WNT2_CAEEL
ID WNT2_CAEEL Reviewed; 360 AA.
AC P34889;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Protein Wnt-2;
DE Flags: Precursor;
GN Name=cwn-2 {ECO:0000312|WormBase:W01B6.1};
GN Synonyms=wnt-2 {ECO:0000312|WormBase:W01B6.1};
GN ORFNames=W01B6.1 {ECO:0000312|WormBase:W01B6.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=8510930;
RA Shackleford G.M., Shivakumar S., Shiue L., Mason J., Kenyon C.,
RA Varmus H.E.;
RT "Two wnt genes in Caenorhabditis elegans.";
RL Oncogene 8:1857-1864(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 [3]
RP FUNCTION, AND DISRUPTION 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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16516839; DOI=10.1016/j.devcel.2006.02.010;
RA Pan C.L., Howell J.E., Clark S.G., Hilliard M., Cordes S., Bargmann C.I.,
RA Garriga G.;
RT "Multiple Wnts and frizzled receptors regulate anteriorly directed cell and
RT growth cone migrations in Caenorhabditis elegans.";
RL Dev. Cell 10:367-377(2006).
RN [5]
RP FUNCTION.
RX PubMed=18622031; DOI=10.1534/genetics.108.090290;
RA Zinovyeva A.Y., Yamamoto Y., Sawa H., Forrester W.C.;
RT "Complex network of Wnt signaling regulates neuronal migrations during
RT Caenorhabditis elegans development.";
RL Genetics 179:1357-1371(2008).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP 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 [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19561603; DOI=10.1038/nn.2347;
RA Hayashi Y., Hirotsu T., Iwata R., Kage-Nakadai E., Kunitomo H.,
RA Ishihara T., Iino Y., Kubo T.;
RT "A trophic role for Wnt-Ror kinase signaling during developmental pruning
RT in Caenorhabditis elegans.";
RL Nat. Neurosci. 12:981-987(2009).
RN [8]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF CYS-138.
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).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22022276; DOI=10.1371/journal.pgen.1002308;
RA Yamamoto Y., Takeshita H., Sawa H.;
RT "Multiple Wnts redundantly control polarity orientation in Caenorhabditis
RT elegans epithelial stem cells.";
RL PLoS Genet. 7:E1002308-E1002308(2011).
RN [10]
RP FUNCTION.
RX PubMed=25917219; DOI=10.1016/j.ydbio.2015.04.015;
RA Chien S.C., Gurling M., Kim C., Craft T., Forrester W., Garriga G.;
RT "Autonomous and nonautonomous regulation of Wnt-mediated neuronal polarity
RT by the C. elegans Ror kinase CAM-1.";
RL Dev. Biol. 404:55-65(2015).
CC -!- FUNCTION: Ligand for members of the frizzled family of seven
CC transmembrane receptors. Probable developmental protein. May be a
CC signaling molecule which affects the development of discrete regions of
CC tissues. Is likely to signal over only few cell diameters. Involved in
CC the correct positioning of the developing nerve ring and in axon
CC guidance of SIA and SIB neurons, probably by binding to tyrosine kinase
CC receptor cam-1 (PubMed:19855022). In addition, regulates the
CC positioning of some head neuronal cells, muscle arms associated with
CC the nerve ring and the excretory pore (PubMed:19855022). Together with
CC Wnt ligand cwn-1, regulates the migration of CAN, ALM, BDU and HSN
CC neurons during embryogenesis, the migration of QL and QR neuroblast
CC descendants during larval development, and polarity of ALM neurons
CC (PubMed:16109397, PubMed:16516839, PubMed:18622031, PubMed:25917219).
CC May act through the wnt receptor cfz-2 to regulate QR neuroblast
CC descendant migration, and to direct ALM migration (PubMed:16109397).
