LIN3_CAEEL
ID LIN3_CAEEL Reviewed; 438 AA.
AC Q03345; G5ECQ0; G5ECS1; G5EFX0;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Protein lin-3;
DE AltName: Full=Abnormal cell lineage protein 3;
DE AltName: Full=Lethal protein 94;
DE Flags: Precursor;
GN Name=lin-3; Synonyms=let-94; ORFNames=F36H1.4;
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] (ISOFORMS A AND C), AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=1641037; DOI=10.1038/358470a0;
RA Hill R.J., Sternberg P.W.;
RT "The gene lin-3 encodes an inductive signal for vulval development in C.
RT elegans.";
RL Nature 358:470-476(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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.
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 [4]
RP FUNCTION.
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 [5]
RP FUNCTION (ISOFORMS A AND C), AND ALTERNATIVE SPLICING.
RX PubMed=15455032; DOI=10.1371/journal.pbio.0020334;
RA Dutt A., Canevascini S., Froehli-Hoier E., Hajnal A.;
RT "EGF signal propagation during C. elegans vulval development mediated by
RT ROM-1 rhomboid.";
RL PLoS Biol. 2:E334-E334(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16678779; DOI=10.1016/j.devcel.2006.04.001;
RA Cui M., Chen J., Myers T.R., Hwang B.J., Sternberg P.W., Greenwald I.,
RA Han M.;
RT "SynMuv genes redundantly inhibit lin-3/EGF expression to prevent
RT inappropriate vulval induction in C. elegans.";
RL Dev. Cell 10:667-672(2006).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
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).
CC -!- FUNCTION: Probable ligand for tyrosine kinase receptor let-23.
CC Essential for vulval induction, where it acts downstream of the
CC synthetic multivulva (synMuv) class genes (PubMed:1641037,
CC PubMed:15455032, PubMed:16678779, PubMed:17891142). Probably by
CC activating let-23, phospholipase plc-3 and inositol 1,4,5-trisphosphate
CC receptor itr-1 signaling cascade, plays a role in ovulation by
CC promoting gonadal sheath cell contractions and spermatheca dilatation
CC during ovulation (PubMed:15194811, PubMed:9491893). Probably by
CC regulating neuronal transmission in ALA neurons, mediates the decrease
CC in pharyngeal pumping and locomotion during the quiescent state that
CC precedes each larval molt, by activating receptor lin-23-mediated
CC signaling cascade (PubMed:17891142). {ECO:0000269|PubMed:15194811,
CC ECO:0000269|PubMed:15455032, ECO:0000269|PubMed:1641037,
CC ECO:0000269|PubMed:16678779, ECO:0000269|PubMed:17891142,
CC ECO:0000269|PubMed:9491893}.
CC -!- FUNCTION: [Isoform a]: Essential for vulval induction; its activity on
CC vulval precursor cells is partially dependent on rom-1.
CC {ECO:0000269|PubMed:15455032}.
CC -!- FUNCTION: [Isoform c]: Essential for vulval induction; acts
CC independently of rom-1. {ECO:0000269|PubMed:15455032}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=a {ECO:0000312|WormBase:F36H1.4a}; Synonyms=lin-3L
CC {ECO:0000303|PubMed:15455032};
CC IsoId=Q03345-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F36H1.4b};
CC IsoId=Q03345-2; Sequence=VSP_001396;
CC Name=c {ECO:0000312|WormBase:F36H1.4c}; Synonyms=lin-3S
CC {ECO:0000303|PubMed:15455032};
CC IsoId=Q03345-3; Sequence=VSP_001397;
CC Name=d {ECO:0000312|WormBase:F36H1.4d}; Synonyms=lin-3XL
CC {ECO:0000303|PubMed:15455032};
CC IsoId=Q03345-4; Sequence=VSP_001396, VSP_053622;
CC Name=e {ECO:0000312|WormBase:F36H1.4e};
CC IsoId=Q03345-5; Sequence=VSP_053623;
CC Name=f {ECO:0000312|WormBase:F36H1.4f};
CC IsoId=Q03345-6; Sequence=VSP_001396, VSP_053624;
CC -!- DEVELOPMENTAL STAGE: Expressed at all larval stages.
