E9PTA2 · TRPM2_RAT
- ProteinTransient receptor potential cation channel subfamily M member 2
- GeneTrpm2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1507 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Nonselective, voltage-independent cation channel that mediates Na+ and Ca2+ influx, leading to increased cytoplasmic Ca2+ levels (PubMed:11804595, PubMed:16260005, PubMed:16601673, PubMed:16651700, PubMed:19454650).
Functions as a ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca2+ binding to trigger channel opening. Extracellular calcium passes through the channel and increases channel activity (By similarity).
Also contributes to Ca2+ release from intracellular stores in response to ADP-ribose (PubMed:19454650).
Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (Probable). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (PubMed:25562606).
Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673).
Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:16260005, PubMed:16601673, PubMed:25562606).
The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (By similarity).
Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (PubMed:16601673).
Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (By similarity).
Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its function in increasing cytoplasmic Ca2+ and Zn2+ levels (By similarity).
Confers susceptibility to cell death following oxidative stress (PubMed:11804595, PubMed:16651700, PubMed:19454650, PubMed:25562606).
Functions as a ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca2+ binding to trigger channel opening. Extracellular calcium passes through the channel and increases channel activity (By similarity).
Also contributes to Ca2+ release from intracellular stores in response to ADP-ribose (PubMed:19454650).
Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (Probable). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (PubMed:25562606).
Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673).
Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:16260005, PubMed:16601673, PubMed:25562606).
The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (By similarity).
Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (PubMed:16601673).
Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (By similarity).
Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its function in increasing cytoplasmic Ca2+ and Zn2+ levels (By similarity).
Confers susceptibility to cell death following oxidative stress (PubMed:11804595, PubMed:16651700, PubMed:19454650, PubMed:25562606).
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransient receptor potential cation channel subfamily M member 2
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionE9PTA2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Detected at the cell membrane and in intracellular vesicles in cortical neurons. Detected on neuronal cell bodies and neurites (PubMed:16651700).
Detected on the cell membrane in polymorphonuclear neutrophils. Detected on cytoplasmic vesicles and lysosomes in immature bone marrow dendritic cells (By similarity).
