ID   LET23_CAEEL             Reviewed;        1323 AA.
AC   P24348;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   25-JUL-2006, sequence version 3.
DT   24-JAN-2024, entry version 212.
DE   RecName: Full=Receptor tyrosine-protein kinase let-23;
DE            EC=2.7.10.1;
DE   AltName: Full=Lethal protein 23;
DE   Flags: Precursor;
GN   Name=let-23 {ECO:0000312|WormBase:ZK1067.1a};
GN   Synonyms=kin-7 {ECO:0000312|WormBase:ZK1067.1a};
GN   ORFNames=ZK1067.1 {ECO:0000312|WormBase:ZK1067.1a};
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].
RX   PubMed=1979659; DOI=10.1038/348693a0;
RA   Aroian R.V., Koga M., Mendel J.E., Ohshima Y., Sternberg P.W.;
RT   "The let-23 gene necessary for Caenorhabditis elegans vulval induction
RT   encodes a tyrosine kinase of the EGF receptor subfamily.";
RL   Nature 348:693-699(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=8604137; DOI=10.1006/jmbi.1996.0107;
RA   Sakai T., Koga M., Ohshima Y.;
RT   "Genomic structure and 5' regulatory regions of the let-23 gene in the
RT   nematode C. elegans.";
RL   J. Mol. Biol. 256:548-555(1996).
RN   [3]
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   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-368.
RX   PubMed=2071015; DOI=10.1093/genetics/128.2.251;
RA   Aroian R.V., Sternberg P.W.;
RT   "Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine
RT   kinase gene required for vulval induction.";
RL   Genetics 128:251-267(1991).
RN   [5]
RP   FUNCTION, AND MUTAGENESIS OF CYS-368; GLY-469; CYS-700; CYS-753; THR-1065
RP   AND GLY-1074.
RX   PubMed=8313880; DOI=10.1002/j.1460-2075.1994.tb06269.x;
RA   Aroian R.V., Les G.M., Sternberg P.W.;
RT   "Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define
RT   elements important for cell-type specificity and function.";
RL   EMBO J. 13:360-366(1994).
RN   [6]
RP   FUNCTION, AND MUTAGENESIS OF THR-1065.
RX   PubMed=9491893; DOI=10.1016/s0092-8674(00)80945-9;
RA   Clandinin T.R., DeModena J.A., Sternberg P.W.;
RT   "Inositol trisphosphate mediates a RAS-independent response to LET-23
RT   receptor tyrosine kinase activation in C. elegans.";
RL   Cell 92:523-533(1998).
RN   [7]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=Bristol N2;
RX   PubMed=10359617; DOI=10.1091/mbc.10.6.2087;
RA   Whitfield C.W., Benard C., Barnes T., Hekimi S., Kim S.K.;
RT   "Basolateral localization of the Caenorhabditis elegans epidermal growth
RT   factor receptor in epithelial cells by the PDZ protein lin-10.";
RL   Mol. Biol. Cell 10:2087-2100(1999).
RN   [8]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-368.
RX   PubMed=15194811; DOI=10.1091/mbc.e04-03-0198;
RA   Yin X., Gower N.J., Baylis H.A., Strange K.;
RT   "Inositol 1,4,5-trisphosphate signaling regulates rhythmic contractile
RT   activity of myoepithelial sheath cells in Caenorhabditis elegans.";
RL   Mol. Biol. Cell 15:3938-3949(2004).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-376, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Bristol N2;
RX   PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA   Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA   Taoka M., Takahashi N., Isobe T.;
RT   "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT   elegans and suggests an atypical translocation mechanism for integral
RT   membrane proteins.";
RL   Mol. Cell. Proteomics 6:2100-2109(2007).
RN   [10]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17891142; DOI=10.1038/nn1981;
RA   Van Buskirk C., Sternberg P.W.;
RT   "Epidermal growth factor signaling induces behavioral quiescence in
RT   Caenorhabditis elegans.";
RL   Nat. Neurosci. 10:1300-1307(2007).
RN   [11]
RP   FUNCTION, AND MUTAGENESIS OF CYS-364.
RX   PubMed=20230814; DOI=10.1016/j.ydbio.2010.03.004;
RA   Simms C.L., Baillie D.L.;
RT   "A strawberry notch homolog, let-765/nsh-1, positively regulates lin-3/egf
RT   expression to promote RAS-dependent vulval induction in C. elegans.";
RL   Dev. Biol. 341:472-485(2010).
RN   [12]
RP   MUTAGENESIS OF CYS-364 AND 1318-GLN--LEU-1323.
