LAG2_CAEEL
ID LAG2_CAEEL Reviewed; 402 AA.
AC P45442;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Protein lag-2;
DE AltName: Full=Lethal protein 461;
DE Flags: Precursor;
GN Name=lag-2 {ECO:0000312|WormBase:Y73C8B.4};
GN Synonyms=let-461 {ECO:0000312|WormBase:Y73C8B.4};
GN ORFNames=Y73C8B.4 {ECO:0000312|WormBase:Y73C8B.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 [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF GLY-262.
RC STRAIN=Bristol N2;
RX PubMed=8139658; DOI=10.1038/368150a0;
RA Tax F.E., Yeargers J.J., Thomas J.H.;
RT "Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with
RT Delta and Serrate of Drosophila.";
RL Nature 368:150-154(1994).
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, TISSUE SPECIFICITY, AND MUTAGENESIS OF 79-GLN--VAL-402.
RX PubMed=7607081; DOI=10.1242/dev.120.10.2913;
RA Henderson S.T., Gao D., Lambie E.J., Kimble J.;
RT "lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of
RT C. elegans.";
RL Development 120:2913-2924(1994).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF 281-VAL--VAL-402.
RX PubMed=8575327; DOI=10.1242/dev.121.12.4275;
RA Fitzgerald K., Greenwald I.;
RT "Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic
RT signalling activity of their extracellular domains in vivo.";
RL Development 121:4275-4282(1995).
RN [5]
RP DOMAIN, AND MUTAGENESIS OF 287-SER--VAL-402 AND 308-LYS--VAL-402.
RX PubMed=9307971; DOI=10.1091/mbc.8.9.1751;
RA Henderson S.T., Gao D., Christensen S., Kimble J.;
RT "Functional domains of LAG-2, a putative signaling ligand for LIN-12 and
RT GLP-1 receptors in Caenorhabditis elegans.";
RL Mol. Biol. Cell 8:1751-1762(1997).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=14960273; DOI=10.1016/s1534-5807(04)00021-8;
RA Chen N., Greenwald I.;
RT "The lateral signal for LIN-12/Notch in C. elegans vulval development
RT comprises redundant secreted and transmembrane DSL proteins.";
RL Dev. Cell 6:183-192(2004).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18599512; DOI=10.1242/dev.012435;
RA Ouellet J., Li S., Roy R.;
RT "Notch signalling is required for both dauer maintenance and recovery in C.
RT elegans.";
RL Development 135:2583-2592(2008).
RN [8]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18036582; DOI=10.1016/j.ydbio.2007.10.027;
RA Foehr M.L., Liu J.;
RT "Dorsoventral patterning of the C. elegans postembryonic mesoderm requires
RT both LIN-12/Notch and TGFbeta signaling.";
RL Dev. Biol. 313:256-266(2008).
RN [9]
RP FUNCTION, AND INTERACTION WITH LIN-12.
RX PubMed=18700817; DOI=10.1371/journal.pbio.0060196;
RA Komatsu H., Chao M.Y., Larkins-Ford J., Corkins M.E., Somers G.A.,
RA Tucey T., Dionne H.M., White J.Q., Wani K., Boxem M., Hart A.C.;
RT "OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans
RT vulval development.";
RL PLoS Biol. 6:e196-e196(2008).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19502484; DOI=10.1242/dev.034603;
RA Nadarajan S., Govindan J.A., McGovern M., Hubbard E.J., Greenstein D.;
RT "MSP and GLP-1/Notch signaling coordinately regulate actomyosin-dependent
RT cytoplasmic streaming and oocyte growth in C. elegans.";
RL Development 136:2223-2234(2009).
RN [11]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=21737278; DOI=10.1016/j.cub.2011.06.016;
RA Bertrand V., Bisso P., Poole R.J., Hobert O.;
RT "Notch-dependent induction of left/right asymmetry in C. elegans
RT interneurons and motoneurons.";
RL Curr. Biol. 21:1225-1231(2011).
RN [12]
RP DEVELOPMENTAL STAGE.
RX PubMed=21596897; DOI=10.1534/genetics.111.128389;
RA Zhang X., Greenwald I.;
RT "Spatial regulation of lag-2 transcription during vulval precursor cell
RT fate patterning in Caenorhabditis elegans.";
RL Genetics 188:847-858(2011).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27661254; DOI=10.7554/elife.17218;
RA McClatchey S.T., Wang Z., Linden L.M., Hastie E.L., Wang L., Shen W.,
RA Chen A., Chi Q., Sherwood D.R.;
RT "Boundary cells restrict dystroglycan trafficking to control basement
RT membrane sliding during tissue remodeling.";
RL Elife 5:0-0(2016).
RN [14]
RP FUNCTION.
RX PubMed=29523076; DOI=10.1186/s12868-018-0408-1;
RA Bennett H.L., Khoruzhik Y., Hayden D., Huang H., Sanders J., Walsh M.B.,
RA Biron D., Hart A.C.;
RT "Normal sleep bouts are not essential for C. elegans survival and FoxO is
RT important for compensatory changes in sleep.";
RL BMC Neurosci. 19:10-10(2018).
