Q9V9Y4 · PHCL2_DROME
- ProteinpH-sensitive chloride channel 2
- GenepHCl-2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids526 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Ligand and pH-gated channel that mediates chloride transport primarily in the mid-gut and thereby functions in larval metabolism and fluid homeostasis (PubMed:27172217, PubMed:27358471, PubMed:32269334).
Channel opening is triggered by zinc binding or, to a lesser extent, an increase in extracellular pH (PubMed:27358471, PubMed:32269334).
Zinc-dependent activity in the mid-gut is required for modulating Tor-dependent metabolic programs that promote larval feeding and systematic growth (PubMed:32269334).
It may therefore act as an intestinal zinc sensor that mediates larval growth and metabolism in response to micronutrient availability (PubMed:32269334).
Activates Tor signaling via its activity in maintaining lysosome homeostasis in interstitial cells and/or by its role in activating the release of insulin-like peptides in the brain after feeding, via an unknown mechanism (PubMed:32269334).
Functions in lysosome homeostasis by regulating chloride transport into enterocyte lysosomes to sustain V-ATPase function which maintains lysosomal acidification and consequently promotes Tor activation at the lysosome membrane (PubMed:32269334).
Also appears to play a role in regulating fluid secretion and osmotic homeostasis in Malpighian tubules in response to the pH of extracellular urine (PubMed:27358471).
This function is important for proper urine production during diuresis (PubMed:27358471).
Channel opening is triggered by zinc binding or, to a lesser extent, an increase in extracellular pH (PubMed:27358471, PubMed:32269334).
Zinc-dependent activity in the mid-gut is required for modulating Tor-dependent metabolic programs that promote larval feeding and systematic growth (PubMed:32269334).
It may therefore act as an intestinal zinc sensor that mediates larval growth and metabolism in response to micronutrient availability (PubMed:32269334).
Activates Tor signaling via its activity in maintaining lysosome homeostasis in interstitial cells and/or by its role in activating the release of insulin-like peptides in the brain after feeding, via an unknown mechanism (PubMed:32269334).
Functions in lysosome homeostasis by regulating chloride transport into enterocyte lysosomes to sustain V-ATPase function which maintains lysosomal acidification and consequently promotes Tor activation at the lysosome membrane (PubMed:32269334).
Also appears to play a role in regulating fluid secretion and osmotic homeostasis in Malpighian tubules in response to the pH of extracellular urine (PubMed:27358471).
This function is important for proper urine production during diuresis (PubMed:27358471).
Miscellaneous
The name 'hodor' is an acronym for 'hold on, don't rush', referring to the developmental delay phenotype in mutants.
Catalytic activity
- chloride(in) = chloride(out)This reaction proceeds in the forward direction.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namepH-sensitive chloride channel 2
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionQ9V9Y4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Cell projection, microvillus membrane ; Multi-pass membrane protein
Late endosome membrane ; Multi-pass membrane protein
Lysosome membrane ; Multi-pass membrane protein
Note: Enriched on the apical side of gut interstitial cells; on the brush-border and on the lysosomes.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 19-300 | Extracellular | ||||
Sequence: AGVHLGDLQQNLAANGSVVVSPLNTTDAFSVSINLSQSTVNNCPSLKNAESMALMELLTRLTAPCRYDRMVPPVVHNKDGEEVPMDIYARFYIYVMKNLDSSDLQFTVQGLLQLRYLDPRLAFSSYLPNRRQPIMGESELKKMLWVPHIFLTNEQASTVLGTSAKDELTSIYPNGTVLTSTRLQATLYCWMNFQKFPFDEQKCKTTLESWMYNTTLVQLHWETDNPVSFDKQLQLTEYNLIGSLYNESIRVSNESYMSHGSLEGNYSIISFTVLLTREVGYY | ||||||
Transmembrane | 301-321 | Helical; Name=1 | ||||
Sequence: VIDYFLPSIMIVTISWVSFWL | ||||||
Topological domain | 322-327 | Cytoplasmic | ||||
Sequence: QADQTP | ||||||
Transmembrane | 328-347 | Helical; Name=2 | ||||
Sequence: ARTTLGCTTLLSFITLSLSQ | ||||||
Topological domain | 348-360 | Extracellular | ||||
Sequence: ENNLMKVSYVTMS | ||||||
Transmembrane | 361-381 | Helical; Name=3 | ||||
Sequence: EVWFLVCTIFIFGSLVEFAFV | ||||||
Topological domain | 382-505 | Cytoplasmic | ||||
Sequence: NTIWRRNNDLQLKKRTTKYIVKSTFVPHLKKHRRHGYRRTDSTMSTMSTTSMDKTCGPNNTVITIETPIIIGGSLSREDSAISLDEQDETSTSESSDSSKEKPAQTFATMTPKEVSLWIDRKMR | ||||||
Transmembrane | 506-526 | Helical; Name=4 | ||||
Sequence: FVFPLSFIVFNALFWTLVYCL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Larval lethal (PubMed:32269334).
Larval development is delayed due to decreased food intake and reduced systematic insulin signaling (PubMed:32269334).
However, escapers eventually attain a normal size during the pupal and adult stages (PubMed:32269334).
