENSG00000180340 .
GeneIDi 2535.
KEGGi hsa:2535.
UCSCi uc002igx.2. human.

Organism-specific databases

CTDi 2535.
GeneCardsi GC17P042645.
HGNCi HGNC:4040. FZD2.
HPAi HPA057667.
MIMi 600667. gene.
neXtProti NX_Q14332.
PharmGKBi PA28457.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG257258.
GeneTreei ENSGT00760000118864.
HOVERGENi HBG006977.
InParanoidi Q14332.
KOi K02235.
OMAi CENFPRH.
OrthoDBi EOG7M3J01.
PhylomeDBi Q14332.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_172631. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
REACT_172638. Asymmetric localization of PCP proteins.
REACT_172761. Ca2+ pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.

Miscellaneous databases

ChiTaRSi FZD2. human.
GeneWikii FZD2.
GenomeRNAii 2535.
NextBioi 10005.
PROi Q14332.
SOURCEi Search...

Gene expression databases

Bgeei Q14332.
CleanExi HS_FZD2.
ExpressionAtlasi Q14332. baseline and differential.
Genevestigatori Q14332.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiFZD2_HUMAN
AccessioniPrimary (citable) accession number: Q14332
Secondary accession number(s): Q0VG82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: November 26, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3