MXL3_CAEEL
ID MXL3_CAEEL Reviewed; 235 AA.
AC Q18711;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Protein mxl-3 {ECO:0000305};
DE AltName: Full=Basic-helix-loop-helix transcription factor 3 {ECO:0000303|PubMed:23604316};
DE AltName: Full=Max-like protein 3 {ECO:0000312|WormBase:F46G10.6};
GN Name=mxl-3 {ECO:0000312|WormBase:F46G10.6};
GN Synonyms=hlh-23 {ECO:0000312|WormBase:F46G10.6};
GN ORFNames=F46G10.6 {ECO:0000312|WormBase:F46G10.6};
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|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 [2] {ECO:0000305}
RP FUNCTION, AND SUBUNIT.
RX PubMed=19632181; DOI=10.1016/j.cell.2009.04.058;
RA Grove C.A., De Masi F., Barrasa M.I., Newburger D.E., Alkema M.J.,
RA Bulyk M.L., Walhout A.J.M.;
RT "A multiparameter network reveals extensive divergence between C. elegans
RT bHLH transcription factors.";
RL Cell 138:314-327(2009).
RN [3] {ECO:0000305}
RP INTERACTION WITH SKN-1.
RX PubMed=23040073; DOI=10.1016/j.cmet.2012.09.007;
RA Paek J., Lo J.Y., Narasimhan S.D., Nguyen T.N., Glover-Cutter K.,
RA Robida-Stubbs S., Suzuki T., Yamamoto M., Blackwell T.K., Curran S.P.;
RT "Mitochondrial SKN-1/Nrf mediates a conserved starvation response.";
RL Cell Metab. 16:526-537(2012).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=23604316; DOI=10.1038/ncb2741;
RA O'Rourke E.J., Ruvkun G.;
RT "MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to
RT nutrient availability.";
RL Nat. Cell Biol. 15:668-676(2013).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=27487365; DOI=10.1371/journal.pgen.1006237;
RA Gruner M., Grubbs J., McDonagh A., Valdes D., Winbush A.,
RA van der Linden A.M.;
RT "Cell-Autonomous and Non-Cell-Autonomous Regulation of a Feeding State-
RT Dependent Chemoreceptor Gene via MEF-2 and bHLH Transcription Factors.";
RL PLoS Genet. 12:E1006237-E1006237(2016).
RN [6] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29113111; DOI=10.3390/genes8110307;
RA Mejia-Martinez F., Franco-Juarez B., Moreno-Arriola E.,
RA Hernandez-Vazquez A., Martinez-Avila M., Gomez-Manzo S., Marcial-Quino J.,
RA Carvajal K., Velazquez-Arellano A., Ortega-Cuellar D.;
RT "The MXL-3/SBP-1 Axis Is Responsible for Glucose-Dependent Fat Accumulation
RT in C. elegans.";
RL Genes (Basel) 8:0-0(2017).
CC -!- FUNCTION: Transcription factor which regulates the expression of genes
CC involved in lipid metabolism in response to nutrient availability
CC (PubMed:23604316, PubMed:29113111). Binds to the E-box motif 5'-CACGTG-
CC 3' (PubMed:19632181). Under well-fed conditions, binds to the promoter
CC and represses the expression of lipase genes lipl-1, lipl-2, lipl-3 and
CC to a lesser extent lipl-5, thereby preventing lipolysis
CC (PubMed:23604316). In response to a high-glucose diet, promotes fatty
CC acid synthesis, elongation and desaturation by up-regulating
CC transcription factor sbp-1 expression (PubMed:29113111). Under well-fed
CC conditions, acts remotely in the intestine to up-regulate the
CC expression of chemoreceptor srh-234 gene in the ADL sensory neuron,
CC possibly by regulating the insulin signaling pathway (PubMed:27487365).
CC {ECO:0000269|PubMed:19632181, ECO:0000269|PubMed:23604316,
CC ECO:0000269|PubMed:27487365, ECO:0000269|PubMed:29113111}.
CC -!- SUBUNIT: May form homodimer (PubMed:19632181). Interacts (via N-
CC terminus) with skn-1 isoforms a and c (PubMed:23040073).
CC {ECO:0000269|PubMed:19632181, ECO:0000269|PubMed:23040073}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23604316,
CC ECO:0000269|PubMed:29113111}. Cytoplasm {ECO:0000269|PubMed:29113111}.
CC Note=In response to nutrient levels, shuttles between the cytoplasm and
CC the nucleus (PubMed:29113111). Localizes to the nucleus in response to
CC high glucose levels (PubMed:29113111). {ECO:0000269|PubMed:29113111}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestine and in the AWC sensory
CC neurons. {ECO:0000269|PubMed:23604316}.
CC -!- INDUCTION: Down-regulated by fasting. {ECO:0000269|PubMed:23604316}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a depletion of fat
CC stores. RNAi-mediated knockdown in the intestine causes a fasting-like
CC transcriptional response, characterized by the up-regulation of the
CC lipl-1 gene transcription. {ECO:0000269|PubMed:23604316}.
CC -!- SIMILARITY: Belongs to the MAX family. {ECO:0000305}.
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DR EMBL; BX284606; CAA94125.1; -; Genomic_DNA.
DR PIR; T20079; T20079.
DR RefSeq; NP_510223.1; NM_077822.4.
DR AlphaFoldDB; Q18711; -.
DR IntAct; Q18711; 11.
DR STRING; 6239.F46G10.6; -.
DR PaxDb; Q18711; -.
DR EnsemblMetazoa; F46G10.6.1; F46G10.6.1; WBGene00003511.
DR GeneID; 181457; -.
DR KEGG; cel:CELE_F46G10.6; -.
DR UCSC; F46G10.6; c. elegans.
DR CTD; 181457; -.
DR WormBase; F46G10.6; CE05882; WBGene00003511; mxl-3.
DR eggNOG; KOG2483; Eukaryota.
DR GeneTree; ENSGT00530000064011; -.
DR HOGENOM; CLU_1181134_0_0_1; -.
DR InParanoid; Q18711; -.
DR OMA; HIKDHFV; -.
DR OrthoDB; 1545748at2759; -.
DR SignaLink; Q18711; -.
DR PRO; PR:Q18711; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003511; Expressed in larva and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0071339; C:MLL1 complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:WormBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0007568; P:aging; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:WormBase.
DR GO; GO:0032094; P:response to food; IMP:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR037933; MAX-like.
DR PANTHER; PTHR10328; PTHR10328; 1.
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 Activator; Cytoplasm; DNA-binding; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..235
FT /note="Protein mxl-3"
FT /id="PRO_0000449317"
FT DOMAIN 47..98
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 18..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..60
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 61..98
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT COMPBIAS 18..33
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 235 AA; 26040 MW; 129F81D125B36998 CRC64;
MSAIVEDMYL LSSSMKMEKQ FRKRHHSDSS DDDSSSPKSA SPSMDDDRRA HHNELERRRR
DHIKDHFTIL KDAIPLLDGE KSSRALILKR AVEFIHVMQT KLSSQGKAIE DLTRKNELLE
ERLLERESSG SPSSSRLPAL AVSSSQMQLT MPIIPQMQNI AQLSQYPQQA NIIAQSTNPA
QLDGLIALNN DAILALLGSF QSVSPSLLDS APGTPPSGFY PCAFSPVDQQ MAVKI