RX   PubMed=27207389; DOI=10.1016/j.ydbio.2016.05.009;
RA   Flibotte S., Kim B.R., Van de Laar E., Brown L., Moghal N.;
RT   "The SWI/SNF chromatin remodeling complex exerts both negative and positive
RT   control over LET-23/EGFR-dependent vulval induction in Caenorhabditis
RT   elegans.";
RL   Dev. Biol. 415:46-63(2016).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP   1318-GLN--LEU-1323.
RX   PubMed=32053105; DOI=10.7554/elife.50986;
RA   Haag A., Walser M., Henggeler A., Hajnal A.;
RT   "The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling
RT   in C. elegans and in human cells.";
RL   Elife 9:0-0(2020).
CC   -!- FUNCTION: Tyrosine-protein kinase receptor which, upon binding ligand
CC       lin-3, activates 2 signaling cascades: the let-60/Ras and MAP kinase
CC       signaling pathway and the let-60-independent phospholipase C-mediated
CC       Ca(2+) signaling pathway. Each pathway regulates distinct functions. By
CC       activating let-60/Ras, regulates larval development, induction of vulva
CC       cell precursors during vulva development, male spicule formation and
CC       posterior development of the epidermis (PubMed:2071015, PubMed:8313880,
CC       PubMed:9491893, PubMed:20230814, PubMed:32053105). Probably by
CC       activating phospholipase plc-3 and inositol 1,4,5-trisphosphate
CC       receptor itr-1 signaling cascade downstream of ligand lin-3, plays a
CC       role in ovulation by promoting ovulatory gonadal sheath cell
CC       contractions (PubMed:9491893, PubMed:15194811). Probably by regulating
CC       neuronal transmission in ALA neurons, mediates, independently of let-
CC       60/Ras, the decrease in pharyngeal pumping and locomotion during the
CC       quiescent state that precedes each larval molt, downstream of lin-3 and
CC       upstream of plc-3 (PubMed:17891142). {ECO:0000269|PubMed:15194811,
CC       ECO:0000269|PubMed:17891142, ECO:0000269|PubMed:20230814,
CC       ECO:0000269|PubMed:2071015, ECO:0000269|PubMed:32053105,
CC       ECO:0000269|PubMed:8313880, ECO:0000269|PubMed:9491893}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:10359617, ECO:0000269|PubMed:32053105}; Single-pass
CC       type I membrane protein {ECO:0000269|PubMed:10359617}. Basolateral cell
CC       membrane {ECO:0000269|PubMed:10359617, ECO:0000269|PubMed:32053105};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:10359617}.
CC       Note=Basolateral and apical membrane of cell junctions in epithelial
CC       vulval precursor cells. {ECO:0000269|PubMed:10359617}.
CC   -!- TISSUE SPECIFICITY: Expressed in vulval precursor cells (at protein
CC       level) (PubMed:10359617). Expressed in ALA neurons, 2 ventral head
CC       neurons, a single neuron in the tail, pharyngeal-intestinal valve and
CC       posterior arcade epithelial cells (PubMed:17891142).
CC       {ECO:0000269|PubMed:10359617, ECO:0000269|PubMed:17891142}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during L2 and L3 larval stages
CC       (PubMed:10359617). Highly expressed in vulval precursor cells P6.p in
CC       late L2 and early L3 stage larvae (PubMed:32053105).
CC       {ECO:0000269|PubMed:10359617, ECO:0000269|PubMed:32053105}.
CC   -!- DISRUPTION PHENOTYPE: Larval lethality, lack of vulva formation,
CC       infertility and lack of male spicule formation (PubMed:2071015). RNAi-
CC       mediated knockdown causes sterility, a small decrease in the peak rate
CC       of sheath cell contractions and a delay in the onset of ovulatory
CC       contractions (PubMed:15194811). Restores normal pharyngeal pumping rate
CC       in 30 percent of animals overexpressing lin-3 (PubMed:17891142).
CC       {ECO:0000269|PubMed:15194811, ECO:0000269|PubMed:17891142,
CC       ECO:0000269|PubMed:2071015}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA09729.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X57767; CAA40919.1; -; mRNA.
DR   EMBL; D63426; BAA09729.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BX284602; CAA93882.3; -; Genomic_DNA.
DR   PIR; E88257; E88257.
DR   PIR; S70712; S70712.
DR   RefSeq; NP_495962.2; NM_063561.4.
DR   PDB; 5WNO; X-ray; 2.39 A; A=866-1191.
DR   PDBsum; 5WNO; -.
DR   AlphaFoldDB; P24348; -.
