S5UH55 · TRPM5_DANRE
- ProteinTransient receptor potential cation channel subfamily M member 5
- Genetrpm5
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1165 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Monovalent cation-selective ion channel activated by intracellular Ca2+ in a voltage- and temperature-dependent manner. Mediates the transport of Na+, K+ and Cs+ ions equally well. Activated directly by increase in intracellular Ca2+, but is impermeable to it. The activation mechanism of TRPM5 involves a multistep process. TRPM5 activation involves ligand binding (i.e., tastant molecule, glucose stimulation) to Gq/G-protein coupled receptors (GPCR) and leads to the breakdown of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3), IP3 binds to its receptors in the endoplasmic reticulum and cause Ca2+ release. Simultaneously with the intracellular Ca2+ release, DAG activates the protein kinase C (PKC), which phosphorylates the TRPM5 channel. This phosphorylation combined with the bound Ca2+, leads to a robust inward current allowing the entry of sodium ions (Na+) into the cell. This ion influx depolarizes the cell membrane, generating action potentials that propagate TRPM5 signals.
Catalytic activity
- Na+(in) = Na+(out)
- K+(in) = K+(out)
Activity regulation
Ca2+-activated cation channel (PubMed:34168372).
Displays voltage dependence modulation (PubMed:34168372).
Regulated by PI(4,5)P2 levels. PI(4,5)P 2 reverses the Ca2+ -induced desensitization of channels. Is highly temperature-sensitive (By similarity).
Displays voltage dependence modulation (PubMed:34168372).
Regulated by PI(4,5)P2 levels. PI(4,5)P 2 reverses the Ca2+ -induced desensitization of channels. Is highly temperature-sensitive (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 212 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 324 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 333 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 336 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 337 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 768 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 771 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 794 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 797 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 994 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | plasma membrane | |
Molecular Function | calcium ion binding | |
Molecular Function | calcium-activated cation channel activity | |
Molecular Function | identical protein binding | |
Molecular Function | ligand-gated calcium channel activity | |
Biological Process | calcium ion transmembrane transport |
Keywords
- Molecular function
- Biological process
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTransient receptor potential cation channel subfamily M member 5
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio
Accessions
- Primary accessionS5UH55
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-715 | Cytoplasmic | ||||
Sequence: MVEKSSERFDKQMAGRLGDIDFTGVSRTRGKFVRVTSSTDPAEIYQILTKQWGLAPPHLVVALMGGDEVAQLKPWLRDTLRKGLVKAAQSTGAWILTSGLRFGITKNLGQAVRDHSLASTSPKVRVVAIGIAPWNMIQNRDLLLSAKPDHPATYPTEDLPYGAVYSLDCNHSHFILVDEDPKRPGATGEMRVKMLKHISLQRTGYGGTGSIEIPVLCLLVHGEPRILQKMYKNIQNSIPWLILAGSGGVADILVTLMDRGCWDADIVQELLINTFPDGLHSTEITSWTKLIQRILDHGHLLTVHDPEQDSELDTVILKALVKACKSQSQEAQDFLDELKLAVAWNRVDIAKSEIFSGDVQWSAQDLEEVMMEALVNDKPDFVRLFVDNGVNIKQFLTYGRLQELYCSVSEKNLLHTLLLKKNQERQAQLARKRMSGNPNNELGDRKFRFTFHEVSKVLKDFLDDTCKGFYQKLPAERMGKGRLFHSQKNLPDMDRRCEHPWRDLFLWAILQNRQEMANYFWAMGPEAVAAALVGCKIMKEMAHLATEAESARSMKNAKYEQFAMDLFSECYSNSEDRAYSLLVRKTCCWSKATVLNIATLAEAKCFFAHDGVQALLTKVWWGAMRTDTSISRLVLTFFIPPLVWTSLIKFNPEEQVSKDEGEPFAELDSLETEQALLLTDGDPVAGEGSAETAARSCSATFIRVVLRRWNRFWSA | ||||||
Transmembrane | 716-740 | Helical; Name=1 | ||||
Sequence: PVTVFMGNVIMYFAFLILFSYVLLL | ||||||
Topological domain | 741-751 | Extracellular | ||||
Sequence: DFRPPPPYGPS | ||||||
Transmembrane | 752-771 | Helical; Name=2 | ||||
Sequence: AAEIILYFWVFTLVLEEIRQ | ||||||
