HLH30_CAEEL
ID HLH30_CAEEL Reviewed; 524 AA.
AC H2KZZ2; A0A2X0RWL7; A0A2X0T4B7; H2KZZ0; H2KZZ1; H2KZZ3; H2KZZ4; Q5TYL0;
AC Q86MJ3; Q86MJ4;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Helix-loop-helix protein 30 {ECO:0000305};
GN Name=hlh-30 {ECO:0000312|WormBase:W02C12.3c};
GN ORFNames=W02C12.3 {ECO:0000312|WormBase:W02C12.3c};
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, SUBUNIT, AND TISSUE SPECIFICITY.
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
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 [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=23925298; DOI=10.1038/ncomms3267;
RA Lapierre L.R., De Magalhaes Filho C.D., McQuary P.R., Chu C.C.,
RA Visvikis O., Chang J.T., Gelino S., Ong B., Davis A.E., Irazoqui J.E.,
RA Dillin A., Hansen M.;
RT "The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in
RT Caenorhabditis elegans.";
RL Nat. Commun. 4:2267-2267(2013).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=24882217; DOI=10.1016/j.immuni.2014.05.002;
RA Visvikis O., Ihuegbu N., Labed S.A., Luhachack L.G., Alves A.M.,
RA Wollenberg A.C., Stuart L.M., Stormo G.D., Irazoqui J.E.;
RT "Innate host defense requires TFEB-mediated transcription of cytoprotective
RT and antimicrobial genes.";
RL Immunity 40:896-909(2014).
RN [6] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27184844; DOI=10.1016/j.celrep.2016.04.052;
RA Najibi M., Labed S.A., Visvikis O., Irazoqui J.E.;
RT "An evolutionarily conserved PLC-PKD-TFEB pathway for host defense.";
RL Cell Rep. 15:1728-1742(2016).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION 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).
RN [8] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27875098; DOI=10.1080/15548627.2016.1256933;
RA Chen H.D., Kao C.Y., Liu B.Y., Huang S.W., Kuo C.J., Ruan J.W., Lin Y.H.,
RA Huang C.R., Chen Y.H., Wang H.D., Aroian R.V., Chen C.S.;
RT "HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for
RT epithelium intrinsic cellular defense against bacterial pore-forming toxin
RT in C. elegans.";
RL Autophagy 13:371-385(2017).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28198373; DOI=10.1038/ncomms14337;
RA Kumsta C., Chang J.T., Schmalz J., Hansen M.;
RT "Hormetic heat stress and HSF-1 induce autophagy to improve survival and
RT proteostasis in C. elegans.";
RL Nat. Commun. 8:14337-14337(2017).
CC -!- FUNCTION: Transcription factor which regulates the expression of genes
CC involved in lipid metabolism and autophagy in response to nutrient
CC availability, bacterial pore-forming toxins or heat shock
CC (PubMed:23604316, PubMed:23925298, PubMed:27001890, PubMed:27875098,
CC PubMed:28198373). Binds to the E-box motif 5'-CACGTG-3'
CC (PubMed:19632181). Under fasting conditions, binds to the promoter and
CC activates the expression of lipase genes lipl-2, lipl-3 and lipl-5, and
CC to a lesser extent, lipl-1, thereby regulating lipolysis
CC (PubMed:23604316). Involved in modulating longevity in response to TOR
CC signaling, dietary restriction, germline signaling, heat shock and the
CC insulin-like signaling pathway (PubMed:23925298, PubMed:27001890,
CC PubMed:24882217, PubMed:28198373). Involved in the immune response to
CC infection by the S.aureus bacterium, probably acting downstream of the
CC protein kinase dkf-1, leading to the transcriptional activation of host
CC defense genes (PubMed:24882217, PubMed:27184844). May also play a role
CC in lysosomal biogenesis in response to nutrient availability
CC (PubMed:23604316). {ECO:0000269|PubMed:19632181,
CC ECO:0000269|PubMed:23604316, ECO:0000269|PubMed:23925298,
CC ECO:0000269|PubMed:24882217, ECO:0000269|PubMed:27001890,
CC ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27875098}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:19632181}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23604316,
CC ECO:0000269|PubMed:24882217, ECO:0000269|PubMed:28198373}. Cytoplasm
CC {ECO:0000269|PubMed:24882217, ECO:0000269|PubMed:28198373}.
