ID   FZD3_XENLA              Reviewed;         664 AA.
AC   O42579;
DT   05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 135.
DE   RecName: Full=Frizzled-3;
DE            Short=Fz-3;
DE            Short=Xfz3;
DE   Flags: Precursor;
GN   Name=fzd3; Synonyms=fz3;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Embryo;
RX   PubMed=9510023; DOI=10.1016/s0925-4773(97)00166-4;
RA   Shi D.-L., Goisset C., Boucaut J.-C.;
RT   "Expression of Xfz3, a Xenopus frizzled family member, is restricted to the
RT   early nervous system.";
RL   Mech. Dev. 70:35-47(1998).
RN   [2]
RP   MUTAGENESIS, DOMAIN K-T-X-X-X-W MOTIF, AND COUPLING TO BETA-CATENIN
RP   PATHWAY.
RX   PubMed=10990458; DOI=10.1093/emboj/19.18.4944;
RA   Umbhauer M., Djiane A., Goisset C., Penzo-Mendez A., Riou J.-F.,
RA   Boucaut J.-C., Shi D.-L.;
RT   "The C-terminal cytoplasmic Lys-Thr-X-X-X-Trp motif in frizzled receptors
RT   mediates Wnt/beta-catenin signalling.";
RL   EMBO J. 19:4944-4954(2000).
CC   -!- FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are
CC       coupled to the beta-catenin canonical signaling pathway, which leads to
CC       the activation of disheveled proteins, inhibition of GSK-3 kinase,
CC       nuclear accumulation of beta-catenin and activation of Wnt target
CC       genes. A second signaling pathway involving PKC and calcium fluxes has
CC       been seen for some family members, but it is not yet clear if it
CC       represents a distinct pathway or if it can be integrated in the
CC       canonical pathway, as PKC seems to be required for Wnt-mediated
CC       inactivation of GSK-3 kinase. Both pathways seem to involve
CC       interactions with G-proteins. Activated by Wnt8. Involved in
CC       transduction and intercellular transmission of polarity information
CC       during tissue morphogenesis and/or in differentiated tissues. Plays a
CC       role in controlling early axon growth and guidance processes necessary
CC       for the formation of a subset of central and peripheral major fiber
CC       tracts. Involved in the migration of cranial neural crest cells. May
CC       also be implicated in the transmission of sensory information from the
CC       trunk and limbs to the brain. Controls commissural sensory axons
CC       guidance after midline crossing along the anterior-posterior axis in
CC       the developing spinal cord in a Wnt-dependent signaling pathway.
CC       Together with FZD6, is involved in the neural tube closure and plays a
CC       role in the regulation of the establishment of planar cell polarity
CC       (PCP). Promotes neurogenesis by maintaining sympathetic neuroblasts
CC       within the cell cycle in a beta-catenin-dependent manner (By
CC       similarity). {ECO:0000250|UniProtKB:Q61086}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC       membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Cell
CC       surface {ECO:0000250|UniProtKB:Q61086}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:Q61086}; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expression restricted to the early nervous system.
CC   -!- DEVELOPMENTAL STAGE: Low expression from cleavage stages to the end of
CC       gastrulation; increases from neurulation onward. During neurulation,
CC       first localized to the anterior neural folds. As neurulation proceeds,
CC       the expression extends to the trunk neural fold, with low levels in the
CC       posterior neural fold. At the end of neurulation, strongly expressed as
CC       a large band in the midbrain. After neural tube closure, also detected
CC       in the optic lobes and otic vesicles. During the late development,
CC       expression remains restricted to the nervous system. Detected until at
CC       least the larval stages.
CC   -!- DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl
CC       (Disheveled) family members and is involved in the activation of the
CC       Wnt/beta-catenin signaling pathway. {ECO:0000269|PubMed:10990458}.
CC   -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC       {ECO:0000305}.
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DR   EMBL; AJ001754; CAA04977.1; -; mRNA.
DR   RefSeq; NP_001083918.1; NM_001090449.1.
DR   AlphaFoldDB; O42579; -.
DR   SMR; O42579; -.
DR   MINT; O42579; -.
DR   GlyCosmos; O42579; 2 sites, No reported glycans.
DR   GeneID; 399190; -.
DR   KEGG; xla:399190; -.
DR   AGR; Xenbase:XB-GENE-865070; -.
DR   CTD; 399190; -.
DR   Xenbase; XB-GENE-865070; fzd3.L.
DR   OrthoDB; 5483535at2759; -.
DR   Proteomes; UP000186698; Chromosome 5L.
DR   Bgee; 399190; Expressed in brain and 17 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR   GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR   GO; GO:0014036; P:neural crest cell fate specification; TAS:AgBase.
DR   GO; GO:0032880; P:regulation of protein localization; IDA:BHF-UCL.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd15033; 7tmF_FZD3; 1.
DR   CDD; cd07449; CRD_FZ3; 1.
DR   Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR015526; Frizzled/SFRP.
DR   InterPro; IPR000539; Frizzled/Smoothened_7TM.
DR   InterPro; IPR020067; Frizzled_dom.
DR   InterPro; IPR036790; Frizzled_dom_sf.
DR   InterPro; IPR041769; FZ3_CRD.
DR   InterPro; IPR017981; GPCR_2-like_7TM.
DR   PANTHER; PTHR11309; FRIZZLED; 1.
DR   PANTHER; PTHR11309:SF22; FRIZZLED-3; 1.
DR   Pfam; PF01534; Frizzled; 1.
DR   Pfam; PF01392; Fz; 1.
DR   PRINTS; PR00489; FRIZZLED.
DR   SMART; SM00063; FRI; 1.
DR   SMART; SM01330; Frizzled; 1.
DR   SUPFAM; SSF63501; Frizzled cysteine-rich domain; 1.
DR   PROSITE; PS50038; FZ; 1.
DR   PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Developmental protein; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Neurogenesis; Receptor;
KW   Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix;
KW   Wnt signaling pathway.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..664
FT                   /note="Frizzled-3"
FT                   /id="PRO_0000012984"
FT   TOPO_DOM        17..204
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        205..225
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        226..236
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        237..257
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        258..287
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        288..308
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        309..327
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        328..348
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        349..373
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        374..394
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        395..419
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        420..440
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        441..476
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        477..497
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        498..664
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          22..135
FT                   /note="FZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   REGION          537..664
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           501..506
FT                   /note="Lys-Thr-X-X-X-Trp motif, mediates interaction with
FT                   the PDZ domain of Dvl family members"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        544..585
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        586..600
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        608..628
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        629..664
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        41
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        27..88
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        35..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        72..109
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        98..132
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        102..126
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   MUTAGEN         501
FT                   /note="K->M: Complete loss of activity to induce the Wnt
FT                   target gene Siamois expression."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         502
FT                   /note="T->V: Complete loss of activity to induce the Wnt
FT                   target gene Siamois expression."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         503
FT                   /note="C->S: No effect."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         506
FT                   /note="W->G: Complete loss of activity to induce the Wnt
FT                   target gene Siamois expression."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         507
FT                   /note="A->V: No effect."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         508
FT                   /note="S->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:10990458"
FT   MUTAGEN         509
FT                   /note="F->L: No effect."
FT                   /evidence="ECO:0000269|PubMed:10990458"
SQ   SEQUENCE   664 AA;  75619 MW;  51BCC43BDA1791E5 CRC64;
     MAAYLISFIW VSVILAQKSM GHSLFACEPI TLRMCQDLPY NSTFMPNLLN HYDQQTAALA
     MEPFHPMVNL ECSRDLRPFL CALYTPVCME YGRMTLPCRK LCQRAYNECF KLMEMFGVPW
     PEEMECSRFP DCDEPYPRIV DISLSGEPSE ETPLAVQRDY GFWCPRELKI DPDLRSSFLG
     VRDCSPPCPH MYFRREELSF ARYFIGVISI VCLSATLFTF LTFLIDVTRF RYPERPIIFY
     AVCYMMVSLI FFIGFLLEDK VACNGANPSQ YKASTVTQGS HNKACTMLFM VLYFFTMAGS
     VWWVILTITW FLAAVPKWGS EAIEKKALLF HASAWGIPGT LTIILLAMNK IEGDNISGVC
     FVGLYDVHAL RYFVLAPLCL DVVVGVSLLL AGIISLNRVR IEIPLEKENQ DKLVKFMIRI
     GVFSILYLVP LLVVIGCYFY EQAYRGVWET TWVQERCREY HIPCPYKVTQ TSRPDLILFL
     MKYLMLLVVG IPSVFWVGSK KTCFEWASFF HGRKKKAGVN ESRQVLQEPD FAQSLLRDPN
     TPIVRKSRGT STQGTSTHAS STQLAMLDDQ RSKAGSVQSK VSSYHGSLHR SRDGRYTPCS
     YRGIEERLPH GSMSHLTDHS RHSSTHRLNE QSHQGSIRDL SNPLAHISHG TSMNRVIEAD
     ATSA
//