G5EEG9 · HLH2_CAEEL
- ProteinHelix-loop-helix protein hlh-2
- Genehlh-2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids399 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcription factor which binds the E box motif 5'-CA[TC][AG]TG-3' (PubMed:11076762, PubMed:14701877, PubMed:19632181).
Plays a key role in the anchor cell/ventral uterine precursor cell (AC/VU) decision; required for VU fate (PubMed:14701877, PubMed:31402303).
Regulates expression of lin-12/Notch receptor and putative ligand lag-2 in the presumptive AC and presumptive VU cells (PubMed:31402303).
Modulates expression of lag-2 in the gonadal distal tip cells (DTCs) (PubMed:14701877, PubMed:19376107).
Involved in formation of the polarised cell membrane of the AC and thus facilitates invasion across the gonadal basement membrane, acting via transcriptional modulation of multiple genes (PubMed:21784067).
Involved in specification of the hermaphrodite DTC and the male linker cell, perhaps acting in concert with the homeobox protein, ceh-22 (PubMed:19376107).
Plays a role in regulation of migration of DTCs and the modulation of expression of alpha integrin ina-1 and ADAMTS protease gon-1 (PubMed:17588558, PubMed:25982859).
Required for DTC maintenance, and for function of the DTC as a niche for germline stem cells (PubMed:19376107).
Plays a role in cell-autonomously establishing a neuronal left-right asymmetry (PubMed:21041366).
Required for specification of cell fate, acting in concert with lin-32, in the development of the male-specific genital sensilla (simple sense organs) known as rays (PubMed:11076762).
Negatively modulates lifespan, perhaps acting by regulating expression of arginine kinases, which in turn results in altered metabolism and homeostasis of reactive oxygen species (ROS) (PubMed:32203922).
Plays a key role in the anchor cell/ventral uterine precursor cell (AC/VU) decision; required for VU fate (PubMed:14701877, PubMed:31402303).
Regulates expression of lin-12/Notch receptor and putative ligand lag-2 in the presumptive AC and presumptive VU cells (PubMed:31402303).
Modulates expression of lag-2 in the gonadal distal tip cells (DTCs) (PubMed:14701877, PubMed:19376107).
Involved in formation of the polarised cell membrane of the AC and thus facilitates invasion across the gonadal basement membrane, acting via transcriptional modulation of multiple genes (PubMed:21784067).
Involved in specification of the hermaphrodite DTC and the male linker cell, perhaps acting in concert with the homeobox protein, ceh-22 (PubMed:19376107).
Plays a role in regulation of migration of DTCs and the modulation of expression of alpha integrin ina-1 and ADAMTS protease gon-1 (PubMed:17588558, PubMed:25982859).
Required for DTC maintenance, and for function of the DTC as a niche for germline stem cells (PubMed:19376107).
Plays a role in cell-autonomously establishing a neuronal left-right asymmetry (PubMed:21041366).
Required for specification of cell fate, acting in concert with lin-32, in the development of the male-specific genital sensilla (simple sense organs) known as rays (PubMed:11076762).
Negatively modulates lifespan, perhaps acting by regulating expression of arginine kinases, which in turn results in altered metabolism and homeostasis of reactive oxygen species (ROS) (PubMed:32203922).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHelix-loop-helix protein hlh-2
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionG5EEG9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
RNAi-mediated knockdown in the early larval L1 stage causes both somatic gonadal progenitor (SGP) cells, Z1.ppp and Z4.aaa, to assume the ventral uterine precursor cell (VU) identity; whereas, if RNAi is applied during the late larval L1 stage, or at the larval L2 stage, both assume the anchor cell (AC) identity (PubMed:14701877, PubMed:21784067).
RNAi-mediated knockdown applied at the time of the larval stage L1/L2 molt causes defects in invasion of the basement membrane by the AC (PubMed:21784067).
RNAi-mediated knockdown causes the MI pharyngeal motorneuron to transform into an e3D-like epithelial cell (PubMed:21041366).
RNAi-mediated knockdown reduces expression of alpha integrin ina-1 and of ADAMTS protease gon-1, and causes defects in migration of the gonadal distal tip cells (DTCs) (PubMed:17588558, PubMed:25982859).
RNAi-mediated knockdown causes reduction in the number of hermaphrodites with DTCs, diminishes formation of elongated gonadal arms and reduces expression of lag-2 (PubMed:19376107).
