LIN14_CAEEL
ID LIN14_CAEEL Reviewed; 539 AA.
AC Q21446; Q21447; Q22775; Q27292;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Protein lin-14;
DE AltName: Full=Abnormal cell lineage protein 14;
GN Name=lin-14 {ECO:0000312|WormBase:T25C12.1a};
GN ORFNames=T25C12.1 {ECO:0000312|WormBase:T25C12.1a};
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 [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION,
RP ALTERNATIVE SPLICING (ISOFORMS A AND B), AND MUTAGENESIS OF ALA-322.
RC STRAIN=Bristol N2;
RX PubMed=1916264; DOI=10.1101/gad.5.10.1813;
RA Wightman B., Buerglin T.R., Gatto J., Arasu P., Ruvkun G.;
RT "Negative regulatory sequences in the lin-14 3'-untranslated region are
RT necessary to generate a temporal switch during Caenorhabditis elegans
RT development.";
RL Genes Dev. 5:1813-1824(1991).
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, AND TISSUE SPECIFICITY.
RC STRAIN=Bristol N2;
RX PubMed=1916265; DOI=10.1101/gad.5.10.1825;
RA Arasu P., Wightman B., Ruvkun G.;
RT "Temporal regulation of lin-14 by the antagonistic action of two other
RT heterochronic genes, lin-4 and lin-28.";
RL Genes Dev. 5:1825-1833(1991).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ARG-303.
RX PubMed=12490565; DOI=10.1242/dev.00277;
RA Aurelio O., Boulin T., Hobert O.;
RT "Identification of spatial and temporal cues that regulate postembryonic
RT expression of axon maintenance factors in the C. elegans ventral nerve
RT cord.";
RL Development 130:599-610(2003).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Bristol N2;
RX PubMed=16314527; DOI=10.1128/mcb.25.24.11059-11072.2005;
RA Hristova M., Birse D., Hong Y., Ambros V.;
RT "The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel
RT transcription factor that controls the developmental timing of
RT transcription from the insulin/insulin-like growth factor gene ins-33 by
RT direct DNA binding.";
RL Mol. Cell. Biol. 25:11059-11072(2005).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLY-381.
RC STRAIN=Bristol N2;
RX PubMed=19161245; DOI=10.1002/dvdy.21837;
RA Johnson R.W., Liu L.Y., Hanna-Rose W., Chamberlin H.M.;
RT "The Caenorhabditis elegans heterochronic gene lin-14 coordinates temporal
RT progression and maturation in the egg-laying system.";
RL Dev. Dyn. 238:394-404(2009).
RN [7]
RP FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=20951046; DOI=10.1016/j.cub.2010.09.055;
RA Li J., Greenwald I.;
RT "LIN-14 inhibition of LIN-12 contributes to precision and timing of C.
RT elegans vulval fate patterning.";
RL Curr. Biol. 20:1875-1879(2010).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF ARG-303.
RX PubMed=21471153; DOI=10.1242/dev.057109;
RA Huang X., Zhang H., Zhang H.;
RT "The zinc-finger protein SEA-2 regulates larval developmental timing and
RT adult lifespan in C. elegans.";
RL Development 138:2059-2068(2011).
RN [9]
RP PROTEOLYTIC CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=25432023; DOI=10.7554/elife.04265;
RA Weaver B.P., Zabinsky R., Weaver Y.M., Lee E.S., Xue D., Han M.;
RT "CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression
RT dynamics for robust development in C. elegans.";
RL Elife 3:E04265-E04265(2014).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-303.
RX PubMed=26811380; DOI=10.1242/dev.132738;
RA Herrera R.A., Kiontke K., Fitch D.H.;
RT "Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-
RT to-adult transition in Caenorhabditis elegans.";
RL Development 143:799-809(2016).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-303.
RX PubMed=28250105; DOI=10.1098/rsob.160313;
RA Borbolis F., Flessa C.M., Roumelioti F., Diallinas G., Stravopodis D.J.,
RA Syntichaki P.;
RT "Neuronal function of the mRNA decapping complex determines survival of
RT Caenorhabditis elegans at high temperature through temporal regulation of
RT heterochronic gene expression.";
RL Open Biol. 7:0-0(2017).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30956008; DOI=10.1016/j.devcel.2019.03.003;
RA Kiontke K.C., Herrera R.A., Vuong E., Luo J., Schwarz E.M., Fitch D.H.A.,
RA Portman D.S.;
RT "The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by
RT Destabilizing LIN-28.";
RL Dev. Cell 49:542-555(2019).