DR   SMR; P24348; -.
DR   BioGRID; 39787; 108.
DR   DIP; DIP-1014N; -.
DR   IntAct; P24348; 2.
DR   MINT; P24348; -.
DR   STRING; 6239.ZK1067.1d.1; -.
DR   GlyCosmos; P24348; 8 sites, No reported glycans.
DR   iPTMnet; P24348; -.
DR   PaxDb; 6239-ZK1067-1c; -.
DR   EnsemblMetazoa; ZK1067.1a.1; ZK1067.1a.1; WBGene00002299.
DR   GeneID; 174462; -.
DR   UCSC; ZK1067.1; c. elegans.
DR   AGR; WB:WBGene00002299; -.
DR   WormBase; ZK1067.1a; CE03840; WBGene00002299; let-23.
DR   eggNOG; KOG1025; Eukaryota.
DR   GeneTree; ENSGT00940000168382; -.
DR   InParanoid; P24348; -.
DR   PhylomeDB; P24348; -.
DR   BRENDA; 2.7.10.1; 1045.
DR   Reactome; R-CEL-1227986; Signaling by ERBB2.
DR   Reactome; R-CEL-1250196; SHC1 events in ERBB2 signaling.
DR   Reactome; R-CEL-1251985; Nuclear signaling by ERBB4.
DR   Reactome; R-CEL-1253288; Downregulation of ERBB4 signaling.
DR   Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-CEL-177929; Signaling by EGFR.
DR   Reactome; R-CEL-179812; GRB2 events in EGFR signaling.
DR   Reactome; R-CEL-180292; GAB1 signalosome.
DR   Reactome; R-CEL-180336; SHC1 events in EGFR signaling.
DR   Reactome; R-CEL-182971; EGFR downregulation.
DR   Reactome; R-CEL-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-CEL-212718; EGFR interacts with phospholipase C-gamma.
DR   Reactome; R-CEL-2179392; EGFR Transactivation by Gastrin.
DR   Reactome; R-CEL-416572; Sema4D induced cell migration and growth-cone collapse.
DR   Reactome; R-CEL-445144; Signal transduction by L1.
DR   Reactome; R-CEL-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-CEL-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-CEL-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-CEL-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-CEL-8863795; Downregulation of ERBB2 signaling.
DR   Reactome; R-CEL-9009391; Extra-nuclear estrogen signaling.
DR   Reactome; R-CEL-9652282; Drug-mediated inhibition of ERBB2 signaling.
DR   SignaLink; P24348; -.
DR   PRO; PR:P24348; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00002299; Expressed in larva and 3 other cell types or tissues.
DR   ExpressionAtlas; P24348; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR   GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:WormBase.
DR   GO; GO:0005911; C:cell-cell junction; IDA:WormBase.
DR   GO; GO:0016328; C:lateral plasma membrane; IDA:WormBase.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005006; F:epidermal growth factor receptor activity; IDA:WormBase.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:WormBase.
DR   GO; GO:0030539; P:male genitalia development; IMP:WormBase.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR   GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR   GO; GO:0030728; P:ovulation; IMP:WormBase.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR   GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0040026; P:positive regulation of vulval development; IMP:WormBase.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:0030431; P:sleep; IMP:WormBase.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   GO; GO:0060065; P:uterus development; IMP:UniProtKB.
DR   GO; GO:0072327; P:vulval cell fate specification; IMP:UniProtKB.
DR   CDD; cd00064; FU; 5.
DR   Gene3D; 3.80.20.20; Receptor L-domain; 2.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR   InterPro; IPR006212; Furin_repeat.
DR   InterPro; IPR032778; GF_recep_IV.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR000494; Rcpt_L-dom.
DR   InterPro; IPR036941; Rcpt_L-dom_sf.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   PANTHER; PTHR24416:SF566; EPIDERMAL GROWTH FACTOR RECEPTOR; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   Pfam; PF00757; Furin-like; 1.
DR   Pfam; PF14843; GF_recep_IV; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF01030; Recep_L_domain; 2.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00261; FU; 7.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 3.