RNAi-mediated knockdown during larval stage L3 causes a subsequent three-fold reduction in germ cell number in the adult hermaphrodite gonad (PubMed:19376107).
RNAi-mediated knockdown increases lifespan, reduces fertility, improves the response to proteotoxic stress, alters the response to reactive oxygen species (ROS) and reduces expression of arginine kinases such as argk-1 (PubMed:32203922).
RNAi-mediated knockdown applied at the time of the larval stage L1/L2 molt causes defects in invasion of the basement membrane by the AC (PubMed:21784067).
RNAi-mediated knockdown causes the MI pharyngeal motorneuron to transform into an e3D-like epithelial cell (PubMed:21041366).
RNAi-mediated knockdown reduces expression of alpha integrin ina-1 and of ADAMTS protease gon-1, and causes defects in migration of the gonadal distal tip cells (DTCs) (PubMed:17588558, PubMed:25982859).
RNAi-mediated knockdown causes reduction in the number of hermaphrodites with DTCs, diminishes formation of elongated gonadal arms and reduces expression of lag-2 (PubMed:19376107).
RNAi-mediated knockdown during larval stage L3 causes a subsequent three-fold reduction in germ cell number in the adult hermaphrodite gonad (PubMed:19376107).
RNAi-mediated knockdown increases lifespan, reduces fertility, improves the response to proteotoxic stress, alters the response to reactive oxygen species (ROS) and reduces expression of arginine kinases such as argk-1 (PubMed:32203922).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 316 | In bx108; enhances the loss of male-specific genital sensilla (simple sense organs) known as rays, on a lin-32 mutant background. Slightly reduces binding to DNA as a heterodimer with lin-32. | ||||
Sequence: R → H | ||||||
Mutagenesis | 352 | In bx115; enhances the loss of male-specific genital sensilla (simple sense organs) known as rays, on a lin-32 mutant background. Causes defects in all three ray cell types. Slightly reduces binding to DNA as a heterodimer with lin-32. | ||||
Sequence: V → M |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000453281 | 1-399 | Helix-loop-helix protein hlh-2 | |||
Sequence: MADPNSQLTSATTVATAAIAQPQVMLPNAYDYPYNIDPTTIQMPDYWSGYHLNPYPPMQTTDIDYSSAFLPTHPPTETPASVAAPTSATSDIKPIHATSSTSTTAPSTAPAPTSTTDVLELKPTTAPATNSAETSAIVAPQPLTNLTAPIDAMSSMYTWPQTYPGYLPPSEDNKASEAVNPYISIPPTYTFGADPSVADFSSYQQQLAGQPNGLGGDTNLVDYNHQFPPAGMSPHFDPNGYPGMTGMPPGSSASSVRNDKSASRATSRRRVQGPPSSGIPTRHSSSSRLSDNESMSDDKDTDRRSQNNARERVRVRDINSAFKELGRMCTQHNQNTERNQTKLGILHNAVSVITQLEEQVRQRNMNPKVMAGMKRKPDDDKMKMLDDNAPSAQFGHPRF |
Proteomic databases
Expression
Developmental stage
During male tail development, expressed in each of the nine Rn cells and in the anterior daughter cell, the ray neuroblast (at protein level) (PubMed:11076762).
First expressed at the comma stage of embryogenesis (PubMed:19632181).
Expressed asymmetrically, in the mother cell of the MI pharyngeal motorneuron but not in the mother cell of the e3D epithelial cell (PubMed:21041366).
Expressed during hermaphrodite gonadogenesis, in the two somatic gonadal progenitor (SGP) cells, Z1.ppp and Z4.aaa, precursors to the anchor cell (AC) and the ventral uterine precursor cell (VU), but not detected in their sister cells, Z1.ppa and Z4.aap (PubMed:14701877, PubMed:19376107, PubMed:21784067).
Expressed in both pre-AC and pre-VU cells, and after the AC/VU decision, expression is reduced in the VU and its descendants; however, expression persists in the AC through the time of basement membrane invasion (PubMed:21784067, PubMed:31402303).
Expressed in the gonadal distal tip cells (DTCs) throughout development and in adults (PubMed:19376107).
First expressed at the comma stage of embryogenesis (PubMed:19632181).
Expressed asymmetrically, in the mother cell of the MI pharyngeal motorneuron but not in the mother cell of the e3D epithelial cell (PubMed:21041366).
