FRIZ2_CAEEL
ID FRIZ2_CAEEL Reviewed; 578 AA.
AC G5ECQ2; Q9U8U6;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Frizzled-2 {ECO:0000312|WormBase:F27E11.3};
DE Flags: Precursor;
GN Name=cfz-2 {ECO:0000312|WormBase:F27E11.3};
GN ORFNames=F27E11.3 {ECO:0000312|WormBase:F27E11.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000312|EMBL:ABA18181.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kohara Y., Shin-i T., Suzuki Y., Sugano S., Thierry-Mieg D.,
RA Thierry-Mieg J.;
RT "The Caenorhabditis elegans transcriptome project, a complementary view of
RT the genome.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:BAA84678.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-534.
RX PubMed=10498678; DOI=10.1242/dev.126.20.4421;
RA Sato A., Kojima T., Ui-Tei K., Miyata Y., Saigo K.;
RT "Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of
RT Wingless signaling in wingless hypomorphic mutants.";
RL Development 126:4421-4430(1999).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16109397; DOI=10.1016/j.ydbio.2005.07.014;
RA Zinovyeva A.Y., Forrester W.C.;
RT "The C. elegans Frizzled CFZ-2 is required for cell migration and interacts
RT with multiple Wnt signaling pathways.";
RL Dev. Biol. 285:447-461(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19855022; DOI=10.1242/dev.038109;
RA Kennerdell J.R., Fetter R.D., Bargmann C.I.;
RT "Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance
RT and nerve ring placement in C. elegans.";
RL Development 136:3801-3810(2009).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20711352; DOI=10.1371/journal.pgen.1001056;
RA Song S., Zhang B., Sun H., Li X., Xiang Y., Liu Z., Huang X., Ding M.;
RT "A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis
RT elegans.";
RL PLoS Genet. 6:E1001056-E1001056(2010).
CC -!- FUNCTION: Receptor for Wnt proteins (PubMed:19855022, PubMed:20711352).
CC Most frizzled receptors are coupled to the beta-catenin canonical
CC signaling pathway, which leads to the activation of disheveled
CC proteins, inhibition of gsk-3 kinase, nuclear accumulation of beta-
CC catenin and activation of Wnt target genes. A second signaling pathway
CC involving PKC and calcium fluxes has been seen for some family members,
CC but it is not yet clear if it represents a distinct pathway or if it
CC can be integrated in the canonical pathway, as PKC seems to be required
CC for Wnt-mediated inactivation of gsk-3 kinase. Both pathways seem to
CC involve interactions with G-proteins (Probable). Required for the
CC migration and axon formation and guidance of different neuronal cell
CC types including canal-associated neurons (CAN), hermaphrodite-specific
CC neurons (HSN), anterior lateral microtubule neurons (ALM), and the
CC right Q neuroblast (QR) and its descendants (PubMed:16109397). Directs
CC ALM migration through frizzled protein mom-5 and Wnt ligands cwn-1,
CC cwn-2 and egl-20 (PubMed:16109397). May act redundantly with mom-5 to
CC direct CAN migration (PubMed:16109397). Plays a role in the
CC organization of head ganglion cells (PubMed:16109397). Probably by
CC acting as a receptor for Wnt ligand cwn-2, plays a role in the
CC positioning of the nerve ring and may in addition positively regulate
CC the neurite outgrowth of RME GABAergic motor neurons along the
CC anterior-posterior axis of the body (PubMed:19855022, PubMed:20711352).
CC {ECO:0000269|PubMed:16109397, ECO:0000269|PubMed:19855022,
CC ECO:0000269|PubMed:20711352, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in two pairs of head neurons and
CC throughout the pharynx. {ECO:0000269|PubMed:16109397}.
CC -!- DEVELOPMENTAL STAGE: First expressed at the 100-cell stage of
CC embryogenesis. During embryonic elongation, expressed in anterior,
CC posterior and midbody cells of the embryo and in cellular projections.
CC At hatching, expression is restricted to a few cells in the head and a
CC pair of cells in the tail. {ECO:0000269|PubMed:16109397}.
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:0000250|UniProtKB:Q9PUK8}.
CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
CC {ECO:0000250|UniProtKB:Q9VVX3}.
CC -!- DISRUPTION PHENOTYPE: Displaced anterior nerve ring and neuronal cell
CC migration defects including irregular localization of canal-associated
CC neurons (CAN), hermaphrodite-specific neurons (HSN), anterior lateral
CC microtubule neurons (ALM), and the right (but not the left) Q
CC neuroblast (QR) and its descendants (PubMed:16109397, PubMed:9851916).
