D3Z291 · CAHM1_MOUSE
- ProteinCalcium homeostasis modulator protein 1
- GeneCalhm1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids348 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes (PubMed:23467090).
With CALHM3 forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (PubMed:23467090, PubMed:29681531).
Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to membrane depolarization and low extracellular Ca2+ concentration. Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of small ions including Ca2+, Na+, K+ and Cl-, as well as larger ions such as ATP4- (PubMed:22711817, PubMed:28734079, PubMed:29681531, PubMed:33788965).
Mediates Ca2+ influx and downstream activation of the ERK1 and ERK2 cascade in neurons (By similarity).
Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (By similarity).
May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca2+ dependent manner (By similarity).
With CALHM3 forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (PubMed:23467090, PubMed:29681531).
Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to membrane depolarization and low extracellular Ca2+ concentration. Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of small ions including Ca2+, Na+, K+ and Cl-, as well as larger ions such as ATP4- (PubMed:22711817, PubMed:28734079, PubMed:29681531, PubMed:33788965).
Mediates Ca2+ influx and downstream activation of the ERK1 and ERK2 cascade in neurons (By similarity).
Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (By similarity).
May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca2+ dependent manner (By similarity).
Catalytic activity
- ATP(in) = ATP(out)
- Ca2+(in) = Ca2+(out)
- Mg2+(in) = Mg2+(out)
- Na+(in) = Na+(out)
- K+(in) = K+(out)
- Li+(in) = Li+(out)
- Rb+(in) = Rb+(out)
- Cs+(in) = Cs+(out)
- chloride(in) = chloride(out)
Activity regulation
Regulated by membrane voltage and extracellular Ca2+. Inhibited by Gd3+, ruthenium red, and Zn2+ and partially inhibited by 2-aminoethoxydiphenyl borate.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | basolateral plasma membrane | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane raft | |
Molecular Function | calcium-activated cation channel activity | |
Molecular Function | identical protein binding | |
Molecular Function | monoatomic cation channel activity | |
Molecular Function | voltage-gated calcium channel activity | |
Molecular Function | voltage-gated channel activity | |
Molecular Function | voltage-gated monoatomic ion channel activity | |
Biological Process | ATP export | |
Biological Process | ATP transport | |
Biological Process | monoatomic cation transport | |
Biological Process | protein heterooligomerization | |
Biological Process | protein homooligomerization | |
Biological Process | regulation of monoatomic ion transmembrane transport | |
Biological Process | sensory perception of bitter taste | |
Biological Process | sensory perception of sweet taste | |
Biological Process | sensory perception of taste | |
Biological Process | sensory perception of umami taste |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameCalcium homeostasis modulator protein 1
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionD3Z291
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Note: Localizes to the basolateral membrane of epithelial cells including taste cells (PubMed:30804437).
Colocalizes with HSPA5 at the endoplasmic reticulum (By similarity).
Colocalizes with HSPA5 at the endoplasmic reticulum (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-20 | Cytoplasmic | ||||
Sequence: MDKFRMIFQFLQSNQESFMN | ||||||
Transmembrane | 21-36 | Helical; Name=S1 | ||||
Sequence: GICGIMALASAQMYSA | ||||||
Topological domain | 37-48 | Extracellular | ||||
Sequence: FDFNCPCLPGYN | ||||||
Transmembrane | 49-71 | Helical; Name=S2 | ||||
Sequence: VVYSLGILLTPPLVLFLLGLVMN | ||||||
Topological domain | 72-98 | Cytoplasmic | ||||
Sequence: NNISMLAEEWKRPAGRRAKDPAVLRYM | ||||||
Transmembrane | 99-124 | Helical; Name=S3 | ||||
Sequence: FCSMAQRALIAPVVWVAVTLLDGKCF | ||||||
Topological domain | 125-179 | Extracellular | ||||
Sequence: LCAFCTAVPVATLGNGSLVPGLPAPELARLLARVPCPEIYDGNWLLAREVAVRYL | ||||||
Transmembrane | 180-205 | Helical; Name=S4 | ||||
Sequence: RCISQALGWSFVLLTTLLAFVVRSVR | ||||||
Topological domain | 206-348 | Cytoplasmic | ||||
Sequence: PCFTQVAFLKSKYWSHYIDIERKLFDETCTEHAKAFAKVCIQQFFEAMNHDLELGHTHGVLATATATATATEAVQSPSDRTEEEREKLRGITDQGTMNRLLTSWHKCKPPLRLGQEAPLMSNGWAGGEPRPPRKEVATYFSKV |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Impaired perceptions of sweet, bitter and umami compounds. Mice are viable and fertile, with no visible morphological abnormalities in their taste buds or any altered expression of taste-related marker genes. They do however display a loss of both preference for sweet and umami compounds and for avoidance of bitter compounds. Perceptions of sour and salty tastes are unaffected. Reduced voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Elderly males and females do not show defects in spatial learning and memory retrieving.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 23 | Increases channel trafficking to the plasma membrane and ATP release. | ||||