CC {ECO:0000269|PubMed:17891142}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in combination with
CC double mutants for the class A and B synMuv genes lin-36;lin-15A, lin-
CC 8;lin-15B, lin-15AB, lin-35;lin-8, lin-8;lin-36, lin-8;lin-9, lin-
CC 8;lin-37 or dpl-1;lin-15A results in suppression of the synthetic
CC multivulva phenotype. {ECO:0000269|PubMed:16678779}.
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DR EMBL; X68070; CAA48207.1; -; mRNA.
DR EMBL; BX284604; CAA92997.2; -; Genomic_DNA.
DR EMBL; AL032641; CAA92997.2; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAD27623.1; -; Genomic_DNA.
DR EMBL; AL032641; CAD27623.1; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAD30434.1; -; Genomic_DNA.
DR EMBL; AL032641; CAD30434.1; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAL44969.1; -; Genomic_DNA.
DR EMBL; AL032641; CAL44969.1; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAP03133.1; -; Genomic_DNA.
DR EMBL; AL032641; CAP03133.1; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAQ35042.1; -; Genomic_DNA.
DR EMBL; AL032641; CAQ35042.1; JOINED; Genomic_DNA.
DR PIR; D88826; D88826.
DR PIR; S28263; S28263.
DR RefSeq; NP_001076688.1; NM_001083219.2.
DR RefSeq; NP_001122777.1; NM_001129305.1. [Q03345-5]
DR RefSeq; NP_001122778.1; NM_001129306.2.
DR RefSeq; NP_741488.1; NM_171418.5. [Q03345-1]
DR RefSeq; NP_741489.1; NM_171918.5. [Q03345-3]
DR RefSeq; NP_741490.1; NM_171919.4. [Q03345-2]
DR AlphaFoldDB; Q03345; -.
DR BioGRID; 43101; 11.
DR STRING; 6239.F36H1.4f.1; -.
DR PeptideAtlas; Q03345; -.
DR PRIDE; Q03345; -.
DR EnsemblMetazoa; F36H1.4a.1; F36H1.4a.1; WBGene00002992. [Q03345-1]
DR EnsemblMetazoa; F36H1.4b.1; F36H1.4b.1; WBGene00002992. [Q03345-2]
DR EnsemblMetazoa; F36H1.4b.2; F36H1.4b.2; WBGene00002992. [Q03345-2]
DR EnsemblMetazoa; F36H1.4b.3; F36H1.4b.3; WBGene00002992. [Q03345-2]
DR EnsemblMetazoa; F36H1.4c.1; F36H1.4c.1; WBGene00002992. [Q03345-3]
DR EnsemblMetazoa; F36H1.4d.1; F36H1.4d.1; WBGene00002992. [Q03345-4]
DR EnsemblMetazoa; F36H1.4e.1; F36H1.4e.1; WBGene00002992. [Q03345-5]
DR EnsemblMetazoa; F36H1.4f.1; F36H1.4f.1; WBGene00002992. [Q03345-6]
DR GeneID; 178001; -.
DR KEGG; cel:CELE_F36H1.4; -.
DR UCSC; F36H1.4a; c. elegans. [Q03345-1]
DR CTD; 178001; -.
DR WormBase; F36H1.4a; CE28021; WBGene00002992; lin-3. [Q03345-1]
DR WormBase; F36H1.4b; CE18670; WBGene00002992; lin-3. [Q03345-2]
DR WormBase; F36H1.4c; CE30348; WBGene00002992; lin-3. [Q03345-3]
DR WormBase; F36H1.4d; CE40413; WBGene00002992; lin-3. [Q03345-4]
DR WormBase; F36H1.4e; CE41535; WBGene00002992; lin-3. [Q03345-5]
DR WormBase; F36H1.4f; CE42534; WBGene00002992; lin-3. [Q03345-6]
DR eggNOG; ENOG502TH25; Eukaryota.
DR InParanoid; Q03345; -.
DR OMA; AINYSGH; -.
DR OrthoDB; 969485at2759; -.
DR SignaLink; Q03345; -.
DR PRO; PR:Q03345; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002992; Expressed in reproductive system and 8 other tissues.
DR ExpressionAtlas; Q03345; baseline and differential.
DR GO; GO:0005615; C:extracellular space; ISS:WormBase.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0008083; F:growth factor activity; NAS:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:WormBase.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:WormBase.
DR GO; GO:0031129; P:inductive cell-cell signaling; IMP:WormBase.
DR GO; GO:0030539; P:male genitalia development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0018991; P:oviposition; IMP:WormBase.
DR GO; GO:0030728; P:ovulation; IMP:WormBase.
DR GO; GO:0060279; P:positive regulation of ovulation; IMP:UniProtKB.
DR GO; GO:0040026; P:positive regulation of vulval development; IMP:WormBase.
DR GO; GO:0009791; P:post-embryonic development; IMP:WormBase.
DR GO; GO:0042659; P:regulation of cell fate specification; IMP:WormBase.
DR GO; GO:0030431; P:sleep; IMP:WormBase.
DR GO; GO:0040025; P:vulval development; IMP:UniProtKB.
DR InterPro; IPR000742; EGF-like_dom.
DR SMART; SM00181; EGF; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Disulfide bond; EGF-like domain; Glycoprotein;
KW Growth factor; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..13
FT /evidence="ECO:0000255"
FT CHAIN 14..438
FT /note="Protein lin-3"
FT /id="PRO_0000007633"
FT TOPO_DOM 14..230
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 150..194
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 35..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..82
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 154..164
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 158..182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 184..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..20
FT /note="MRKMLLFCILLLFMPQFTVS -> MFGKSIPERLLVAF (in isoform
FT e)"
FT /evidence="ECO:0000305"
FT /id="VSP_053623"
FT VAR_SEQ 19..20
FT /note="Missing (in isoform b, isoform d and isoform f)"
FT /evidence="ECO:0000305"
FT /id="VSP_001396"
FT VAR_SEQ 211..225
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000303|PubMed:1641037"
FT /id="VSP_001397"
FT VAR_SEQ 211..225
FT /note="VRLSTMSSTAQLLVQ -> GKTKKPLIFMVHHPNQTISTTPSSQDSEISSIF
FT SGLYERIV (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_053622"
FT VAR_SEQ 225
FT /note="Q -> QGKTKKPLIFMVHHPNQTISTTPSSQDSEISSIFSGLYERIV (in
FT isoform f)"
FT /evidence="ECO:0000305"
FT /id="VSP_053624"
SQ SEQUENCE 438 AA; 48924 MW; 3434C779D85B4501 CRC64;
MRKMLLFCIL LLFMPQFTVS ESCLPSWFRQ ERSAPEQLQS AENAAENSGS VPPDTSRNSL
ETNEIGDAPS STSTPETPTE TTISEAGDDE KRTEEVAKEL IEKEAEYEGE YEDEKVDEEV
EEALKYNEDA TQDATSTLKP AVRKEIEKLK EAKCKDYCHH NATCHVEVIF REDRVSAVVP
SCHCPQGWEG TRCDRHYVQA FYAPINGRYN VRLSTMSSTA QLLVQQSSTS AIPAFAFLIV
MLIMFITIVV YAYRRMSKRS DDMTYTMSHM CPPEAFNVLK TPNGRHIPVH QIPSCSYTIP
TPGTVPPNIS STPGSRIPTR QQAIRNNEQA RNNFFSILRS QGTIPSRSIN DDDTPKHYKS
VPRVEVSAIN YSGHIDFSTV SYQSTESEVS KASVTCPPPA HTVINIELDS ADTNFRSPSR
SSGEQGSPAT CEPMIRHT