CC Also plays a role in axon growth and guidance in HSN and male CP
CC neurons (PubMed:16109397). In addition, together with wnt ligand cwn-1,
CC negatively regulates developmental neurite pruning of AIM neurons
CC probably by acting as a ligand for receptor tyrosine kinase cam-1
CC (PubMed:19561603). Through the cam-1 receptor also probably regulates
CC the outgrowth of neurites from RME GABAergic motor neurons
CC (PubMed:20711352). May act redundantly with other Wnt ligands such as
CC cwn-1 and mom-2 to control seam cell polarity (PubMed:22022276).
CC {ECO:0000269|PubMed:16109397, ECO:0000269|PubMed:16516839,
CC ECO:0000269|PubMed:18622031, ECO:0000269|PubMed:19561603,
CC ECO:0000269|PubMed:19855022, ECO:0000269|PubMed:20711352,
CC ECO:0000269|PubMed:22022276, ECO:0000269|PubMed:25917219, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:Q2LMP1}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine, pharynx, anterior body wall
CC muscle, vulva, some pharyngeal neurons and SMD head neurons
CC (PubMed:19855022, PubMed:19561603, PubMed:22022276). Expressed along
CC the boundary between the intestine and muscle or hypodermis, but is
CC also expressed in the hypodermis in cells including seam cells
CC (PubMed:22022276). {ECO:0000269|PubMed:19561603,
CC ECO:0000269|PubMed:19855022, ECO:0000269|PubMed:22022276}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the comma stage in pharyngeal muscles
CC and the developing intestine (PubMed:19855022). Detected in all larval
CC forms and adults, but is most abundant in the embryonic stage
CC (PubMed:8510930). At the two-fold stage of embryogenesis, mainly it is
CC expressed in the intestine (PubMed:20711352). During late
CC embryogenesis, before hatching, it is expressed in the posterior
CC pharyngeal bulb and the pharyngeal-intestine (PubMed:20711352). After
CC the L1 stage of larval development it is expressed in the anterior part
CC of the animal in tissues including the pharynx, body wall muscle and
CC ventral cord neurons (PubMed:20711352). {ECO:0000269|PubMed:19855022,
CC ECO:0000269|PubMed:20711352, ECO:0000269|PubMed:8510930}.
CC -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC receptors. Depalmitoleoylation leads to Wnt signaling pathway
CC inhibition. {ECO:0000250|UniProtKB:P27467,
CC ECO:0000250|UniProtKB:P56704}.
CC -!- DISRUPTION PHENOTYPE: Anterior displacement of the nerve ring in L1
CC stage mutant animals (PubMed:19855022). Defective ALM, BDU, CAN and QR
CC neuroblast migration and irregular CP and CAN axon growth and guidance
CC (PubMed:16109397). Double knockout with cfz-2 results in enhanced CAN
CC migration defects, but the same QR neuroblast migration defects as the
CC single cfz-2 knockout alone (PubMed:16109397). Double knockout with
CC cwn-1 results in ALM, CAN and HSN migration defects (PubMed:16109397,
CC PubMed:16516839). Triple knockout with cwn-1 and cfz-2 results in
CC enhanced neuronal cell migratory defects (PubMed:16109397).
CC {ECO:0000269|PubMed:16109397, ECO:0000269|PubMed:16516839,
CC ECO:0000269|PubMed:19855022}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; X72943; CAA51448.1; -; mRNA.
DR EMBL; Z68301; CAA92624.1; -; Genomic_DNA.
DR PIR; S32695; S32695.
DR PIR; T26037; T26037.
DR RefSeq; NP_501822.1; NM_069421.4.
DR AlphaFoldDB; P34889; -.
DR SMR; P34889; -.
DR BioGRID; 42973; 3.
DR STRING; 6239.W01B6.1; -.
DR EPD; P34889; -.
DR PaxDb; P34889; -.
DR EnsemblMetazoa; W01B6.1.1; W01B6.1.1; WBGene00000858.
