HLH3_CAEEL
ID HLH3_CAEEL Reviewed; 170 AA.
AC Q22717; P90977;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Helix-loop-helix protein 3 {ECO:0000305};
GN Name=hlh-3 {ECO:0000312|WormBase:T24B8.6};
GN ORFNames=T24B8.6 {ECO:0000312|WormBase:T24B8.6};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|EMBL:AAB38323.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yuan J., Greenwald I., Cole M.D.;
RT "hlh-3, a Caenorhabditis elegans achaete-scute like gene.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
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 INTERACTION WITH HLH-2, AND DEVELOPMENTAL STAGE.
RX PubMed=9187144; DOI=10.1242/dev.124.11.2179;
RA Krause M., Park M., Zhang J.M., Yuan J., Harfe B., Xu S.Q., Greenwald I.,
RA Cole M., Paterson B., Fire A.;
RT "A C. elegans E/Daughterless bHLH protein marks neuronal but not striated
RT muscle development.";
RL Development 124:2179-2189(1997).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HLH-2, AND DISRUPTION PHENOTYPE.
RX PubMed=12874127; DOI=10.1242/dev.00597;
RA Thellmann M., Hatzold J., Conradt B.;
RT "The Snail-like CES-1 protein of C. elegans can block the expression of the
RT BH3-only cell-death activator gene egl-1 by antagonizing the function of
RT bHLH proteins.";
RL Development 130:4057-4071(2003).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18586090; DOI=10.1016/j.mod.2008.06.002;
RA Doonan R., Hatzold J., Raut S., Conradt B., Alfonso A.;
RT "HLH-3 is a C. elegans Achaete/Scute protein required for differentiation
RT of the hermaphrodite-specific motor neurons.";
RL Mech. Dev. 125:883-893(2008).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 41-GLN--TYR-170.
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).
CC -!- FUNCTION: Probable transcriptional regulator (PubMed:12874127,
CC PubMed:18586090). May mediate transcriptional activation by binding to
CC the E-box motif 5'-CANNTG-3' (PubMed:9187144, PubMed:12874127). Plays a
CC role in the differentiation of the hermaphrodite-specific motor neurons
CC (HSN) that are required for normal egg laying (PubMed:18586090). Might
CC play a role in serotonin production by regulating expression of the
CC tryptophan hydrolase tph-1 which catalyzes serotonin synthesis, in the
CC HSN neurons (PubMed:18586090). Also plays a role in HSN axon guidance
CC towards the vulva and the ventral nerve cord, possibly by promoting the
CC expression of the netrin receptor unc-40 (PubMed:18586090). Under
CC feeding conditions, involved in the regulation of the srh-234
CC chemoreceptor encoding gene expression in the ADL sensory neurons
CC (PubMed:27487365). Together with hlh-2, involved in the induction of
CC programmed cell death in the sister cells of the serotonergic
CC neurosecretory motor (NSM) neurons, probably through the activation of
CC egl-1 transcription (PubMed:12874127). {ECO:0000269|PubMed:12874127,
CC ECO:0000269|PubMed:18586090, ECO:0000269|PubMed:27487365}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms a heterodimer with hlh-2. {ECO:0000269|PubMed:12874127,
CC ECO:0000269|PubMed:9187144}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:18586090}.
CC -!- TISSUE SPECIFICITY: Expressed in the ADL sensory neurons.
CC {ECO:0000269|PubMed:27487365}.
CC -!- DEVELOPMENTAL STAGE: Expressed in neuronal precursor cells during
CC embryogenesis (PubMed:9187144, PubMed:27487365). Expressed in nerve
CC ring ganglia neurons in very early larval stage L1, which is
CC undetectable by early larval stage L1 (PubMed:18586090). During L1,
CC expressed in the P cell lineage, specifically in the ectodermal-like P
CC cells, and expression persists in the primary and secondary neural
CC precursors of the P cell lineages (PubMed:18586090). Later, appears to
CC be expressed in all 53 of the resulting postmitotic motor neurons
CC during larval stage L1 (PubMed:18586090). Expression in most of these
CC neurons is undetectable by larval stage L2 (PubMed:18586090). Also
CC expressed in the hermaphrodite-specific motor neurons (HSN) and in the
CC ventral type C (VC) motor neurons throughout larval development
CC (PubMed:18586090). Expression in the HSNs persists until late L4 larval
CC stage (PubMed:18586090). {ECO:0000269|PubMed:18586090,
CC ECO:0000269|PubMed:27487365, ECO:0000269|PubMed:9187144}.
CC -!- DISRUPTION PHENOTYPE: Egg-laying defective (PubMed:18586090). Reduced
CC expression of the tryptophan hydroxylase tph-1 which leads to reduced
CC production of the neurotransmitter serotonin in the hermaphrodite-
CC specific motor neurons (HSN) (PubMed:18586090). Inappropriate lateral
CC projection of HSN axons (PubMed:18586090). Lack of netrin receptor unc-
CC 40 expression in a subset of HSN and VC motor neurons
CC (PubMed:18586090). RNAi-mediated knockdown prevents cell death of a
CC subset of the serotonergic neurosecretory motor (NSM) neuron sister
CC cells, and survival of NSM sister cells is increased in an hlh-2 mutant
CC background (PubMed:12874127). {ECO:0000269|PubMed:12874127,
CC ECO:0000269|PubMed:18586090}.
CC -!- CAUTION: Contains a degenerate basic motif not likely to bind DNA.
CC {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB38323.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U78953; AAB38323.1; ALT_FRAME; mRNA.
DR EMBL; BX284602; CAA92758.2; -; Genomic_DNA.
DR RefSeq; NP_495938.4; NM_063537.6.
DR AlphaFoldDB; Q22717; -.
DR SMR; Q22717; -.
DR IntAct; Q22717; 7.
DR STRING; 6239.T24B8.6; -.
DR PaxDb; Q22717; -.
DR EnsemblMetazoa; T24B8.6.1; T24B8.6.1; WBGene00001950.
DR GeneID; 174447; -.
DR KEGG; cel:CELE_T24B8.6; -.
DR UCSC; T24B8.6; c. elegans.
DR CTD; 174447; -.
DR WormBase; T24B8.6; CE42887; WBGene00001950; hlh-3.
DR eggNOG; KOG4029; Eukaryota.
DR HOGENOM; CLU_1572016_0_0_1; -.
DR InParanoid; Q22717; -.
DR OMA; YSHTETY; -.
DR OrthoDB; 1628647at2759; -.
DR PhylomeDB; Q22717; -.
DR SignaLink; Q22717; -.
DR PRO; PR:Q22717; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00001950; Expressed in embryo and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA: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; IMP:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030182; P:neuron differentiation; IMP:WormBase.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IMP:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0048841; P:regulation of axon extension involved in axon guidance; IMP:WormBase.
DR GO; GO:0046662; P:regulation of oviposition; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032094; P:response to food; IMP:UniProtKB.
DR GO; GO:0042427; P:serotonin biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR015660; MASH1/Ascl1a-like.
DR PANTHER; PTHR13935; PTHR13935; 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 Apoptosis; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Serotonin biosynthesis; Transcription;
KW Transcription regulation.
FT CHAIN 1..170
FT /note="Helix-loop-helix protein 3"
FT /id="PRO_0000439501"
FT DOMAIN 26..79
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..39
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 40..79
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 118..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..164
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 41..170
FT /note="Missing: In ot354; decreased expression of srh-234
FT in the cell body of ADL sensory neurons."
FT /evidence="ECO:0000269|PubMed:27487365"
SQ SEQUENCE 170 AA; 18944 MW; 62FDC3168DEB3C9B CRC64;
MTASTSSTPS TSTKIPSSSK SSVTKQTKQK RNERERKRVD QVNQGFVLLQ ERVPKAAGNK
AKLSKVETLR EAARYIQELQ KQLGMSSTSF HNSMPADFPT PEQSPVYPQS VCSMMAQTPS
PSYTSPYYPP PQMMSSNQHD MSSHYYQESS SSSASTSGDH HSFYSHTETY