CC Axon growth and guidance defects whereby some HSN, male CP neurons and
CC CAN extend ectopic axons or branches, and furthermore some HSN
CC irregularly route towards the ventral midline of the body
CC (PubMed:16109397). Disorganized cells of the anterior ganglion which
CC are normally compacted together when they form the head ganglion in
CC wild-type animals (PubMed:16109397). Double knockout with mom-5 or cwn-
CC 2 results in enhanced CAN migration defects (PubMed:16109397). Double
CC knockout with Wnt ligands cwn-1, cwn-2, egl-20 or frizzled protein mom-
CC 5 rescues the ALM migration defects in the single cfz-2 knockout
CC (PubMed:16109397). Triple knockout with cwn-1 and cwn-2 results in
CC enhanced neuronal cell migratory defects (PubMed:16109397).
CC {ECO:0000269|PubMed:16109397, ECO:0000269|PubMed:9851916}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA84678.1; Type=Erroneous gene model prediction; Evidence={ECO:0000303|PubMed:10498678};
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DR EMBL; DQ178242; ABA18181.1; -; mRNA.
DR EMBL; BX284605; CCD62501.1; -; Genomic_DNA.
DR EMBL; AB026113; BAA84678.1; ALT_SEQ; Genomic_DNA.
DR PIR; T37325; T37325.
DR RefSeq; NP_503965.2; NM_071564.5.
DR AlphaFoldDB; G5ECQ2; -.
DR SMR; G5ECQ2; -.
DR IntAct; G5ECQ2; 11.
DR STRING; 6239.F27E11.3a; -.
DR EPD; G5ECQ2; -.
DR PaxDb; G5ECQ2; -.
DR PeptideAtlas; G5ECQ2; -.
DR EnsemblMetazoa; F27E11.3.1; F27E11.3.1; WBGene00000478.
DR GeneID; 178768; -.
DR KEGG; cel:CELE_F27E11.3; -.
DR CTD; 178768; -.
DR WormBase; F27E11.3; CE39149; WBGene00000478; cfz-2.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000166857; -.
DR InParanoid; G5ECQ2; -.
DR OMA; MECYLLG; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; G5ECQ2; -.
DR Reactome; R-CEL-4086398; Ca2+ pathway.
DR Reactome; R-CEL-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-CEL-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-CEL-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR SignaLink; G5ECQ2; -.
DR PRO; PR:G5ECQ2; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000478; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0042813; F:Wnt receptor activity; IBA:GO_Central.
DR GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0097475; P:motor neuron migration; IGI:UniProtKB.
DR GO; GO:0097402; P:neuroblast migration; IGI:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IGI:UniProtKB.
DR GO; GO:1905485; P:positive regulation of motor neuron migration; IGI:UniProtKB.
DR GO; GO:1904937; P:sensory neuron migration; IGI:UniProtKB.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR000539; Frizzled/Smoothened_TM.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 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; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 2: Evidence at transcript 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..17
FT /evidence="ECO:0000255"
FT CHAIN 18..578
FT /note="Frizzled-2"
FT /evidence="ECO:0000305"
FT /id="PRO_5007661238"
FT TOPO_DOM 18..236
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 237..257
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..289
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..312
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 313..333
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..354
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 355..375
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..398
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 399..419
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..449
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 450..470
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..497
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 498..518
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 20..144
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 138..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 522..527
FT /note="Lys-Thr-X-X-X-Trp motif, mediates interaction with
FT the PDZ domain of Dvl family members"
FT /evidence="ECO:0000250|UniProtKB:Q8AVJ9"
FT MOTIF 556..558
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 25..86
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 33..79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 70..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 97..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 101..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 578 AA; 65025 MW; 3B2A3666A8DB3596 CRC64;
MLLRISVLFL LLGSCGALFG KRQKCEQITI PLCKGIGYNM TSFPNSYGHE KQEEAGLEVH
QFYPLVEVGC FQHLKFFLCT MYTPICQENY DKPILPCMEL CVEARSKCSP IMAKYGFRWP
ETLSCEALPK MSDQMSTGNI CAAPPDTPKK QHKGHHHKNQ NQNQNQNHNY SPDGPEVGIS
KIDNEVIAGP SECQCTCNQP FQFVASEKSK VGNVTNCAYS CHSPALAESH SLVSNWMAFW
SITCCVLASF TFLTFLIETD RFQYPERPIF MLAFCQLMVA VGFMIRYFVG HEEIACDSMR
IKGADDNSGS LCFVVFLLTY FFGMAASVWW VILSLTWVLS AASKWSPEAI SSFSFHFHVV
GWCLPAIQTV LVIVFNAIDG DPITGICYVG NTDLQFQRIF VLFPLLVYFI VGVLFLVIGF
CNLWSIRNEV QKQHPSLESA HKITQLMSKI GIFSLLYTIP SLLIICVLFY EQNHRSLWEQ
SQLCSCSPKQ TIGDSSLIIS LIKTCCMCIL GWTSGFWVCS TKTLSSWKNA ICCLGSSRSL
PKYQPADILY AKSDMSSSQF YNTSLRHNHL YGGIPDKL