CC -!- FUNCTION: Probable ligand for lin-12/Notch and glp-1/Notch receptors
CC and involved in the mediation of Notch signaling (PubMed:8139658,
CC PubMed:7607081, PubMed:18036582, PubMed:18700817, PubMed:8575327).
CC Involved in the lin-12/Notch pathway signaling of cell fate in vulval
CC precursor cells (VPCs) and in the postembryonic mesodermal lineage (M
CC lineage), acting redundantly with dsl-1 and apx-1 (PubMed:14960273,
CC PubMed:18036582). Functions in uterine cells to promote basement
CC membrane mobility during tissue remodeling (PubMed:27661254,
CC PubMed:8139658). Required for oocyte growth control, acting redundantly
CC with apx-1, perhaps signaling via the glp-1/Notch pathway
CC (PubMed:19502484). Plays a role in Notch-dependent induction of left-
CC right asymmetry in interneurons and motoneurons (PubMed:21737278).
CC Involved in maintaining the developmentally arrested larval state known
CC as dauer, probably signaling in the glp-1/Notch pathway
CC (PubMed:18599512). Required for normal sleep bout quantity and arousal
CC thresholds during the transition from the last larval stage to
CC adulthood in well-fed animals (PubMed:29523076).
CC {ECO:0000269|PubMed:14960273, ECO:0000269|PubMed:18036582,
CC ECO:0000269|PubMed:18599512, ECO:0000269|PubMed:18700817,
CC ECO:0000269|PubMed:19502484, ECO:0000269|PubMed:21737278,
CC ECO:0000269|PubMed:27661254, ECO:0000269|PubMed:29523076,
CC ECO:0000269|PubMed:7607081, ECO:0000269|PubMed:8139658,
CC ECO:0000269|PubMed:8575327}.
CC -!- SUBUNIT: May interact with lin-12 / Notch receptor.
CC {ECO:0000269|PubMed:18700817}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:7607081,
CC ECO:0000305|PubMed:8139658}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the gonad distal tip cell (DTC) of
CC hermaphrodites. {ECO:0000269|PubMed:7607081}.
CC -!- DEVELOPMENTAL STAGE: Expressed in cells immediately adjacent to ventral
CC mesodermal lineage (M lineage) cells, but not next to dorsal M lineage
CC cells, beginning at the 4-M stage (PubMed:18036582). Expressed in all
CC six vulval precursor cells (VPCs) in the early larval L3 stage,
CC subsequently more highly expressed in P6.p while the expression in the
CC other VPCs diminishes (PubMed:14960273, PubMed:21596897). Expressed in
CC the anchor cell (AC) and distal tip cells (DTCs) of the somatic gonad
CC at larval stage L3 (PubMed:21596897). Expressed in the inter labial IL2
CC neurons at the onset of and throughout the developmentally arrested
CC larval state known as dauer (PubMed:18599512).
CC {ECO:0000269|PubMed:14960273, ECO:0000269|PubMed:18036582,
CC ECO:0000269|PubMed:18599512, ECO:0000269|PubMed:21596897}.
CC -!- DOMAIN: The N-terminal region and DSL domain may be involved in
CC interacting with Notch receptors. {ECO:0000303|PubMed:8139658,
CC ECO:0000303|PubMed:9307971}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in cells of the pi
CC uterine cell lineage results in impaired basement membrane mobility
CC (PubMed:27661254). RNAi-mediated knockdown, on a lin-15 mutant
CC background, causes adjacent vulval precursor cells (VPCs) to adopt
CC altered cell fate (PubMed:14960273). RNAi-mediated knockdown, when
CC combined with knockdown of apx-1, on a dsl-1 mutant background, causes
CC adjacent vulval precursor cells (VPCs) to adopt altered cell fate;
CC phenotype exacerbated on double mutant lin-15;dsl-1 background
CC (PubMed:14960273). RNAi-mediated knockdown, on a lin-12 mutant
CC background, induces the presence of 1-2 extra mesodermal lineage (M
CC lineage)-derived coelomocytes and the concomitant loss of sex myoblasts
CC on the ventral side of the animal (PubMed:18036582). On an apx-1 mutant
CC background, RNAi-mediated knockdown causes germ cells to display
CC nuclear morphology consistent with meiotic prophase or gametogenesis in
CC adult hermaphrodites (PubMed:19502484). {ECO:0000269|PubMed:14960273,
CC ECO:0000269|PubMed:18036582, ECO:0000269|PubMed:19502484,
CC ECO:0000269|PubMed:27661254}.
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DR EMBL; X77495; CAA54629.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD66873.1; -; Genomic_DNA.
DR PIR; S42367; S42367.
DR RefSeq; NP_503877.1; NM_071476.1.
DR AlphaFoldDB; P45442; -.
DR BioGRID; 43812; 3.
DR DIP; DIP-46051N; -.
DR IntAct; P45442; 1.
DR STRING; 6239.Y73C8B.4; -.
DR PaxDb; P45442; -.
DR EnsemblMetazoa; Y73C8B.4.1; Y73C8B.4.1; WBGene00002246.