DR GeneID; 177870; -.
DR KEGG; cel:CELE_W01B6.1; -.
DR UCSC; W01B6.1; c. elegans.
DR CTD; 177870; -.
DR WormBase; W01B6.1; CE03753; WBGene00000858; cwn-2.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000169151; -.
DR HOGENOM; CLU_033039_0_1_1; -.
DR InParanoid; P34889; -.
DR OMA; EHARMLM; -.
DR OrthoDB; 695671at2759; -.
DR PhylomeDB; P34889; -.
DR Reactome; R-CEL-3238698; WNT ligand biogenesis and trafficking.
DR Reactome; R-CEL-4086398; Ca2+ pathway.
DR Reactome; R-CEL-4086400; PCP/CE pathway.
DR Reactome; R-CEL-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-CEL-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-CEL-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR SignaLink; P34889; -.
DR PRO; PR:P34889; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000858; Expressed in pharyngeal muscle cell (C elegans) and 8 other tissues.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005109; F:frizzled binding; ISS:WormBase.
DR GO; GO:0048018; F:receptor ligand activity; ISS:WormBase.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:WormBase.
DR GO; GO:0033564; P:anterior/posterior axon guidance; IMP:WormBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0060573; P:cell fate specification involved in pattern specification; IGI:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:1904936; P:interneuron migration; IMP:UniProtKB.
DR GO; GO:0097475; P:motor neuron migration; IMP:UniProtKB.
DR GO; GO:0097402; P:neuroblast migration; IMP:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; IMP: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 GO; GO:0010084; P:specification of animal organ axis polarity; IGI:WormBase.
DR GO; GO:0040025; P:vulval development; IGI:WormBase.
DR GO; GO:0016055; P:Wnt signaling pathway; IGI:WormBase.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01349; WNTPROTEIN.
DR SMART; SM00097; WNT1; 1.
DR PROSITE; PS00246; WNT1; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Lipoprotein; Neurogenesis; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..360
FT /note="Protein Wnt-2"
FT /id="PRO_0000041474"
FT LIPID 219
FT /note="O-palmitoleoyl serine; by mom-1"
FT /evidence="ECO:0000250|UniProtKB:P56704"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 80..91
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 130..138
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 140..158
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 213..227
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 215..222
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 289..320
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 305..315
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 319..359
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 335..350
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 337..347
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 342..343
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT MUTAGEN 138
FT /note="C->Y: In xd1; loss of neurite growth from RMED and
FT RMEV GABAergic motor neurons."
FT /evidence="ECO:0000269|PubMed:20711352"
FT CONFLICT 73
FT /note="A -> R (in Ref. 1; CAA51448)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="H -> D (in Ref. 1; CAA51448)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="A -> R (in Ref. 1; CAA51448)"
FT /evidence="ECO:0000305"
FT CONFLICT 229..230
FT /note="MQ -> IE (in Ref. 1; CAA51448)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="S -> A (in Ref. 1; CAA51448)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 40436 MW; EC5471B865355F72 CRC64;
MIPRRSCWLI LLLNLLNVQS LLDASWWSTV AQLSTALAGH NVKPVCELPG LSPGQAQVCE
LFKDHMPAVS IGAQNAIQEC QRQFTGHRWN CSTHYSTGML GPIHKMATRE AAFTYAILSA
GVTHEIGRRC KQGLLTSCGC SDETKPKNVP TDWSWGGCGD NVEYGYKFSR DFIDIREKEH
DPKRNHDNGR SLMNRRNNEA GRKILKRHRK PKCKCHGVSG ACNMKTCWMQ LPSMEQVGKI
LRNKYDKAIR VQINDRGNLQ LLADEATKER KTRALPTDLV FMDDSPDYCR FDRHSGTLGT
EGRVCKRGSG GAEGCDSLCC GRGYNTYTQE VKSKCNCKFE WCCKVVCQTC NNVTQVDICK
