Q9V9Y4 · PHCL2_DROME

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).

Miscellaneous

The name 'hodor' is an acronym for 'hold on, don't rush', referring to the developmental delay phenotype in mutants.

Catalytic activity

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbrush border membrane
Cellular Componentchloride channel complex
Cellular Componentlate endosome membrane
Cellular Componentlysosomal membrane
Cellular Componentmicrovillus membrane
Cellular Componentneuron projection
Cellular Componentplasma membrane
Cellular Componentpostsynapse
Cellular Componentsynapse
Cellular Componenttransmembrane transporter complex
Molecular Functionchloride channel activity
Molecular Functionexcitatory extracellular ligand-gated monoatomic ion channel activity
Molecular Functionneurotransmitter receptor activity
Molecular FunctionpH-gated chloride channel activity
Molecular Functiontransmembrane signaling receptor activity
Molecular Functionzinc ion sensor activity
Biological Processcellular response to zinc ion
Biological Processchloride transmembrane transport
Biological Processpositive regulation of insulin-like growth factor receptor signaling pathway
Biological Processpositive regulation of TORC1 signaling
Biological Processregulation of renal water transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    pH-sensitive chloride channel 2
  • Alternative names
    • Ligand-gated chloride channel protein hodor

Gene names

    • Name
      pHCl-2
    • Synonyms
      hodor
    • ORF names
      CG11340

Organism names

  • Taxonomic identifier
  • Strain
    • Berkeley
  • Taxonomic lineage
    Eukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora

Accessions

  • Primary accession
    Q9V9Y4
  • Secondary accessions
    • E3CTP9

Proteomes

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain19-300Extracellular
Transmembrane301-321Helical; Name=1
Topological domain322-327Cytoplasmic
Transmembrane328-347Helical; Name=2
Topological domain348-360Extracellular
Transmembrane361-381Helical; Name=3
Topological domain382-505Cytoplasmic
Transmembrane506-526Helical; Name=4

Keywords

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis255Results in zinc-elicited currents with increased rise time and deactivation kinetics in Xenopus oocytes; when associated with F-296.
Mutagenesis296Results in zinc-elicited currents with increased rise time and deactivation kinetics in Xenopus oocytes; when associated with K-255.

PTM/Processing

Features

Showing features for signal, chain, glycosylation.

TypeIDPosition(s)Description
Signal1-18
ChainPRO_501510003019-526pH-sensitive chloride channel 2
Glycosylation33N-linked (GlcNAc...) asparagine
Glycosylation42N-linked (GlcNAc...) asparagine
Glycosylation52N-linked (GlcNAc...) asparagine
Glycosylation192N-linked (GlcNAc...) asparagine
Glycosylation231N-linked (GlcNAc...) asparagine
Glycosylation264N-linked (GlcNAc...) asparagine
Glycosylation271N-linked (GlcNAc...) asparagine
Glycosylation283N-linked (GlcNAc...) asparagine

Keywords

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).

Gene expression databases

    • FBgn0039840Expressed in adult Malpighian tubule (Drosophila) and 9 other cell types or tissues

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region463-488Disordered

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    526
  • Mass (Da)
    59,826
  • Last updated
    2000-05-01 v1
  • Checksum
    BC78EC5EC219F596
MDTLGIFVLISYLGLSSAAGVHLGDLQQNLAANGSVVVSPLNTTDAFSVSINLSQSTVNNCPSLKNAESMALMELLTRLTAPCRYDRMVPPVVHNKDGEEVPMDIYARFYIYVMKNLDSSDLQFTVQGLLQLRYLDPRLAFSSYLPNRRQPIMGESELKKMLWVPHIFLTNEQASTVLGTSAKDELTSIYPNGTVLTSTRLQATLYCWMNFQKFPFDEQKCKTTLESWMYNTTLVQLHWETDNPVSFDKQLQLTEYNLIGSLYNESIRVSNESYMSHGSLEGNYSIISFTVLLTREVGYYVIDYFLPSIMIVTISWVSFWLQADQTPARTTLGCTTLLSFITLSLSQENNLMKVSYVTMSEVWFLVCTIFIFGSLVEFAFVNTIWRRNNDLQLKKRTTKYIVKSTFVPHLKKHRRHGYRRTDSTMSTMSTTSMDKTCGPNNTVITIETPIIIGGSLSREDSAISLDEQDETSTSESSDSSKEKPAQTFATMTPKEVSLWIDRKMRFVFPLSFIVFNALFWTLVYCL

Sequence caution

The sequence ADO51077.1 differs from that shown. Reason: Miscellaneous discrepancy Probable cloning artifact.

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict299in Ref. 3; ADO51077

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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.

Genome annotation databases

Similar Proteins

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