DR GeneID; 178755; -.
DR KEGG; cel:CELE_Y73C8B.4; -.
DR UCSC; Y73C8B.4; c. elegans.
DR CTD; 178755; -.
DR WormBase; Y73C8B.4; CE22970; WBGene00002246; lag-2.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00970000195885; -.
DR HOGENOM; CLU_693062_0_0_1; -.
DR InParanoid; P45442; -.
DR OMA; MGRLRCD; -.
DR OrthoDB; 1103092at2759; -.
DR PhylomeDB; P45442; -.
DR SignaLink; P45442; -.
DR PRO; PR:P45442; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00002246; Expressed in embryo and 3 other tissues.
DR GO; GO:0031253; C:cell projection membrane; IDA:WormBase.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:WormBase.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:WormBase.
DR GO; GO:0005112; F:Notch binding; IPI:WormBase.
DR GO; GO:0001708; P:cell fate specification; IMP:WormBase.
DR GO; GO:0008406; P:gonad development; IMP:WormBase.
DR GO; GO:0043055; P:maintenance of dauer; IGI:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:WormBase.
DR GO; GO:0110011; P:regulation of basement membrane organization; IMP:UniProtKB.
DR GO; GO:1905936; P:regulation of germ cell proliferation; IMP:UniProtKB.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IMP:UniProtKB.
DR GO; GO:0040028; P:regulation of vulval development; IMP:WormBase.
DR GO; GO:0030431; P:sleep; IMP:UniProtKB.
DR InterPro; IPR001774; DSL.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR039178; Lag2.
DR PANTHER; PTHR22669; PTHR22669; 1.
DR Pfam; PF01414; DSL; 1.
DR Pfam; PF00008; EGF; 1.
DR SMART; SM00051; DSL; 1.
DR SMART; SM00181; EGF; 2.
DR PROSITE; PS51051; DSL; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Differentiation; Disulfide bond;
KW EGF-like domain; Glycoprotein; Membrane; Notch signaling pathway;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..402
FT /note="Protein lag-2"
FT /id="PRO_0000007632"
FT TOPO_DOM 16..279
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 280..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 122..166
FT /note="DSL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00377"
FT DOMAIN 171..216
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 229..266
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 124..133
FT /evidence="ECO:0000250"
FT DISULFID 137..149
FT /evidence="ECO:0000250"
FT DISULFID 157..166
FT /evidence="ECO:0000250"
FT DISULFID 175..183
FT /evidence="ECO:0000250"
FT DISULFID 177..204
FT /evidence="ECO:0000250"
FT DISULFID 206..215
FT /evidence="ECO:0000250"
FT DISULFID 233..245
FT /evidence="ECO:0000250"
FT DISULFID 239..254
FT /evidence="ECO:0000250"
FT DISULFID 256..265
FT /evidence="ECO:0000250"
FT MUTAGEN 79..402
FT /note="Missing: In q411; causes death of first stage L1
FT larvae with various cell fate transformations."
FT /evidence="ECO:0000269|PubMed:7607081"
FT MUTAGEN 262
FT /note="G->D: In sa37; suppresses lin-12 function."
FT /evidence="ECO:0000269|PubMed:8139658"
FT MUTAGEN 281..402
FT /note="Missing: Causes abnormal proximal proliferation in
FT the germline and formation of ectopic vulvae."
FT /evidence="ECO:0000269|PubMed:8575327"
FT MUTAGEN 287..402
FT /note="Missing: Causes abnormal proximal proliferation in
FT the germline and formation of ectopic vulvae. Also,
FT expression pattern of glp-1 is abnormal, being found in
FT both distal and proximal regions of the germline. On a lag-
FT 2(q411) mutant background, causes death soon after
FT hatching."
FT /evidence="ECO:0000269|PubMed:9307971"
FT MUTAGEN 308..402
FT /note="Missing: Causes formation of ectopic vulvae. On a
FT lag-2(q411) mutant background, suppresses abnormal
FT phenotype."
FT /evidence="ECO:0000269|PubMed:9307971"
SQ SEQUENCE 402 AA; 44603 MW; 076A99DA0288A123 CRC64;
MIAYFLLLLT CLPVLQARVE VHQEFISSKR VSVRFEIVTE SHSPNRPVTF DLFPRGPKTN
IILLDTFNPV FNFSIQLVQP FTGQPLGDRI YRKVQFSGTN QPWINDTFTT TSGISLSVAT
EVTCARNYFG NRCENFCDAH LAKAARKRCD AMGRLRCDIG WMGPHCGQAV DPRKCSCEND
GICVSSMIHP SQPNQTSSNE QLICECTNGF TGTRCEIFGF NQFQLTAPRP DACSVKDACL
NGAKCFPNGP KVFCSCAVGF IGEFCEISLT TTTPTTVEIT VSTSGYSSAV YITVALFVIF
SIIIGCFKYK FKPMRQQALA RGQVPEPYKM PETKSMLIDP EASEAQKKVF TIEGSVQKID
EEVRYTSAPR KYESNNEYAV IQKSTPPPPS LSPPSIPACH YV