DR   SUPFAM; SSF52058; L domain-like; 2.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell membrane; Developmental protein;
KW   Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW   Phosphoprotein; Receptor; Reference proteome; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..1323
FT                   /note="Receptor tyrosine-protein kinase let-23"
FT                   /id="PRO_0000016677"
FT   TOPO_DOM        21..818
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        819..839
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        840..1323
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          885..1152
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1265..1323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1265..1292
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1010
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         891..899
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         919
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   CARBOHYD        91
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        255
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        376
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17761667"
FT   CARBOHYD        561
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        655
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        746
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        776
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        220..228
FT                   /evidence="ECO:0000250"
FT   DISULFID        224..236
FT                   /evidence="ECO:0000250"
FT   DISULFID        244..251
FT                   /evidence="ECO:0000250"
FT   DISULFID        248..262
FT                   /evidence="ECO:0000250"
FT   DISULFID        263..271
FT                   /evidence="ECO:0000250"
FT   DISULFID        267..279
FT                   /evidence="ECO:0000250"
FT   DISULFID        282..291
FT                   /evidence="ECO:0000250"
FT   DISULFID        295..322
FT                   /evidence="ECO:0000250"
FT   DISULFID        326..337
FT                   /evidence="ECO:0000250"
FT   DISULFID        341..356
FT                   /evidence="ECO:0000250"
FT   DISULFID        359..364
FT                   /evidence="ECO:0000250"
FT   DISULFID        520..529
FT                   /evidence="ECO:0000250"
FT   DISULFID        524..537
FT                   /evidence="ECO:0000250"
FT   DISULFID        540..549
FT                   /evidence="ECO:0000250"
FT   DISULFID        553..567
FT                   /evidence="ECO:0000250"
FT   DISULFID        570..577
FT                   /evidence="ECO:0000250"
FT   DISULFID        574..585
FT                   /evidence="ECO:0000250"
FT   DISULFID        588..604
FT                   /evidence="ECO:0000250"
FT   DISULFID        608..620
FT                   /evidence="ECO:0000250"
FT   DISULFID        623..632
FT                   /evidence="ECO:0000250"
FT   DISULFID        627..644
FT                   /evidence="ECO:0000250"
FT   DISULFID        647..660
FT                   /evidence="ECO:0000255"
FT   DISULFID        670..693
FT                   /evidence="ECO:0000255"
FT   DISULFID        696..703
FT                   /evidence="ECO:0000255"
FT   DISULFID        700..715
FT                   /evidence="ECO:0000255"
FT   DISULFID        717..731
FT                   /evidence="ECO:0000255"
FT   DISULFID        735..750
FT                   /evidence="ECO:0000255"
FT   DISULFID        753..763
FT                   /evidence="ECO:0000255"
FT   DISULFID        757..771
FT                   /evidence="ECO:0000255"
FT   DISULFID        774..787
FT                   /evidence="ECO:0000255"
FT   DISULFID        791..805
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         364
FT                   /note="C->Y: In sa62; multivulva phenotype. RNAi-mediated
FT                   knockdown of let-765 suppresses the multivulva phenotype.
FT                   Multivulva phenotype enhanced in a swsn-4 (sy598) mutant
FT                   background."
FT                   /evidence="ECO:0000269|PubMed:20230814,
FT                   ECO:0000269|PubMed:27207389"
FT   MUTAGEN         368
FT                   /note="C->Y: In sy10; severe larval lethality, lack of
FT                   vulva induction, infertile and lack of male spicule
FT                   formation. Impaired ovulation characterized by a delay in
FT                   the initiation of ovulatory sheath cell contractions and
FT                   prolonged ovulatory contractions."
FT                   /evidence="ECO:0000269|PubMed:15194811,
FT                   ECO:0000269|PubMed:2071015, ECO:0000269|PubMed:8313880"
FT   MUTAGEN         469
FT                   /note="G->R: In mn216; larval lethality."
FT                   /evidence="ECO:0000269|PubMed:8313880"
FT   MUTAGEN         700
FT                   /note="C->W: In mn23; larval lethality."
FT                   /evidence="ECO:0000269|PubMed:8313880"
FT   MUTAGEN         753
FT                   /note="C->Y: In SY11."
FT                   /evidence="ECO:0000269|PubMed:8313880"
FT   MUTAGEN         1065
FT                   /note="T->I: In sy16; larval lethality and lack of vulva
FT                   induction. Viability, vulva induction but not fertility are
FT                   restored in a let-60 (n1046gf) mutant background. Viability
FT                   is not restored in a lfe-1 (sy290) or lfe-2 (sy326) mutant
FT                   background. Fertility is restored in a let-60 (n1046gf) and
FT                   lfe-1 (sy290) mutant background."
FT                   /evidence="ECO:0000269|PubMed:8313880,
FT                   ECO:0000269|PubMed:9491893"
FT   MUTAGEN         1074
FT                   /note="G->E: In SY7."
FT                   /evidence="ECO:0000269|PubMed:8313880"
FT   MUTAGEN         1318..1323
FT                   /note="Missing: In sy1; reduces vulval induction. The
FT                   vulval induction incidence is further reduced in a chp-1
FT                   tm2277 mutant background and in swsn-4 (os13) and swsn-1
FT                   (os22) mutant backgrounds."
FT                   /evidence="ECO:0000269|PubMed:27207389,
FT                   ECO:0000269|PubMed:32053105"
FT   CONFLICT        1179
FT                   /note="D -> H (in Ref. 1; CAA40919)"
FT                   /evidence="ECO:0000305"
FT   HELIX           880..882
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          883..892
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          898..904
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          914..921
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           929..939
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          949..954
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          959..964
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           971..977
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   TURN            978..981
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           984..1003
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1013..1015
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          1016..1020
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   STRAND          1023..1026
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   TURN            1032..1034
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1049..1053
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1056..1060
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1066..1081
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   TURN            1087..1090
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1095..1101
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1114..1122
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   TURN            1128..1130
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1134..1144
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1148..1150
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1160..1177
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   TURN            1178..1180
FT                   /evidence="ECO:0007829|PDB:5WNO"
FT   HELIX           1184..1189
FT                   /evidence="ECO:0007829|PDB:5WNO"
SQ   SEQUENCE   1323 AA;  150511 MW;  6B0307EE53EEFA99 CRC64;
     MRYPPSIGSI LLIIPIFLTF FGNSNAQLWK RCVSPQDCLC SGTTNGISRY GTGNILEDLE
     TMYRGCRRVY GNLEITWIEA NEIKKWREST NSTVDPKNED SPLKSINFFD NLEEIRGSLI
     IYRANIQKIS FPRLRVIYGD EVFHDNALYI HKNDKVHEVV MRELRVIRNG SVTIQDNPKM
     CYIGDKIDWK ELLYDPDVQK VETTNSHQHC YQNGKSMAKC HESCNDKCWG SGDNDCQRVY
     RSVCPKSCSQ CFYSNSTSSY ECCDSACLGG CTGHGPKNCI ACSKYELDGI CIETCPSRKI
     FNHKTGRLVF NPDGRYQNGN HCVKECPPEL LIENDVCVRH CSDGHHYDAT KDVRECEKCR
     SSSCPKICTV DGHLTNETLK NLEGCEQIDG HLIIEHAFTY EQLKVLETVK IVSEYITIVQ
     QNFYDLKFLK NLQIIEGRKL HNVRWALAIY QCDDLEELSL NSLKLIKTGA VLIMKNHRLC
     YVSKIDWSSI ITSKGKDNKP SLAIAENRDS KLCETEQRVC DKNCNKRGCW GKEPEDCLEC
     KTWKSVGTCV EKCDTKGFLR NQTSMKCERC SPECETCNGL GELDCLTCRH KTLYNSDFGN
     RMECVHDCPV SHFPTQKNVC EKCHPTCYDN GCTGPDSNLG YGGCKQCKYA VKYENDTIFC
     LQSSGMNNVC VENDLPNYYI STYDTEGVIE THCEKCSISC KTCSSAGRNV VQNKCVCKHV
     EYQPNPSERI CMDQCPVNSF MVPDTNNTVC KKCHHECDQN YHCANGQSTG CQKCKNFTVF
     KGDIAQCVSE CPKNLPFSNP ANGECLDYDI ASRQRKTRMV IIGSVLFGFA VMFLFILLVY
     WRCQRIGKKL KIAEMVDMPE LTPIDASVRP NMSRICLIPS SELQTKLDKK LGAGAFGTVF
     AGIYYPKRAK NVKIPVAIKV FQTDQSQTDE MLEEATNMFR LRHDNLLKII GFCMHDDGLK
     IVTIYRPLGN LQNFLKLHKE NLGAREQVLY CYQIASGMQY LEKQRVVHRD LATRNVLVKK
     FNHVEITDFG LSKILKHDAD SITIKSGKVA IKWLAIEIFS KHCYTHASDV WAFGVTCWEI
     ITFGQSPYQG MSTDSIHNFL KDGNRLSQPP NCSQDLYQEL LRCWMADPKS RPGFEILYER
     FKEFCKVPQL FLENSNKISE SDLSAEERFQ TERIREMFDG NIDPQMYFDQ GSLPSMPSSP
     TSMATFTIPH GDLMNRMQSV NSSRYKTEPF DYGSTAQEDN SYLIPKTKEV QQSAVLYTAV
     TNEDGQTELS PSNGDYYNQP NTPSSSSGYY NEPHLKTKKP ETSEEAEAVQ YENEEVSQKE
     TCL
//