Topological domain | 772-792 | Cytoplasmic | ||||
Sequence: SFFTDEDMSILKKMKLYVEDN | ||||||
Transmembrane | 793-811 | Helical; Name=3 | ||||
Sequence: WNKCDMVAISLFVVGLSCR | ||||||
Topological domain | 812-818 | Extracellular | ||||
Sequence: MAMSTYE | ||||||
Transmembrane | 819-841 | Helical; Name=4 | ||||
Sequence: AGRTVLALDFMVFTLRLIHIFAI | ||||||
Topological domain | 842-850 | Cytoplasmic | ||||
Sequence: HKQLGPKII | ||||||
Transmembrane | 851-880 | Helical; Name=5 | ||||
Sequence: IVERMIKDVFFFLFFLSVWLIAYGVTTQAL | ||||||
Topological domain | 881-889 | Extracellular | ||||
Sequence: LHPNDPRID | ||||||
Intramembrane | 890-930 | Pore-forming | ||||
Sequence: WVFRRALYRPYLHIFGQIPLEEIDAAKMPDDNCTTDVQEII | ||||||
Topological domain | 931-942 | Extracellular | ||||
Sequence: LGTLPPCPNIYA | ||||||
Transmembrane | 943-977 | Helical; Name=6 | ||||
Sequence: NWLVILLLVIYLLVTNVLLLNLLIAMFSYTFQVVQ | ||||||
Topological domain | 978-1165 | Cytoplasmic | ||||
Sequence: ENADIFWKFQRYNLIVEYHSRPALAPPFIIISHITQALLSFIKKTENTQDLLERELPSGLDQKLMTWETVQKENYLAKLEHEHRESSGERLRYTSSKVQTLLRMVGGFKDQEKRMATVETEVRYCGEVLSWIAECFHKSTLKCDRDAPKAPRSIAGSSRDQQPQGAKRQQPAGHPAYGTDKKLPFIDH |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 337 | Altered the voltage sensitivity. Renders TRPM5 voltage-sensitive at high Ca2+ concentration. | ||||
Sequence: E → A | ||||||
Mutagenesis | 793 | The antagonist NDNA fails to suppress channel activity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 836 | The antagonist NDNA fails to suppress channel activity. | ||||
Sequence: I → A | ||||||
Mutagenesis | 853 | The antagonist NDNA fails to suppress channel activity. | ||||
Sequence: E → A |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000460930 | 1-1165 | Transient receptor potential cation channel subfamily M member 5 | |||
Sequence: MVEKSSERFDKQMAGRLGDIDFTGVSRTRGKFVRVTSSTDPAEIYQILTKQWGLAPPHLVVALMGGDEVAQLKPWLRDTLRKGLVKAAQSTGAWILTSGLRFGITKNLGQAVRDHSLASTSPKVRVVAIGIAPWNMIQNRDLLLSAKPDHPATYPTEDLPYGAVYSLDCNHSHFILVDEDPKRPGATGEMRVKMLKHISLQRTGYGGTGSIEIPVLCLLVHGEPRILQKMYKNIQNSIPWLILAGSGGVADILVTLMDRGCWDADIVQELLINTFPDGLHSTEITSWTKLIQRILDHGHLLTVHDPEQDSELDTVILKALVKACKSQSQEAQDFLDELKLAVAWNRVDIAKSEIFSGDVQWSAQDLEEVMMEALVNDKPDFVRLFVDNGVNIKQFLTYGRLQELYCSVSEKNLLHTLLLKKNQERQAQLARKRMSGNPNNELGDRKFRFTFHEVSKVLKDFLDDTCKGFYQKLPAERMGKGRLFHSQKNLPDMDRRCEHPWRDLFLWAILQNRQEMANYFWAMGPEAVAAALVGCKIMKEMAHLATEAESARSMKNAKYEQFAMDLFSECYSNSEDRAYSLLVRKTCCWSKATVLNIATLAEAKCFFAHDGVQALLTKVWWGAMRTDTSISRLVLTFFIPPLVWTSLIKFNPEEQVSKDEGEPFAELDSLETEQALLLTDGDPVAGEGSAETAARSCSATFIRVVLRRWNRFWSAPVTVFMGNVIMYFAFLILFSYVLLLDFRPPPPYGPSAAEIILYFWVFTLVLEEIRQSFFTDEDMSILKKMKLYVEDNWNKCDMVAISLFVVGLSCRMAMSTYEAGRTVLALDFMVFTLRLIHIFAIHKQLGPKIIIVERMIKDVFFFLFFLSVWLIAYGVTTQALLHPNDPRIDWVFRRALYRPYLHIFGQIPLEEIDAAKMPDDNCTTDVQEIILGTLPPCPNIYANWLVILLLVIYLLVTNVLLLNLLIAMFSYTFQVVQENADIFWKFQRYNLIVEYHSRPALAPPFIIISHITQALLSFIKKTENTQDLLERELPSGLDQKLMTWETVQKENYLAKLEHEHRESSGERLRYTSSKVQTLLRMVGGFKDQEKRMATVETEVRYCGEVLSWIAECFHKSTLKCDRDAPKAPRSIAGSSRDQQPQGAKRQQPAGHPAYGTDKKLPFIDH | ||||||
Modified residue | 121 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Expression
Gene expression databases
Interaction
Subunit
Homotetramer.
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 904-906 | Selectivity filter | ||||
Sequence: FGQ |
Domain
Contains two Ca2+-binding sites that are allosterically coupled. The binding site in the intracellular domain modulates the voltage dependence and the accessibility of Ca2+ in the transmembrane domain.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,165
- Mass (Da)132,655
- Last updated2024-10-02 v2
- Checksum835A4EABB94E5561
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8QPK7 | A0A2R8QPK7_DANRE | trpm5 | 1160 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 1149 | in Ref. 1; AGS55987 | ||||
Sequence: A → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KF305313 EMBL· GenBank· DDBJ | AGS55987.1 EMBL· GenBank· DDBJ | mRNA | ||
AL928843 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL929208 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |