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Protein

Frizzled-2

Gene

FZD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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

  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: UniProtKB
  • Wnt-activated receptor activity Source: WormBase
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-4086398 Ca2+ pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
SIGNORiQ14332

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
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000180340.6
HGNCiHGNC:4040 FZD2
MIMi600667 gene
neXtProtiNX_Q14332

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 247ExtracellularSequence analysisAdd BLAST224
Transmembranei248 – 268Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini269 – 279CytoplasmicSequence analysisAdd BLAST11
Transmembranei280 – 300Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini301 – 327ExtracellularSequence analysisAdd BLAST27
Transmembranei328 – 348Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini349 – 370CytoplasmicSequence analysisAdd BLAST22
Transmembranei371 – 391Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini392 – 414ExtracellularSequence analysisAdd BLAST23
Transmembranei415 – 435Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini436 – 461CytoplasmicSequence analysisAdd BLAST26
Transmembranei462 – 482Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini483 – 519ExtracellularSequence analysisAdd BLAST37
Transmembranei520 – 540Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini541 – 565CytoplasmicSequence analysisAdd BLAST25

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2535
MalaCardsiFZD2
OpenTargetsiENSG00000180340
PharmGKBiPA28457

Chemistry databases

ChEMBLiCHEMBL3559686

Polymorphism and mutation databases

BioMutaiFZD2
DMDMi17433019

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001297824 – 565Frizzled-2Add BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 100PROSITE-ProRule annotation
Disulfide bondi47 ↔ 93PROSITE-ProRule annotation
Glycosylationi53N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi84 ↔ 121PROSITE-ProRule annotation
Disulfide bondi110 ↔ 150PROSITE-ProRule annotation
Disulfide bondi114 ↔ 138PROSITE-ProRule annotation
Glycosylationi154N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

EPDiQ14332
MaxQBiQ14332
PaxDbiQ14332
PeptideAtlasiQ14332
PRIDEiQ14332
ProteomicsDBi59968

PTM databases

iPTMnetiQ14332
PhosphoSitePlusiQ14332

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

BgeeiENSG00000180340
CleanExiHS_FZD2
GenevisibleiQ14332 HS

Organism-specific databases

HPAiHPA057667

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • Wnt-protein binding Source: GO_Central

Protein-protein interaction databases

BioGridi108811, 41 interactors
IntActiQ14332, 5 interactors
MINTiQ14332
STRINGi9606.ENSP00000323901

Structurei

3D structure databases

ProteinModelPortaliQ14332
SMRiQ14332
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 153FZPROSITE-ProRule annotationAdd BLAST120

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi543 – 548Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi563 – 565PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi181 – 187Poly-Gly7

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain 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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOVERGENiHBG006977
InParanoidiQ14332
KOiK02235
OMAiKDCAAPC
OrthoDBiEOG091G0N5M
PhylomeDBiQ14332
TreeFamiTF317907

Family and domain databases

Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR026550 FZD2
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF34 PTHR11309:SF34, 1 hit
PfamiView protein in Pfam
PF01534 Frizzled, 1 hit
PF01392 Fz, 1 hit
PRINTSiPR00489 FRIZZLED
SMARTiView protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit
SUPFAMiSSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

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.3 human

Similar proteinsi

Entry informationi

Entry nameiFZD2_HUMAN
AccessioniPrimary (citable) accession number: Q14332
Secondary accession number(s): Q0VG82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: July 18, 2018
This is version 169 of the entry and version 1 of the sequence. See 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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