Sequence: C → S | ||||||
Mutagenesis | 76-77 | Affects basolateral membrane sorting in vitro but not in vivo; when associated with A-222 and A-225. | ||||
Sequence: ML → AA | ||||||
Mutagenesis | 100 | Decreases palmitoylation and only slightly increases channel activity. Has no significant effect on channel trafficking to the plasma membrane. Loss of palmitoylation, gain-of-function and high cytotoxicity; when associated with S-207. | ||||
Sequence: C → S | ||||||
Mutagenesis | 123 | Decreases channel trafficking to the plasma membrane. Abolishes ATP release. | ||||
Sequence: C → S | ||||||
Mutagenesis | 126 | Decreases channel trafficking to the plasma membrane. Abolishes ATP release. | ||||
Sequence: C → S | ||||||
Mutagenesis | 139 | Loss of N-glycosylation associated with enhanced proteosomal degradation and impaired channel trafficking to plasma membrane. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 207 | Has no significant effect on ATP release or channel trafficking to the plasma membrane. Loss of palmitoylation, gain-of-function and high cytotoxicity; when associated with S-100. | ||||
Sequence: C → S | ||||||
Mutagenesis | 222 | Affects basolateral membrane sorting in vitro but not in vivo; when associated with 76-A-A-77 and A-225. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 225 | Affects basolateral membrane sorting in vitro but not in vivo; when associated with 76-A-A-77 and A-222. | ||||
Sequence: I → A | ||||||
Mutagenesis | 234 | Decreases ATP release. Does not affect channel trafficking to the plasma membrane. | ||||
Sequence: C → S | ||||||
Mutagenesis | 245 | Increases channel trafficking to the plasma membrane. Decreases ATP release. | ||||
Sequence: C → S | ||||||
Mutagenesis | 312 | Decreases ATP release. Does not affect channel trafficking to the plasma membrane. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, disulfide bond, lipidation, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000422239 | 1-348 | Calcium homeostasis modulator protein 1 | |||
Sequence: MDKFRMIFQFLQSNQESFMNGICGIMALASAQMYSAFDFNCPCLPGYNVVYSLGILLTPPLVLFLLGLVMNNNISMLAEEWKRPAGRRAKDPAVLRYMFCSMAQRALIAPVVWVAVTLLDGKCFLCAFCTAVPVATLGNGSLVPGLPAPELARLLARVPCPEIYDGNWLLAREVAVRYLRCISQALGWSFVLLTTLLAFVVRSVRPCFTQVAFLKSKYWSHYIDIERKLFDETCTEHAKAFAKVCIQQFFEAMNHDLELGHTHGVLATATATATATEAVQSPSDRTEEEREKLRGITDQGTMNRLLTSWHKCKPPLRLGQEAPLMSNGWAGGEPRPPRKEVATYFSKV | ||||||
Disulfide bond | 41↔126 | |||||
Sequence: CPCLPGYNVVYSLGILLTPPLVLFLLGLVMNNNISMLAEEWKRPAGRRAKDPAVLRYMFCSMAQRALIAPVVWVAVTLLDGKCFLC | ||||||
Disulfide bond | 43↔160 | |||||
Sequence: CLPGYNVVYSLGILLTPPLVLFLLGLVMNNNISMLAEEWKRPAGRRAKDPAVLRYMFCSMAQRALIAPVVWVAVTLLDGKCFLCAFCTAVPVATLGNGSLVPGLPAPELARLLARVPC | ||||||
Lipidation | 100 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Glycosylation | 139 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Lipidation | 207 | S-palmitoyl cysteine | ||||
Sequence: C |
Post-translational modification
N-glycosylated. Assembly with CALHM3 is associated with N-glycan remodeling and formation of hybrid complex- and high mannose-type glycochains. This N-glycan processing regulates channel trafficking and gating kinetics.
Palmitoylated by ZDHHC3, ZDHHC20 and possibly ZDHHC7. Palmitoylation regulates voltage-dependent gating of the channel by shifting it toward more depolarized potentials.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Specifically expressed in type II taste bud cells (at protein level). Not expressed in brain.
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 9-36 | Central pore | ||||
Sequence: QFLQSNQESFMNGICGIMALASAQMYSA | ||||||
Region | 62-69 | Phospholipid-binding | ||||
Sequence: VLFLLGLV | ||||||
Region | 104-116 | Phospholipid-binding | ||||
Sequence: QRALIAPVVWVAV | ||||||
Region | 191-201 | Phospholipid-binding | ||||
Sequence: VLLTTLLAFVV | ||||||
Region | 324-348 | Disordered | ||||
Sequence: LMSNGWAGGEPRPPRKEVATYFSKV |
Domain
A phospholipid-binding pocket is formed between conserved regions of S3 and S4 helices of one subunit and S2 of the adjacent subunit. It may regulate channel assembly and gating.
Sequence similarities
Belongs to the CALHM family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length348
- Mass (Da)38,827
- Last updated2010-04-20 v1
- Checksum338717B7C1F8C354
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC124724 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH466534 EMBL· GenBank· DDBJ | EDL42030.1 EMBL· GenBank· DDBJ | Genomic DNA |