WBS14_CAEEL
ID WBS14_CAEEL Reviewed; 1009 AA.
AC P41846; Q9BKE3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Protein WBSCR14 homolog;
DE AltName: Full=MLX interactor;
GN Name=mml-1; Synonyms=mio; ORFNames=T20B12.6;
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].
RC STRAIN=Bristol N2;
RA Yuan J., Hamelin M., Yu L., Lubeck O., Hull R., Savage-Dunn C., Blevins R.;
RT "The C. elegans Williams Beuren syndrome WBSCR14 homolog: a potential
RT nematode Myc.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11230181; DOI=10.1093/hmg/10.6.617;
RA Cairo S., Merla G., Urbinati F., Ballabio A., Reymond A.;
RT "WBSCR14, a gene mapping to the Williams-Beuren syndrome deleted region, is
RT a new member of the Mlx transcription factor network.";
RL Hum. Mol. Genet. 10:617-627(2001).
RN [3]
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=17826759; DOI=10.1016/j.ydbio.2007.07.034;
RA Pickett C.L., Breen K.T., Ayer D.E.;
RT "A C. elegans Myc-like network cooperates with semaphorin and Wnt signaling
RT pathways to control cell migration.";
RL Dev. Biol. 310:226-239(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, 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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP 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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
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: Transcription factor that binds to the E box motif 5'-CACGTG-
CC 3', probably in a heterodimeric complex with mxl-2 (PubMed:17826759).
CC Involved in modulating longevity in response to TOR signaling, dietary
CC restriction, the decline in protein homeostasis associated with normal
CC aging, germline signaling and the insulin-like signaling pathway
CC (PubMed:24699255, PubMed:27001890). Plays a role in autophagy
CC (PubMed:27001890). Involved in regulating migration of the ray 1
CC precursor cells in the male tail, acting in concert with Wnt and
CC semaphorin signaling pathways (PubMed:17826759). Regulates
CC transcription of genes encoding extracellular matrix (ECM) components
CC which may contribute to the substratum required for migration of the
CC neighboring ray 1 precursor cells (PubMed:17826759). Involved in
CC repressing infection by the microsporidian pathogen N.parisii, probably
CC acting independently of its canonical partner, mxl-2 (PubMed:27402359).
CC {ECO:0000269|PubMed:17826759, ECO:0000269|PubMed:24699255,
CC ECO:0000269|PubMed:27001890, ECO:0000269|PubMed:27402359}.
CC -!- INTERACTION:
CC P41846; Q9TZ70: mxl-2; NbExp=3; IntAct=EBI-2408887, EBI-2408874;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:17826759, ECO:0000269|PubMed:24699255,
CC ECO:0000269|PubMed:27402359}. Cytoplasm {ECO:0000269|PubMed:24699255}.
CC Mitochondrion {ECO:0000269|PubMed:27001890}. Note=Nuclear localization
CC is promoted by conditions of dietary restriction or reduced insulin-
CC like/IGF-1 signaling in a pha-4-dependent manner.
CC {ECO:0000269|PubMed:24699255}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine, neurons, muscle,
CC hypodermis, excretory cell and other tissues.
CC {ECO:0000269|PubMed:27001890, ECO:0000269|PubMed:27402359}.
CC -!- DEVELOPMENTAL STAGE: Expressed in epidermal cells as early as the 50-
CC 100 cell stage of embryogenesis and in intestinal cells at the 4E stage
CC (PubMed:17826759). Expressed in non-migratory, syncytial epidermis at
CC larval stage L1 (PubMed:17826759). {ECO:0000269|PubMed:17826759}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown reduces lifespan, which
CC is further reduced on daf-2 or glp-1 mutant backgrounds
CC (PubMed:24699255, PubMed:27001890). RNAi-mediated knockdown causes
CC premature onset of polyglutamine-mediated paralysis (PubMed:24699255).
CC RNAi-mediated knockdown increases spore levels of the microsporidian
CC pathogen N.parisii during infection, on an mxl-2 or mdl-1 mutant
CC background (PubMed:27402359). {ECO:0000269|PubMed:24699255,
CC ECO:0000269|PubMed:27001890, ECO:0000269|PubMed:27402359}.
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; AF213473; AAL50027.1; -; mRNA.
DR EMBL; AF264757; AAK20949.1; -; mRNA.
DR EMBL; FO081094; CCD69075.1; -; Genomic_DNA.
DR PIR; T16906; T16906.
DR RefSeq; NP_498631.2; NM_066230.4.
DR AlphaFoldDB; P41846; -.
DR SMR; P41846; -.
DR BioGRID; 41259; 11.
DR IntAct; P41846; 8.
DR STRING; 6239.T20B12.6a; -.
DR iPTMnet; P41846; -.
DR EPD; P41846; -.
DR PaxDb; P41846; -.