CC Note=Localization to nucleus enhanced during fasting and on mutant
CC backgrounds involved in modulating longevity: glp-1, let-363 (tor),
CC eat-2, daf-2, clk-1 or rsks-1 (PubMed:23604316, PubMed:23925298).
CC Nuclear localization abolished on mml-1;glp-1 or mxl-2;glp-1 mutant
CC backgrounds (PubMed:27001890). Localization to nucleus enhanced as a
CC result of bacterial pore-forming toxin treatment, or heat shock
CC (PubMed:27875098, PubMed:28198373). {ECO:0000269|PubMed:23604316,
CC ECO:0000269|PubMed:23925298, ECO:0000269|PubMed:27001890,
CC ECO:0000269|PubMed:27875098}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24882217,
CC ECO:0000269|PubMed:27184844}. Note=(Microbial infection) Localization
CC to nucleus enriched rapidly after Staphylococcus aureus infection.
CC {ECO:0000269|PubMed:24882217, ECO:0000269|PubMed:27184844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=c {ECO:0000312|WormBase:W02C12.3c};
CC IsoId=H2KZZ2-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:W02C12.3a};
CC IsoId=H2KZZ2-2; Sequence=VSP_060892;
CC Name=b {ECO:0000312|WormBase:W02C12.3b};
CC IsoId=H2KZZ2-3; Sequence=VSP_060895;
CC Name=d {ECO:0000312|WormBase:W02C12.3d};
CC IsoId=H2KZZ2-4; Sequence=VSP_060893;
CC Name=e {ECO:0000312|WormBase:W02C12.3e};
CC IsoId=H2KZZ2-5; Sequence=VSP_060893, VSP_060895;
CC Name=f {ECO:0000312|WormBase:W02C12.3f};
CC IsoId=H2KZZ2-6; Sequence=VSP_060892, VSP_060895;
CC Name=g {ECO:0000312|WormBase:W02C12.3g};
CC IsoId=H2KZZ2-7; Sequence=VSP_060892, VSP_060896, VSP_060897;
CC Name=h {ECO:0000312|WormBase:W02C12.3h};
CC IsoId=H2KZZ2-8; Sequence=VSP_060891;
CC Name=i {ECO:0000312|WormBase:W02C12.3i};
CC IsoId=H2KZZ2-9; Sequence=VSP_060894;
CC Name=j {ECO:0000312|WormBase:W02C12.3j};
CC IsoId=H2KZZ2-10; Sequence=VSP_060894, VSP_060895;
CC -!- TISSUE SPECIFICITY: Expressed in the intestine and at lower levels in
CC other tissues, including the spermatheca and the vulva.
CC {ECO:0000269|PubMed:19632181, ECO:0000269|PubMed:23604316}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development
CC (PubMed:24882217). In L4 larvae and young adults, expression is highest
CC in the intestine, rectal epithelial cells, vulval epithelial cells,
CC spermathecae, and pharynx and absent from the gonads (PubMed:24882217).
CC {ECO:0000269|PubMed:24882217}.
CC -!- INDUCTION: Up-regulated by fasting. {ECO:0000269|PubMed:23604316}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in adults reduces
CC lifespan on eat-2, daf-2 and rsks-1 mutant backgrounds
CC (PubMed:23925298). RNAi-mediated knockdown during the fourth larval
CC stage reduces lifespan on a clk-1 mutant background (PubMed:23925298).
CC RNAi-mediated knockdown reduces the expression of mml-1 on a glp-1
CC mutant background (PubMed:27001890). RNAi-mediated knockdown increases
CC expression of lmp-1 and sqst-1 (PubMed:23925298).
CC {ECO:0000269|PubMed:23925298, ECO:0000269|PubMed:27001890}.
