LAG3_CAEEL
ID LAG3_CAEEL Reviewed; 490 AA.
AC Q09260; Q9NGS2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein lag-3;
DE AltName: Full=Abnormal cell lineage protein 3;
DE AltName: Full=Abnormal germline proliferation protein 3;
GN Name=sel-8; Synonyms=lag-3; ORFNames=C32A3.1;
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] (ISOFORMS A AND B), AND FUNCTION.
RX PubMed=10830967; DOI=10.1038/35012645;
RA Petcherski A.G., Kimble J.;
RT "LAG-3 is a putative transcriptional activator in the C. elegans Notch
RT pathway.";
RL Nature 405:364-368(2000).
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, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 409-GLN--ASN-490.
RX PubMed=10884418; DOI=10.1073/pnas.97.14.7877;
RA Doyle T.G., Wen C., Greenwald I.;
RT "SEL-8, a nuclear protein required for LIN-12 and GLP-1 signaling in
RT Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7877-7881(2000).
RN [4]
RP FUNCTION.
RX PubMed=16319922; DOI=10.1038/sj.emboj.7600901;
RA Lee M.H., Hook B., Lamont L.B., Wickens M., Kimble J.;
RT "LIP-1 phosphatase controls the extent of germline proliferation in
RT Caenorhabditis elegans.";
RL EMBO J. 25:88-96(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17317671; DOI=10.1074/jbc.m608974200;
RA Zhao Y., Katzman R.B., Delmolino L.M., Bhat I., Zhang Y., Gurumurthy C.B.,
RA Germaniuk-Kurowska A., Reddi H.V., Solomon A., Zeng M.S., Kung A., Ma H.,
RA Gao Q., Dimri G., Stanculescu A., Miele L., Wu L., Griffin J.D.,
RA Wazer D.E., Band H., Band V.;
RT "The notch regulator MAML1 interacts with p53 and functions as a
RT coactivator.";
RL J. Biol. Chem. 282:11969-11981(2007).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=33033228; DOI=10.1073/pnas.2013163117;
RA Robinson-Thiewes S., McCloskey J., Kimble J.;
RT "Two classes of active transcription sites and their roles in developmental
RT regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:26812-26821(2020).
RN [7] {ECO:0007744|PDB:2FO1}
RP X-RAY CRYSTALLOGRAPHY (3.12 ANGSTROMS) OF 52-114 IN COMPLEX WITH LIN-12;
RP LAG-1 AND DNA, AND FUNCTION.
RX PubMed=16530045; DOI=10.1016/j.cell.2006.01.035;
RA Wilson J.J., Kovall R.A.;
RT "Crystal structure of the CSL-Notch-Mastermind ternary complex bound to
RT DNA.";
RL Cell 124:985-996(2006).
CC -!- FUNCTION: glp-1/Notch and lin-12/Notch proteins promote signaling by
CC recruiting lag-3 to target promoters, where it functions as a
CC transcriptional activator, probably as part of a complex with a Notch
CC intracellular domain (NICD) and the transcription regulator lag-1
CC (PubMed:10830967, PubMed:10884418, PubMed:16530045). Involved in the
CC p53-mediated germ-cell apoptotic response to DNA damage, perhaps acting
CC as a transcriptional activator (PubMed:17317671). May regulate
CC phosphatase lip-1 mRNA transcription downstream of glp-1
CC (PubMed:16319922). {ECO:0000269|PubMed:10830967,
CC ECO:0000269|PubMed:10884418, ECO:0000269|PubMed:16319922,
CC ECO:0000269|PubMed:16530045, ECO:0000269|PubMed:17317671}.
CC -!- SUBUNIT: Component of a complex consisting of at least a lin-12/Notch
CC intracellular domain (NICD), lag-1, and lag-3 (PubMed:10830967,
CC PubMed:16530045). Interacts with a NICD of lin-12/Notch or glp-1/Notch;
CC the interactions are direct (PubMed:10830967, PubMed:16530045).
CC {ECO:0000269|PubMed:10830967, ECO:0000269|PubMed:16530045}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10884418}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q09260-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q09260-2; Sequence=VSP_003908;
CC -!- TISSUE SPECIFICITY: Expressed in the progenitor zone and the early
CC pachytene region of the hermaphrodite gonad.
CC {ECO:0000269|PubMed:33033228}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes multiple defects,
CC including large vulval protrusions in hermaphrodites, premature
CC differentiation of germ cells as sperm, and embryonic arrest around the
CC onset of morphogenesis (PubMed:10884418). RNAi-mediated knockdown
CC causes a partial decrease in apoptosis in germ line cells, in the F1
CC generation, induced by gamma-irradiation (PubMed:17317671). RNAi-
CC mediated knockdown, during treatment by gamma-irradiation, reduces the
CC expression of the p53 target genes, ced-13 and egl-1 (PubMed:17317671).
CC {ECO:0000269|PubMed:10884418, ECO:0000269|PubMed:17317671}.
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; AF241847; AAF71523.1; -; mRNA.
DR EMBL; AF241846; AAF71522.1; -; mRNA.
DR EMBL; Z48241; CAA88284.1; -; Genomic_DNA.
DR EMBL; Z48241; CAC42265.1; -; Genomic_DNA.
DR PIR; T19628; T19628.
DR RefSeq; NP_001021194.1; NM_001026023.2.
DR RefSeq; NP_001021195.1; NM_001026024.2. [Q09260-2]
DR PDB; 2FO1; X-ray; 3.12 A; D=52-114.
DR PDBsum; 2FO1; -.
DR AlphaFoldDB; Q09260; -.
DR SMR; Q09260; -.
DR BioGRID; 40704; 16.
DR ComplexPortal; CPX-3152; CSL-Notch-Mastermind transcription factor complex.
DR IntAct; Q09260; 3.
DR STRING; 6239.C32A3.1a; -.
DR EPD; Q09260; -.
DR PaxDb; Q09260; -.
DR EnsemblMetazoa; C32A3.1a.1; C32A3.1a.1; WBGene00004765. [Q09260-1]
DR EnsemblMetazoa; C32A3.1b.1; C32A3.1b.1; WBGene00004765. [Q09260-2]
DR GeneID; 175464; -.
DR UCSC; C32A3.1b.2; c. elegans. [Q09260-1]
DR CTD; 175464; -.
DR WormBase; C32A3.1a; CE27810; WBGene00004765; sel-8. [Q09260-1]
DR WormBase; C32A3.1b; CE01505; WBGene00004765; sel-8. [Q09260-2]
DR eggNOG; ENOG502QRT9; Eukaryota.
DR HOGENOM; CLU_696827_0_0_1; -.
DR InParanoid; Q09260; -.
DR OMA; HTPFANI; -.
DR OrthoDB; 1557766at2759; -.
DR SignaLink; Q09260; -.
DR EvolutionaryTrace; Q09260; -.
DR PRO; PR:Q09260; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00004765; Expressed in embryo and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:WormBase.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:WormBase.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:WormBase.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:WormBase.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IMP:UniProtKB.
DR DisProt; DP02378; -.
DR IDEAL; IID50087; -.
DR InterPro; IPR021587; Transcription_activator_LAG-3.
DR Pfam; PF11498; Activator_LAG-3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Notch signaling pathway;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..490
FT /note="Protein lag-3"
FT /id="PRO_0000084353"
FT REGION 18..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 105..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..22
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:10830967"
FT /id="VSP_003908"
FT MUTAGEN 409..490
FT /note="Missing: In sa54; suppresses the phenotype of a lin-
FT 12 mutation that induces constitutive activity upon lin-
FT 12."
FT /evidence="ECO:0000269|PubMed:10884418"
FT HELIX 60..83
FT /evidence="ECO:0007829|PDB:2FO1"
FT HELIX 85..98
FT /evidence="ECO:0007829|PDB:2FO1"
FT HELIX 100..112
FT /evidence="ECO:0007829|PDB:2FO1"
SQ SEQUENCE 490 AA; 56482 MW; 396A6C194C382A07 CRC64;
MDDLSEFFVI EEMFISEPSV AGMKPSTSKT THSPPPEEPT APFVNDNLPN PEDEPTIGDL
NAFHSGEELH RQRSELARAN YEKARPEMIA NQRAVTAHLF NRYTEDEERK RVEQQKNKEA
MNASTSAPTS SRNGGQSVEN RKRRNDVVVA PPTSEEEWKR AQQQHWMGQQ QPQMQFQMQQ
QYHSQQQQYI MMQQQHHHMT GMQQIHHQMP STSSADSIRS VPTPASSMHQ PSPAEMRNGC
GMSRNATMDM TCSPMSGGQP IVDENNLAVP EGEWFDKLAL AVAEQYNVDT ILGPDTYDTF
LAELDFSSSE SPTKQSPMEM NGDRMPSTAP PPAQNPQHIA QLQQQQNKMR LMQQQQQEMQ
RIEQQRRQQI MQQQQQQQQQ EHQRQQMLLQ QQQQQQQMQQ HHQMNGGGQF ATQAHQQAAY
MQQMQRMEQI RHQQQQAQQH QQAQQQHQQQ AQHHQMGYGI PNGYPQQMHM HPPAYGAHHM
PQPTAFANIN