Detected on the cell membrane in polymorphonuclear neutrophils. Detected on cytoplasmic vesicles and lysosomes in immature bone marrow dendritic cells (By similarity).
Features
Showing features for topological domain, intramembrane, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-751 | Cytoplasmic | ||||
Sequence: MEPLDQRRTDSDQEEGFGVQSRRATDLGMVPNLRRSNSSLCKSRRLLCSFSSEKQENLSSWIPENIKKKECVYFVESSKLSDAGKVVCECGYTHEQHIEVAIKPHTFQGKEWDPKKHVHEMPTDAFGDIVFTGLSQKVGKYVRLSQDTSSIVIYQLMTQHWGLDVPSLLISVTGGAKNFNMKLRLKSIFRRGLVKVAQTTGAWIITGGSHTGVMKQVGEAVRDFSLSSSCKEGDVITIGIATWGTIHNREALIHPMGGFPAEYMLDEEGQGNLTCLDSNHSHFILVDDGTHGQYGVEIPLRTKLEKFISEQTKERGGVAIKIPIVCVVLEGGPGTLHTIYNAITNGTPCVIVEGSGRVADVIAQVAALPVSEITISLIQQKLSVFFQEMFETFTENQIVEWTKKIQDIVRRRQLLTVFREGKDGQQDVDVAILQALLKASRSQDHFGHENWDHQLKLAVAWNRVDIARSEIFTDEWQWKPSDLHPMMTAALISNKPEFVRLFLENGVRLKEFVTWDTLLCLYENLEPSCLFHSKLQKVLAEEHERLAYASETPRLQMHHVAQVLRELLGDSTQLLYPRPRYTDRPRLSLPMPHIKLNVQGVSLRSLYKRSTGHVTFTIDPVRDLLIWAIIQNHRELAGIIWAQSQDCTAAALACSKILKELSKEEEDTDSSEEMLALADEFEHRAIGVFTECYRKDEERAQKLLVRVSEAWGKTTCLQLALEAKDMKFVSHGGIQAFLTKVWWGQLCVDNG | ||||||
Intramembrane | 752-768 | |||||
Sequence: LWRIILCMLAFPLLFTG | ||||||
Topological domain | 769-793 | Cytoplasmic | ||||
Sequence: FISFREKRLQALCRLARVRAFFNAP | ||||||
Transmembrane | 794-814 | Helical | ||||
Sequence: VVIFYLNILSYFAFLCLFAYV | ||||||
Topological domain | 815-825 | Extracellular | ||||
Sequence: LMVDFQPSPSW | ||||||
Transmembrane | 826-846 | Helical | ||||
Sequence: CEYLIYLWLFSLVCEETRQLF | ||||||
Topological domain | 847-865 | Cytoplasmic | ||||
Sequence: YDPDGCGLMKMASLYFSDF | ||||||
Transmembrane | 866-886 | Helical | ||||
Sequence: WNKLDVGAILLFIAGLTCRLI | ||||||
Topological domain | 887-894 | Extracellular | ||||
Sequence: PATLYPGR | ||||||
Transmembrane | 895-915 | Helical | ||||
Sequence: IILSLDFIMFCLRLMHIFTIS | ||||||
Topological domain | 916-927 | Cytoplasmic | ||||
Sequence: KTLGPKIIIVKR | ||||||
Transmembrane | 928-948 | Helical | ||||
Sequence: MMKDVFFFLFLLAVWVVSFGV | ||||||
Topological domain | 949-968 | Extracellular | ||||
Sequence: AKQAILIHNESRVDWIFRGV | ||||||
Intramembrane | 969-983 | Pore-forming | ||||
Sequence: IYHSYLTIFGQIPTY | ||||||
Topological domain | 984-1020 | Extracellular | ||||
Sequence: IDGVNFSMDQCSPNGTDPYKPKCPESDWTGQAPAFPE | ||||||
Transmembrane | 1021-1042 | Helical | ||||
Sequence: WLTVTLLCLYLLFANILLLNLL | ||||||
Topological domain | 1043-1077 | Cytoplasmic | ||||
Sequence: IAMFNYTFQEVQEHTDQIWKFQRHDLIEEYHGRPP | ||||||
Intramembrane | 1078-1096 | |||||
Sequence: APPPLILLSHLQLLIKRIV | ||||||
Topological domain | 1097-1507 | Cytoplasmic | ||||
Sequence: LKIPAKRHKQLKNKLEKNEEAALLSWELYLKENYLQNQQYQHKQRPEQKIQDISEKVDTMVDLLDMDRVKRSGSTEQRLASLEEQVTQMGRSLHWIVTTLKDSGFGSGAGALTLAQRAFDEPDAELSIRKKGEEGGDGYHVSARHLLYPDARIMRFPVPNEKVPWEAEFLIYDPPFYTAEKKDATLTDPVGDTAEPLSKINYNVVDGLMDRCSFHGTYVVQYGFPLNPMGRTGLRGRGSLSWFGPNHTLQPVVTRWKRNQGGGICRKSVRKMLEVLVVKLPQSEHWALPGGSREPGKMLPRKLKQVLQQEYWVTFETLLRQGTEVYKGYVDDPRNTDNAWIETVAVSIHFQDQNDVELKRLEENLQTHDPKESARGLEMSTEWQVVDRRIPLYVNHKKILQKVASLFGAHF |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000438192 | 1-1507 | Transient receptor potential cation channel subfamily M member 2 | |||