DR PeptideAtlas; P41846; -.
DR PRIDE; P41846; -.
DR EnsemblMetazoa; T20B12.6a.1; T20B12.6a.1; WBGene00003378.
DR GeneID; 176050; -.
DR KEGG; cel:CELE_T20B12.6; -.
DR UCSC; T20B12.6a; c. elegans.
DR CTD; 176050; -.
DR WormBase; T20B12.6a; CE30186; WBGene00003378; mml-1.
DR eggNOG; KOG3582; Eukaryota.
DR HOGENOM; CLU_007471_0_0_1; -.
DR InParanoid; P41846; -.
DR OMA; QTCQTYQ; -.
DR OrthoDB; 388166at2759; -.
DR PhylomeDB; P41846; -.
DR Reactome; R-CEL-163358; PKA-mediated phosphorylation of key metabolic factors.
DR Reactome; R-CEL-163765; ChREBP activates metabolic gene expression.
DR SignaLink; P41846; -.
DR PRO; PR:P41846; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00003378; Expressed in embryo and 3 other tissues.
DR ExpressionAtlas; P41846; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005739; C:mitochondrion; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; 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 Cytoplasm; DNA-binding; Mitochondrion; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..1009
FT /note="Protein WBSCR14 homolog"
FT /id="PRO_0000127506"
FT DOMAIN 803..856
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 304..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 856..877
FT /note="Leucine-zipper"
FT COMPBIAS 325..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..704
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 1..96
FT /note="Missing (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 97..113
FT /note="KWKDFKGLRLHWKQRVR -> MEGFQRITSFIGSRGYD (in Ref. 1;
FT AAL50027)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="E -> G (in Ref. 1; AAL50027)"
FT /evidence="ECO:0000305"
FT CONFLICT 523..525
FT /note="QPQ -> HPN (in Ref. 1; AAL50027)"
FT /evidence="ECO:0000305"
FT CONFLICT 725
FT /note="E -> G (in Ref. 1; AAL50027)"
FT /evidence="ECO:0000305"
FT CONFLICT 729
FT /note="A -> T (in Ref. 1; AAL50027)"
FT /evidence="ECO:0000305"
FT CONFLICT 921
FT /note="N -> S (in Ref. 1; AAL50027)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1009 AA; 112859 MW; 5299415EBC3502FE CRC64;
MSRGQIIHSG HFMCSNPHDD LVQDEDEEDV EVDVVEDDDK SMEASSSVHH KNKALDEKPV
TFYKFGVGKT QSIAIDVSLN KLNKCIKVAY NKMTTPKWKD FKGLRLHWKQ RVRLNNVIWR
AYYIEFRKKQ PEKPKKPFCY FAVPDDDTTH QKIEGSIVEG MYWKRKMEGV CAQYKRWRIR
SKHNLVTDKG GMVATCSSTS VSSMTGELKR KRKHTVPKET IESKLRSYEP PVKLQRSQTP
KHTISDEFAW DFDDLDNVFT DDFLNSLSEP YMFPDPRDVY SGNNADIMQP GLLPLQPTIE
DIMMSLGDDM PDSPPFHNDR DTMRTPTNDQ PSISAQQIPQ MRRSASSSAS LHQMQVAQAQ
AQSISQISQP SQQLQHQIQI QQPVAARPHE FMASSIMMDY RLMPTRQSSA ITSQMLMLSQ
SASTLSSQPQ YATSTHYSTN NSFLPIRNTM TNQHHLGHTS QHSPWNKQQQ SNFLVSLPHQ
SHVERILNNQ PPLVPPPSRS NLLPTQNDPY LPQFLQSTQP TPQPQSHDPM MAPSRSWWLD
SPLTASVQSP LSVATPLPLA NQTGPQTPLG QLIGSADNGF LFGGNNTPGG FKMSGTTSGV
PTLSQRLEQP PISRTSTIFG NVENKPERIF TSLTSQNTPT PSPLDISSLS RLRTSSLNES
WKMSHIVEGS PTYQAFAASV TTKPSILESP STSGDISGPA SVPVQASQHP PKIITPPSAS
SKRKEQEAAM APLVNRQQSC DVNLLNGKMA VKVEEKSGRH YLPTTPTELK EVTKEEPLLM
SAPSSVKSMR RQAPDSTLHP EERKRILHLH AEQNRRSALK DGFDQLMDII PDLYSGGVKP
TNAVVLAKSA DHIRRLQAEK WDKTQKIDEA KAKIEKLNQK ITSLQSNLPQ SSAPSSSSQV
DSKTSLETFF DRYVKEGAKK NWRFWVMSQM LKPICVTQTN SFASSVAGDS SSRNEVAASC
SDWLNKNWKA TELRPLASTL LVSLATNSSI LAEPDTLPDY VMQQLKNPF