CC -!- SIMILARITY: Belongs to the MiT/TFE family. {ECO:0000305}.
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DR EMBL; BX284604; CCD70587.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70588.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70589.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70590.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70591.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70592.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70593.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70594.1; -; Genomic_DNA.
DR EMBL; BX284604; SPS41584.1; -; Genomic_DNA.
DR EMBL; BX284604; SPS41585.1; -; Genomic_DNA.
DR RefSeq; NP_001023411.1; NM_001028240.3. [H2KZZ2-1]
DR RefSeq; NP_001023412.1; NM_001028241.2.
DR RefSeq; NP_001023413.1; NM_001028242.3. [H2KZZ2-5]
DR RefSeq; NP_001023414.1; NM_001028243.1. [H2KZZ2-6]
DR RefSeq; NP_001023415.1; NM_001028244.3.
DR RefSeq; NP_001023416.1; NM_001028245.3.
DR RefSeq; NP_500461.1; NM_068060.3. [H2KZZ2-3]
DR RefSeq; NP_500462.1; NM_068061.3. [H2KZZ2-2]
DR AlphaFoldDB; H2KZZ2; -.
DR SMR; H2KZZ2; -.
DR IntAct; H2KZZ2; 4.
DR STRING; 6239.W02C12.3c; -.
DR EPD; H2KZZ2; -.
DR PaxDb; H2KZZ2; -.
DR EnsemblMetazoa; W02C12.3a.1; W02C12.3a.1; WBGene00020930. [H2KZZ2-2]
DR EnsemblMetazoa; W02C12.3a.2; W02C12.3a.2; WBGene00020930. [H2KZZ2-2]
DR EnsemblMetazoa; W02C12.3b.1; W02C12.3b.1; WBGene00020930. [H2KZZ2-3]
DR EnsemblMetazoa; W02C12.3c.1; W02C12.3c.1; WBGene00020930. [H2KZZ2-1]
DR EnsemblMetazoa; W02C12.3d.1; W02C12.3d.1; WBGene00020930. [H2KZZ2-4]
DR EnsemblMetazoa; W02C12.3d.2; W02C12.3d.2; WBGene00020930. [H2KZZ2-4]
DR EnsemblMetazoa; W02C12.3e.1; W02C12.3e.1; WBGene00020930. [H2KZZ2-5]
DR EnsemblMetazoa; W02C12.3f.1; W02C12.3f.1; WBGene00020930. [H2KZZ2-6]
DR EnsemblMetazoa; W02C12.3g.1; W02C12.3g.1; WBGene00020930. [H2KZZ2-7]
DR EnsemblMetazoa; W02C12.3h.1; W02C12.3h.1; WBGene00020930. [H2KZZ2-8]
DR EnsemblMetazoa; W02C12.3h.2; W02C12.3h.2; WBGene00020930. [H2KZZ2-8]
DR EnsemblMetazoa; W02C12.3i.1; W02C12.3i.1; WBGene00020930. [H2KZZ2-9]
DR EnsemblMetazoa; W02C12.3j.1; W02C12.3j.1; WBGene00020930. [H2KZZ2-10]
DR GeneID; 177157; -.
DR UCSC; W02C12.3g.1; c. elegans.
DR CTD; 177157; -.
DR WormBase; W02C12.3a; CE14416; WBGene00020930; hlh-30.
DR WormBase; W02C12.3b; CE28499; WBGene00020930; hlh-30.
DR WormBase; W02C12.3c; CE33712; WBGene00020930; hlh-30.
DR WormBase; W02C12.3d; CE33713; WBGene00020930; hlh-30.
DR WormBase; W02C12.3e; CE33714; WBGene00020930; hlh-30.
DR WormBase; W02C12.3f; CE33715; WBGene00020930; hlh-30.
DR WormBase; W02C12.3g; CE33716; WBGene00020930; hlh-30.
DR WormBase; W02C12.3h; CE37725; WBGene00020930; hlh-30.