CC -!- FUNCTION: Heterochronic protein which controls the choice of stage
CC specific cell fates. Involved in the temporal progression of vulval
CC fate patterning, possibly by inhibiting lin-12. Acts as a transcription
CC factor involved in the stage-specific repression of insulin/insulin-
CC like growth factor gene ins-33. Plays a role in governing the
CC developmental timining of male tail tip morphogenesis (PubMed:26811380,
CC PubMed:30956008). Plays a role in controlling the timing of seam cell
CC development during the larval stages (PubMed:21471153). Plays a role in
CC promoting survival at high temperatures in larvae (PubMed:28250105).
CC Involved in maintenance of the architecture of the ventral nerve cord,
CC perhaps acting via modulating expression of the immunoglobulin domain
CC gene zig-4. {ECO:0000269|PubMed:12490565, ECO:0000269|PubMed:16314527,
CC ECO:0000269|PubMed:19161245, ECO:0000269|PubMed:1916265,
CC ECO:0000269|PubMed:20951046, ECO:0000269|PubMed:21471153,
CC ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:28250105,
CC ECO:0000269|PubMed:30956008}.
CC -!- FUNCTION: [Isoform a]: May specify L2 and later cell fates, creating a
CC temporal switch. {ECO:0000269|PubMed:1916264}.
CC -!- FUNCTION: [Isoform b]: May be involved in specifying L1 cell fates.
CC {ECO:0000269|PubMed:1916264}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16314527,
CC ECO:0000269|PubMed:19161245, ECO:0000269|PubMed:1916264,
CC ECO:0000269|PubMed:1916265}. Note=May associate with mitotic
CC chromosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:T25C12.1a}; Synonyms=B1
CC {ECO:0000303|PubMed:1916264};
CC IsoId=Q21446-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T25C12.1b}; Synonyms=A
CC {ECO:0000303|PubMed:1916264};
CC IsoId=Q21446-2; Sequence=VSP_004306;
CC -!- TISSUE SPECIFICITY: High levels in hypodermal, intestinal, body wall
CC muscle, nerve ring, and ventral nerve cord cells of embryos and L1
CC animals. {ECO:0000269|PubMed:1916265}.
CC -!- DEVELOPMENTAL STAGE: Present at high levels in embryos and L1 animals
CC but is undetectable at later stages.
CC -!- PTM: Cleaved by caspase ced-3 in vitro. {ECO:0000269|PubMed:25432023}.
CC -!- DISRUPTION PHENOTYPE: Asynchrony between gonadal and vulval
CC development. Retarded uterine uv1 cell differentiation
CC (PubMed:19161245). RNAi-mediated knockdown results in the precocious
CC onset of tail tip retraction resulting in over-retracted and shortened
CC adult male tails (also known as the Ore phenotype) (PubMed:26811380,
CC PubMed:30956008). RNAi-mediated knockdown in a ced-3 and ain-1 double
CC mutant background reduces the percentage of animals with developmental
CC defects including impaired egg-laying and production of ectopic seam
CC cells (PubMed:25432023). RNAi-mediated knockdown reduced the number of
CC dauer animals in a dcap-1 mutant background (PubMed:28250105).
CC {ECO:0000269|PubMed:19161245, ECO:0000269|PubMed:25432023,
CC ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:28250105,
CC ECO:0000269|PubMed:30956008}.
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DR EMBL; X60231; CAA42791.1; -; Genomic_DNA.
DR EMBL; X60232; CAA42791.1; JOINED; Genomic_DNA.
DR EMBL; X60233; CAA42791.1; JOINED; Genomic_DNA.
DR EMBL; X60232; CAA42792.1; -; Genomic_DNA.
DR EMBL; X60233; CAA42792.1; JOINED; Genomic_DNA.
DR EMBL; X60233; CAA42793.1; -; Genomic_DNA.
DR EMBL; BX284606; CAA91484.2; -; Genomic_DNA.
DR EMBL; BX284606; CAA91485.1; -; Genomic_DNA.
DR PIR; A40581; A40581.
DR PIR; B89648; B89648.
DR PIR; T25268; T25268.
DR RefSeq; NP_509916.2; NM_077515.2. [Q21446-1]
DR RefSeq; NP_509917.1; NM_077516.3. [Q21446-2]
DR AlphaFoldDB; Q21446; -.
DR BioGRID; 46246; 1.
DR STRING; 6239.T25C12.1a; -.
DR iPTMnet; Q21446; -.
DR EPD; Q21446; -.
DR PaxDb; Q21446; -.
DR PeptideAtlas; Q21446; -.
DR EnsemblMetazoa; T25C12.1a.1; T25C12.1a.1; WBGene00003003. [Q21446-1]
DR EnsemblMetazoa; T25C12.1b.1; T25C12.1b.1; WBGene00003003. [Q21446-2]
DR GeneID; 181337; -.
DR KEGG; cel:CELE_T25C12.1; -.
DR UCSC; T25C12.1a; c. elegans. [Q21446-1]
DR CTD; 181337; -.
DR WormBase; T25C12.1a; CE43285; WBGene00003003; lin-14. [Q21446-1]
DR WormBase; T25C12.1b; CE03734; WBGene00003003; lin-14. [Q21446-2]
DR eggNOG; ENOG502S18Y; Eukaryota.
DR HOGENOM; CLU_520958_0_0_1; -.
DR InParanoid; Q21446; -.
DR OMA; PIFPFPQ; -.
DR OrthoDB; 796674at2759; -.
DR PRO; PR:Q21446; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003003; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:WormBase.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0048666; P:neuron development; IMP:WormBase.
DR GO; GO:0042659; P:regulation of cell fate specification; IGI:UniProtKB.
DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:UniProtKB.
DR GO; GO:0090444; P:regulation of nematode larval development, heterochronic; IMP:WormBase.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..539
FT /note="Protein lin-14"
FT /id="PRO_0000084425"
FT REGION 162..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..64
FT /note="MGKGQPKEPKIEQSVVDLCKRTVAMNLLQCYPTTTVDEMNCEEWGNGTESTQ
FT SVAACQGCIELR -> MDLPGTSSNDFVQPFSTFYPSPTSPPMHQAALLPALTALYPQL
FT LQLPHLKSDYLIRSDMSAF (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_004306"
FT MUTAGEN 303
FT /note="R->G: In n179; precocious onset of tail tip
FT retraction resulting in over-retracted and shortened adult
FT male tails (also known as the Ore phenotype). Premature
FT alae formation at the L3 larval stage. Premature alae
FT formation is partially suppressed in a sea-2 bp283 mutant
FT background. Enhances the precocious development, semi-
FT dumpy, vulval protrusions and egg-laying defects in a dcap-
FT 1 tm3163 mutant background at 25 degrees Celsius. Partially
FT suppresses the enhanced dauer phenotype of dcap-1 tm3163
FT mutants at 25 degrees Celsius. Abolishes expression of the
FT immunoglobulin domain gene zig-4 in the interneuron PVT
FT during the L1 larval stage."
FT /evidence="ECO:0000269|PubMed:12490565,
FT ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:26811380,
FT ECO:0000269|PubMed:28250105"
FT MUTAGEN 322
FT /note="A->T: In n838; decrease in protein levels."
FT /evidence="ECO:0000269|PubMed:1916264"
FT MUTAGEN 381
FT /note="G->D: In sa485; alteration of vulval-gonadal
FT synchrony."
FT /evidence="ECO:0000269|PubMed:19161245"
FT CONFLICT 1..24
FT /note="Missing (in Ref. 1; CAA42792)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 539 AA; 59343 MW; 8939AE7F5D11E72E CRC64;
MGKGQPKEPK IEQSVVDLCK RTVAMNLLQC YPTTTVDEMN CEEWGNGTES TQSVAACQGC
IELRKEVTDL RQAVNLILPM LPLYPTIGNG FNATGLAAQP TLQHVIQQSL LRKRPVAQTP
TVPQPECPGQ IRPVLSSPAA ALQNVIMLNP WIMGSSLKPA SPTLPNGQIP TTIGETSLQG
TDDQTVKWIG PSSVDSNGQK TDSSAASAGD NQNIDVIGDG SESPTSSNHS AQEIALMTSQ
QTFLNALKDS SFLFTNPVPT VETAPPLRVA PPINGTTNGT AKAGGPERKP RKPVNDDIVK
IVRNQDLSEE NISMFEIPVP KAIASDPTFR PVSEQQIIQQ IIQGKKYEEM EVGECMIQLC
KKLAEKRVFG PRLMSQTTVA GLNHSNYANL PIKGICYIQH VCRKVLYDKF ENEEDFWDKF
REAMRKLAAR CRRVRHAKKT KHNREEAQAE MLSKRYGEDM PFNLNGAGLI RPKVETVSPE
ANILNSDQIK SQLESLFAHI PKTESETPLI EIIQQNISLF THLIRTKVES QSPPLQGPQ