Expressed during hermaphrodite gonadogenesis, in the two somatic gonadal progenitor (SGP) cells, Z1.ppp and Z4.aaa, precursors to the anchor cell (AC) and the ventral uterine precursor cell (VU), but not detected in their sister cells, Z1.ppa and Z4.aap (PubMed:14701877, PubMed:19376107, PubMed:21784067).
Expressed in both pre-AC and pre-VU cells, and after the AC/VU decision, expression is reduced in the VU and its descendants; however, expression persists in the AC through the time of basement membrane invasion (PubMed:21784067, PubMed:31402303).
Expressed in the gonadal distal tip cells (DTCs) throughout development and in adults (PubMed:19376107).
Gene expression databases
Interaction
Subunit
Interacts with helix-loop-helix protein ngn-1; the interaction is direct (PubMed:21041366).
Efficient DNA binding probably requires dimerization with another helix-loop-helix protein (PubMed:11076762, PubMed:19632181).
Forms a heterodimer with helix-loop-helix protein hlh-12 (PubMed:17588558).
Forms a heterodimer with lin-32 (PubMed:11076762).
May form a heterodimer with hlh-10 (PubMed:19632181).
Efficient DNA binding probably requires dimerization with another helix-loop-helix protein (PubMed:11076762, PubMed:19632181).
Forms a heterodimer with helix-loop-helix protein hlh-12 (PubMed:17588558).
Forms a heterodimer with lin-32 (PubMed:11076762).
May form a heterodimer with hlh-10 (PubMed:19632181).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 66-119 | Disordered | ||||
Sequence: SSAFLPTHPPTETPASVAAPTSATSDIKPIHATSSTSTTAPSTAPAPTSTTDVL | ||||||
Region | 208-315 | Disordered | ||||
Sequence: AGQPNGLGGDTNLVDYNHQFPPAGMSPHFDPNGYPGMTGMPPGSSASSVRNDKSASRATSRRRVQGPPSSGIPTRHSSSSRLSDNESMSDDKDTDRRSQNNARERVRV | ||||||
Compositional bias | 248-291 | Polar residues | ||||
Sequence: PPGSSASSVRNDKSASRATSRRRVQGPPSSGIPTRHSSSSRLSD | ||||||
Compositional bias | 292-315 | Basic and acidic residues | ||||
Sequence: NESMSDDKDTDRRSQNNARERVRV | ||||||
Region | 302-315 | Basic motif | ||||
Sequence: DRRSQNNARERVRV | ||||||
Domain | 302-356 | bHLH | ||||
Sequence: DRRSQNNARERVRVRDINSAFKELGRMCTQHNQNTERNQTKLGILHNAVSVITQL | ||||||
Region | 316-356 | Helix-loop-helix motif | ||||
Sequence: RDINSAFKELGRMCTQHNQNTERNQTKLGILHNAVSVITQL | ||||||
Region | 371-399 | Disordered | ||||
Sequence: AGMKRKPDDDKMKMLDDNAPSAQFGHPRF | ||||||
Compositional bias | 372-386 | Basic and acidic residues | ||||
Sequence: GMKRKPDDDKMKMLD |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length399
- Mass (Da)43,193
- Last updated2011-12-14 v1
- Checksum8E139D03E597863B
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 210 | in Ref. 1; AAA21347/AAC13874 | ||||
Sequence: Q → P | ||||||
Sequence conflict | 224 | in Ref. 1; AAA21347/AAC13874 | ||||
Sequence: N → H | ||||||
Compositional bias | 248-291 | Polar residues | ||||
Sequence: PPGSSASSVRNDKSASRATSRRRVQGPPSSGIPTRHSSSSRLSD | ||||||
Compositional bias | 292-315 | Basic and acidic residues | ||||
Sequence: NESMSDDKDTDRRSQNNARERVRV | ||||||
Sequence conflict | 347 | in Ref. 1; AAA21347/AAC13874 | ||||
Sequence: H → Y | ||||||
Compositional bias | 372-386 | Basic and acidic residues | ||||
Sequence: GMKRKPDDDKMKMLD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U13614 EMBL· GenBank· DDBJ | AAA21347.1 EMBL· GenBank· DDBJ | mRNA | ||
U30248 EMBL· GenBank· DDBJ | AAC13874.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BX284601 EMBL· GenBank· DDBJ | CAA95837.1 EMBL· GenBank· DDBJ | Genomic DNA |