DR WormBase; W02C12.3i; CE52661; WBGene00020930; hlh-30.
DR WormBase; W02C12.3j; CE52676; WBGene00020930; hlh-30.
DR eggNOG; KOG1318; Eukaryota.
DR GeneTree; ENSGT00940000169135; -.
DR HOGENOM; CLU_033106_0_0_1; -.
DR InParanoid; H2KZZ2; -.
DR OMA; DDPMISA; -.
DR OrthoDB; 1211990at2759; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00020930; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; H2KZZ2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:WormBase.
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:0097237; P:cellular response to toxic substance; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:1905686; P:positive regulation of plasma membrane repair; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:WormBase.
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 Alternative splicing; Coiled coil; Cytoplasm; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..524
FT /note="Helix-loop-helix protein 30"
FT /id="PRO_0000452002"
FT DOMAIN 263..316
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 170..214
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..276
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 277..316
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT COILED 316..350
FT /evidence="ECO:0000255"
FT COMPBIAS 21..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..163
FT /note="Missing (in isoform h)"
FT /id="VSP_060891"
FT VAR_SEQ 1..122
FT /note="MIRQLNSPGGGGGLGLNNPRAQQPPGAQQQQQPQQAQQQFYDDEPYQANASQ
FT FRFGAGKSMEQRRETGNLIPIAQRSMGSTSTPFGSAPTQSYFGGGSSGAALSSPRKMQQ
FT THQMLFGNIQP -> MADDDDRVDISNETLASLVGRPMSSSGNRIRATPSRRRLVSAPT
FT NPRWSPSADDRRLFSYVSSMRSDSNSSSKSPSPPSAKMSKRPNGPYSVRKYQ (in
FT isoform a, isoform f and isoform g)"
FT /id="VSP_060892"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform d and isoform e)"
FT /id="VSP_060893"
FT VAR_SEQ 1..60
FT /note="MIRQLNSPGGGGGLGLNNPRAQQPPGAQQQQQPQQAQQQFYDDEPYQANASQ
FT FRFGAGKS -> MAASWLPNQ (in isoform i and isoform j)"
FT /id="VSP_060894"
FT VAR_SEQ 155..179
FT /note="Missing (in isoform b, isoform e, isoform f and
FT isoform j)"
FT /id="VSP_060895"
FT VAR_SEQ 443..463
FT /note="RTSSGTASWKLPGSNAFSDLM -> SEPISQSFHARGFLLEPICEF (in
FT isoform g)"
FT /id="VSP_060896"
FT VAR_SEQ 464..524
FT /note="Missing (in isoform g)"
FT /id="VSP_060897"
SQ SEQUENCE 524 AA; 56857 MW; 7F36E7A088BE1D18 CRC64;
MIRQLNSPGG GGGLGLNNPR AQQPPGAQQQ QQPQQAQQQF YDDEPYQANA SQFRFGAGKS
MEQRRETGNL IPIAQRSMGS TSTPFGSAPT QSYFGGGSSG AALSSPRKMQ QTHQMLFGNI
QPPRGSPPSD GSDKIHRFGE SPTPGGVGGV FGTELDDLII DELMGMEDDQ RMRPGATRPM
TIGGEKTMSM ARPIPGASSR AGSGHSGSPI TIPNAMSNNF RQVVSSSAPT SSIDIEKMIG
AVSNGGGNSG GDNDPEDYYR DRRKKDIHNM IERRRRYNIN DRIKELGQML PKNTSEDMKL
NKGTILKASC DYIRVLQKDR EQAMKTQQQQ KSLESTAHKY ADRVKELEEM LARQGVQVPP
SHLPPIPKVI ERPIKQEIDE SPPNHTPTGS FVSSSGFLSE VTNNTAAMQI TSPNDSRPNN
FMNNSAPSDS FFSVGSASPP DYRTSSGTAS WKLPGSNAFS DLMMDDLNPM MNGDPLISSA
GAHPSPHFHS SQMSPDIHWD ASGFSPDPIN TQQSNSGHYH MDFS