Sequence: MEPLDQRRTDSDQEEGFGVQSRRATDLGMVPNLRRSNSSLCKSRRLLCSFSSEKQENLSSWIPENIKKKECVYFVESSKLSDAGKVVCECGYTHEQHIEVAIKPHTFQGKEWDPKKHVHEMPTDAFGDIVFTGLSQKVGKYVRLSQDTSSIVIYQLMTQHWGLDVPSLLISVTGGAKNFNMKLRLKSIFRRGLVKVAQTTGAWIITGGSHTGVMKQVGEAVRDFSLSSSCKEGDVITIGIATWGTIHNREALIHPMGGFPAEYMLDEEGQGNLTCLDSNHSHFILVDDGTHGQYGVEIPLRTKLEKFISEQTKERGGVAIKIPIVCVVLEGGPGTLHTIYNAITNGTPCVIVEGSGRVADVIAQVAALPVSEITISLIQQKLSVFFQEMFETFTENQIVEWTKKIQDIVRRRQLLTVFREGKDGQQDVDVAILQALLKASRSQDHFGHENWDHQLKLAVAWNRVDIARSEIFTDEWQWKPSDLHPMMTAALISNKPEFVRLFLENGVRLKEFVTWDTLLCLYENLEPSCLFHSKLQKVLAEEHERLAYASETPRLQMHHVAQVLRELLGDSTQLLYPRPRYTDRPRLSLPMPHIKLNVQGVSLRSLYKRSTGHVTFTIDPVRDLLIWAIIQNHRELAGIIWAQSQDCTAAALACSKILKELSKEEEDTDSSEEMLALADEFEHRAIGVFTECYRKDEERAQKLLVRVSEAWGKTTCLQLALEAKDMKFVSHGGIQAFLTKVWWGQLCVDNGLWRIILCMLAFPLLFTGFISFREKRLQALCRLARVRAFFNAPVVIFYLNILSYFAFLCLFAYVLMVDFQPSPSWCEYLIYLWLFSLVCEETRQLFYDPDGCGLMKMASLYFSDFWNKLDVGAILLFIAGLTCRLIPATLYPGRIILSLDFIMFCLRLMHIFTISKTLGPKIIIVKRMMKDVFFFLFLLAVWVVSFGVAKQAILIHNESRVDWIFRGVIYHSYLTIFGQIPTYIDGVNFSMDQCSPNGTDPYKPKCPESDWTGQAPAFPEWLTVTLLCLYLLFANILLLNLLIAMFNYTFQEVQEHTDQIWKFQRHDLIEEYHGRPPAPPPLILLSHLQLLIKRIVLKIPAKRHKQLKNKLEKNEEAALLSWELYLKENYLQNQQYQHKQRPEQKIQDISEKVDTMVDLLDMDRVKRSGSTEQRLASLEEQVTQMGRSLHWIVTTLKDSGFGSGAGALTLAQRAFDEPDAELSIRKKGEEGGDGYHVSARHLLYPDARIMRFPVPNEKVPWEAEFLIYDPPFYTAEKKDATLTDPVGDTAEPLSKINYNVVDGLMDRCSFHGTYVVQYGFPLNPMGRTGLRGRGSLSWFGPNHTLQPVVTRWKRNQGGGICRKSVRKMLEVLVVKLPQSEHWALPGGSREPGKMLPRKLKQVLQQEYWVTFETLLRQGTEVYKGYVDDPRNTDNAWIETVAVSIHFQDQNDVELKRLEENLQTHDPKESARGLEMSTEWQVVDRRIPLYVNHKKILQKVASLFGAHF | ||||||
Disulfide bond | 994↔1006 | |||||
Sequence: CSPNGTDPYKPKC |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Basic and acidic residues | ||||
Sequence: MEPLDQRRTDSDQEEGFGV | ||||||
Region | 1-24 | Disordered | ||||
Sequence: MEPLDQRRTDSDQEEGFGVQSRRA | ||||||
Domain | 1351-1502 | Nudix hydrolase | ||||
Sequence: RWKRNQGGGICRKSVRKMLEVLVVKLPQSEHWALPGGSREPGKMLPRKLKQVLQQEYWVTFETLLRQGTEVYKGYVDDPRNTDNAWIETVAVSIHFQDQNDVELKRLEENLQTHDPKESARGLEMSTEWQVVDRRIPLYVNHKKILQKVASL | ||||||
Motif | 1387-1408 | Nudix box | ||||
Sequence: GSREPGKMLPRKLKQVLQQEYW |
Domain
The cytosolic nudix box binds ADP-ribose and is required for channel activation by ADP-ribose.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,507
- Mass (Da)172,259
- Last updated2015-07-22 v3
- Checksum3E54E154A0166F99
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2UH90 | A0A8L2UH90_RAT | Trpm2 | 1508 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Basic and acidic residues | ||||
Sequence: MEPLDQRRTDSDQEEGFGV | ||||||
Sequence conflict | 783 | in Ref. 2; AAW65801 and 1; BAE72117 | ||||
Sequence: L → P | ||||||
Sequence conflict | 1210 | in Ref. 2; AAW65801 | ||||
Sequence: L → LA | ||||||
Sequence conflict | 1374 | in Ref. 2; AAW65801 and 1; BAE72117 | ||||
Sequence: V → M |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB193179 EMBL· GenBank· DDBJ | BAE72117.1 EMBL· GenBank· DDBJ | mRNA | ||
AY749166 EMBL· GenBank· DDBJ | AAW65801.1 EMBL· GenBank· DDBJ | mRNA | ||
AABR07044580 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AABR07044581 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AABR07072820 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC109383 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |