MDL1_CAEEL
ID MDL1_CAEEL Reviewed; 281 AA.
AC G5EG44;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Mad-like protein 1 {ECO:0000303|PubMed:9764821};
GN Name=mdl-1 {ECO:0000312|WormBase:R03E9.1};
GN ORFNames=R03E9.1 {ECO:0000312|WormBase:R03E9.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAB40927.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB40927.1};
RX PubMed=9764821; DOI=10.1038/sj.onc.1202036;
RA Yuan J., Tirabassi R.S., Bush A.B., Cole M.D.;
RT "The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for
RT vertebrate MAD and MAX.";
RL Oncogene 17:1109-1118(1998).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24699255; DOI=10.1371/journal.pgen.1004278;
RA Johnson D.W., Llop J.R., Farrell S.F., Yuan J., Stolzenburg L.R.,
RA Samuelson A.V.;
RT "The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse
RT longevity signals.";
RL PLoS Genet. 10:e1004278-e1004278(2014).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=27402359; DOI=10.1534/g3.116.029983;
RA Botts M.R., Cohen L.B., Probert C.S., Wu F., Troemel E.R.;
RT "Microsporidia Intracellular Development Relies on Myc Interaction Network
RT Transcription Factors in the Host.";
RL G3 (Bethesda) 6:2707-2716(2016).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=27001890; DOI=10.1038/ncomms10944;
RA Nakamura S., Karalay O., Jaeger P.S., Horikawa M., Klein C., Nakamura K.,
RA Latza C., Templer S.E., Dieterich C., Antebi A.;
RT "Mondo complexes regulate TFEB via TOR inhibition to promote longevity in
RT response to gonadal signals.";
RL Nat. Commun. 7:10944-10944(2016).
CC -!- FUNCTION: Transcriptional regulator which binds to the E box motif 5'-
CC CACGTG-3', when in a heterodimeric complex with mxl-1 (PubMed:9764821).
CC Involved in the control of lifespan in response to dietary restriction,
CC the decline in protein homeostasis associated with normal aging,
CC germline signaling and may overlap with the insulin-like signaling
CC pathway (PubMed:24699255, PubMed:27001890). Plays a role in autophagy
CC (PubMed:27001890). Involved in promoting infection by the
CC microsporidian pathogen N.parisii, possibly together with transcription
CC factors pha-4 and zip-10 (PubMed:27402359).
CC {ECO:0000269|PubMed:24699255, ECO:0000269|PubMed:27001890,
CC ECO:0000269|PubMed:27402359, ECO:0000269|PubMed:9764821}.
CC -!- SUBUNIT: Heterodimer with mxl-1 in presence and absence of DNA.
CC {ECO:0000269|PubMed:9764821}.
CC -!- INTERACTION:
CC G5EG44; G5EEH5: mxl-1; NbExp=5; IntAct=EBI-1182971, EBI-1182982;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:27402359}.
CC -!- TISSUE SPECIFICITY: Expressed in intestinal cells in adults.
CC {ECO:0000269|PubMed:27402359}.
CC -!- DEVELOPMENTAL STAGE: Expressed weakly in larval stage L1 and strongly
CC throughout the remainder of larval development (PubMed:9764821).
CC Expressed in larval posterior intestinal cells and neurons
CC (PubMed:9764821, PubMed:27402359). {ECO:0000269|PubMed:27402359,
CC ECO:0000269|PubMed:9764821}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown increases lifespan, which
CC is abolished on an mxl-2 or mml-1 mutant background, or by simultaneous
CC RNAi-mediated knockdown of daf-16 or pha-4 (PubMed:24699255). RNAi-
CC mediated knockdown causes delayed onset of polyglutamine-mediated
CC paralysis (PubMed:24699255). RNAi-mediated knockdown reduces spore
CC levels of the microsporidian pathogen N.parisii during infection,
CC further reduced on an mxl-2 mutant background (PubMed:27402359).
CC {ECO:0000269|PubMed:24699255, ECO:0000269|PubMed:27402359}.
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DR EMBL; U82968; AAB40927.1; -; mRNA.
DR EMBL; BX284606; CCD72421.1; -; Genomic_DNA.
DR PIR; T28857; T28857.
DR RefSeq; NP_509136.1; NM_076735.5.
DR AlphaFoldDB; G5EG44; -.
DR SMR; G5EG44; -.
DR IntAct; G5EG44; 3.
DR STRING; 6239.R03E9.1; -.
DR EPD; G5EG44; -.
DR PaxDb; G5EG44; -.
DR EnsemblMetazoa; R03E9.1.1; R03E9.1.1; WBGene00003163.
DR GeneID; 180942; -.
DR KEGG; cel:CELE_R03E9.1; -.
DR CTD; 180942; -.
DR WormBase; R03E9.1; CE04784; WBGene00003163; mdl-1.
DR eggNOG; KOG2483; Eukaryota.
DR GeneTree; ENSGT00940000170386; -.
DR HOGENOM; CLU_984270_0_0_1; -.
DR InParanoid; G5EG44; -.
DR OMA; CYPRISM; -.
DR OrthoDB; 1632634at2759; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003163; Expressed in larva and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005667; C:transcription regulator complex; IPI:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:WormBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0045595; P:regulation of cell differentiation; IGI:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Coiled coil; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..281
FT /note="Mad-like protein 1"
FT /id="PRO_0000451996"
FT DOMAIN 95..147
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 71..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..108
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 109..147
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 189..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 144..185
FT /evidence="ECO:0000255"
FT COMPBIAS 71..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 281 AA; 30738 MW; DBC6A8C3919CA001 CRC64;
MEQQLNLGHL LTAARLLDIG ALDISSLDLG ALTSTSSSPG SSSPAMFDLS NESELRSLFC
GKLKVDKKQS SCASNASTSS QPYCSSPPAR KSSKHSRTAH NELEKTRRAN LRGCLETLKM
LVPCVSDATR NTTLALLTRA RDHIIELQDS NAAQMKKLND LRDEQDELVA ELAQLQADEE
VAQATSQACQ TLSQSRPESR ASSFTSTSSR DSPCYLEYSP SSKPMDSHKP TIIDLYAEGL
IPRGPITFPR PLVYPHNVFD LMNLPPTPFD VSQFLPINLQ V