Unlike in wild-type larvae, mutants do not develop a preference for zinc supplemented food or eat more when fed a zinc rich diet (PubMed:32269334).
The copper cell region of the larval midgut displays developmental and functional defects such as reduced luminal acidity, increased bacterial titers and enlarged cell volume (PubMed:32269334).
The interstitial cells also display increased cell volume due to reduced basal infolding (PubMed:32269334).
They also display an increased tolerance to copper but not zinc, likely due to increased cell acidity which has been found to decrease copper uptake (PubMed:27172217).
Postembryonic knockdown specifically in interstitial and Malpighian tubule principal cells also results in reduced food intake and increased time to pupation, whereas knockdown only in principal cells, iron cells or copper cells has no effect on larval development (PubMed:32269334).
Mutants display a further increase in developmental delay in a Tor RNAi-mediated background (PubMed:32269334).
Larval development is delayed due to decreased food intake and reduced systematic insulin signaling (PubMed:32269334).
However, escapers eventually attain a normal size during the pupal and adult stages (PubMed:32269334).
Unlike in wild-type larvae, mutants do not develop a preference for zinc supplemented food or eat more when fed a zinc rich diet (PubMed:32269334).
The copper cell region of the larval midgut displays developmental and functional defects such as reduced luminal acidity, increased bacterial titers and enlarged cell volume (PubMed:32269334).
The interstitial cells also display increased cell volume due to reduced basal infolding (PubMed:32269334).
They also display an increased tolerance to copper but not zinc, likely due to increased cell acidity which has been found to decrease copper uptake (PubMed:27172217).
Postembryonic knockdown specifically in interstitial and Malpighian tubule principal cells also results in reduced food intake and increased time to pupation, whereas knockdown only in principal cells, iron cells or copper cells has no effect on larval development (PubMed:32269334).
Mutants display a further increase in developmental delay in a Tor RNAi-mediated background (PubMed:32269334).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 255 | Results in zinc-elicited currents with increased rise time and deactivation kinetics in Xenopus oocytes; when associated with F-296. | ||||
Sequence: E → K | ||||||
Mutagenesis | 296 | Results in zinc-elicited currents with increased rise time and deactivation kinetics in Xenopus oocytes; when associated with K-255. | ||||
Sequence: E → F |
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-18 | |||||
Sequence: MDTLGIFVLISYLGLSSA | ||||||
Chain | PRO_5015100030 | 19-526 | pH-sensitive chloride channel 2 | |||
Sequence: AGVHLGDLQQNLAANGSVVVSPLNTTDAFSVSINLSQSTVNNCPSLKNAESMALMELLTRLTAPCRYDRMVPPVVHNKDGEEVPMDIYARFYIYVMKNLDSSDLQFTVQGLLQLRYLDPRLAFSSYLPNRRQPIMGESELKKMLWVPHIFLTNEQASTVLGTSAKDELTSIYPNGTVLTSTRLQATLYCWMNFQKFPFDEQKCKTTLESWMYNTTLVQLHWETDNPVSFDKQLQLTEYNLIGSLYNESIRVSNESYMSHGSLEGNYSIISFTVLLTREVGYYVIDYFLPSIMIVTISWVSFWLQADQTPARTTLGCTTLLSFITLSLSQENNLMKVSYVTMSEVWFLVCTIFIFGSLVEFAFVNTIWRRNNDLQLKKRTTKYIVKSTFVPHLKKHRRHGYRRTDSTMSTMSTTSMDKTCGPNNTVITIETPIIIGGSLSREDSAISLDEQDETSTSESSDSSKEKPAQTFATMTPKEVSLWIDRKMRFVFPLSFIVFNALFWTLVYCL | ||||||
Glycosylation | 33 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 42 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 52 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 192 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 231 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 264 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 271 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 283 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
In third-instar larvae, expressed in the principal cells of the excretory Malpighian tubules (at protein level) (PubMed:27358471, PubMed:32269334).
Also detected in the enterocytes of the copper cell region and the iron cell region of the larval midgut (at protein level) (PubMed:32269334).
In the copper cell region expression is confined to the interstitial cells and in the iron cell region it is expressed in the anterior portion (at protein level) (PubMed:32269334).
Expressed in the Malpighian tubules and the middle midgut of third instar larvae and adults (PubMed:27172217).
Also detected in the enterocytes of the copper cell region and the iron cell region of the larval midgut (at protein level) (PubMed:32269334).
In the copper cell region expression is confined to the interstitial cells and in the iron cell region it is expressed in the anterior portion (at protein level) (PubMed:32269334).
Expressed in the Malpighian tubules and the middle midgut of third instar larvae and adults (PubMed:27172217).
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 463-488 | Disordered | ||||
Sequence: ISLDEQDETSTSESSDSSKEKPAQTF |
Sequence similarities
Belongs to the ligand-gated ion channel (TC 1.A.9) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length526
- Mass (Da)59,826
- Last updated2000-05-01 v1
- ChecksumBC78EC5EC219F596
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 299 | in Ref. 3; ADO51077 | ||||
Sequence: Y → H |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE014297 EMBL· GenBank· DDBJ | AAF57144.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014297 EMBL· GenBank· DDBJ | ALI30655.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT125715 EMBL· GenBank· DDBJ | ADO51077.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |