A7T1N0 · TMP2L_NEMVE
- ProteinTransient receptor potential cation channel subfamily M member-like 2
- GeneTRPM2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1551 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Nonselective, voltage-independent cation channel that mediates Ca2+ and to a lesser extent Na+ influx, leading to increased cytoplasmic Ca2+ levels (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897).
Functions as a ligand-gated ion channel (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897).
Binding of ADP-ribose causes a conformation change; the channel is primed but still requires Ca2+ binding to trigger channel opening (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897).
May have ADP-ribose pyrophosphatase activity which reduces ADP-ribose levels induced by oxidative stress, thus preventing the channel activation by reactive oxygen species (PubMed:25620041, PubMed:27333281).
Functions as a ligand-gated ion channel (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897).
Binding of ADP-ribose causes a conformation change; the channel is primed but still requires Ca2+ binding to trigger channel opening (PubMed:25620041, PubMed:27333281, PubMed:28775320, PubMed:29745897).
May have ADP-ribose pyrophosphatase activity which reduces ADP-ribose levels induced by oxidative stress, thus preventing the channel activation by reactive oxygen species (PubMed:25620041, PubMed:27333281).
Activity regulation
Activated by phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:29745897).
Although PIP2 is essential for the channel activation, its contribution to the level of channel activity is minimal (PubMed:29745897).
Also activated by diphosphate ribose-2'-phosphate (PubMed:27333281).
Upon binding to ADPR, channel activation requires only a short initial cytosolic Ca2+ increase, then the activation is sustained by the uptake of extracellular Ca2+ (PubMed:25620041, PubMed:29745897).
Activated by 2-aminoethyl diphenylborinate (2-APB) in a Ca2+-dependent manner (PubMed:28775320).
2-APB prevents the inactivation of the channel (PubMed:28775320).
Although PIP2 is essential for the channel activation, its contribution to the level of channel activity is minimal (PubMed:29745897).
Also activated by diphosphate ribose-2'-phosphate (PubMed:27333281).
Upon binding to ADPR, channel activation requires only a short initial cytosolic Ca2+ increase, then the activation is sustained by the uptake of extracellular Ca2+ (PubMed:25620041, PubMed:29745897).
Activated by 2-aminoethyl diphenylborinate (2-APB) in a Ca2+-dependent manner (PubMed:28775320).
2-APB prevents the inactivation of the channel (PubMed:28775320).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | plasma membrane | |
Molecular Function | ADP-ribose diphosphatase activity | |
Molecular Function | ligand-gated calcium channel activity | |
Molecular Function | ligand-gated sodium channel activity | |
Molecular Function | metal ion binding | |
Biological Process | calcium ion transmembrane transport | |
Biological Process | sodium ion transmembrane transport |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameTransient receptor potential cation channel subfamily M member-like 2
- Short namesnvTRPM2
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Cnidaria > Anthozoa > Hexacorallia > Actiniaria > Edwardsiidae > Nematostella
Accessions
- Primary accessionA7T1N0
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, intramembrane, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-714 | Cytoplasmic | ||||
Sequence: MGKDSFTPLYDGGDSSHVHLNKFGSNQLSQSKKSWIARNFSRRECIRFVPKSHDVSRCKCGRPRERHSQQALESGQGSEEWNVASCTTKHPTNAYGEIDFEGYGGQKRAPYLRMSHDTDANLVITLMLKRWNLEIPNLVISVTGGAKSFVLKPRLREMFRRGLIKAAKTTGAWIITGGTNTGVMKHVGEAVKEQQLMFGSDTQVNVIGIATWGIVDKQSDLISEKNGKYPALYSMEPTPGHQGAMLDPNHSHFFLVDDGTEGKYGVEIGMRSRIEEAIMKVKTDSRSEAGSIGVPVVLLVLEGGPNTVATMYELIKKKVPAVVIDGSGRAASVVGFAYNHTIKRNVDGQTINVIDPQYEDEVRAKVVEVFGAKGADKTYSMIKDVLEDEKMISVYSLDGEISQDIDLAILKALLKANRSSPVAQLNLALAWNRIDLAKSDIFTEEQQWTTETLSAAMLTALLDDKAEFAELFLQNGLSMREFLSLDILCKLYAEVPGNTTIKPLLQKEMGKRQVKTIDMDVVGEVIEELMGDMFESYYRKDGHYFGELASYAEGLVLKNRKSSKDLLANINRIDPLPTPYLDVFLWAVLCNRRELARVLWEAGREPMAAALMASRLLKRMASRAQEDNTITDISSDLYDHARLFEERAVGVLDECFNENETLSQTLLVRELDHYSRMTALELAVSAESQDFIAHTSCQVLLTRLWMGTMAMNTR | ||||||
Intramembrane | 715-730 | |||||
Sequence: WWKVLVCLYLPVLIFP | ||||||
Topological domain | 731-837 | Cytoplasmic | ||||
Sequence: IIYFVPDEQHERQAAEREHQKSLNQKSSKVKSHKEKNDAPVVPVYRSKEEKAVSNDEEARVGTENEEEDFQLEDYIPEIREDDSMEVIMRNKKLGFCDRIMHFYSAP | ||||||
Transmembrane | 838-858 | Helical | ||||
Sequence: FSKFVGNVVGYLAFIFLYAYV | ||||||
Topological domain | 859-877 | Extracellular | ||||
Sequence: VLFNFPRFDPAKTLGGIHP | ||||||
Transmembrane | 878-898 | Helical | ||||
Sequence: TEIVLYFWVFTILIEEIRQLA | ||||||
Topological domain | 899-916 | Cytoplasmic | ||||
Sequence: AKPPKYIKDKVSVYFSDT | ||||||
Transmembrane | 917-937 | Helical | ||||
Sequence: WNFVDIFSLTVFIIAIILRFF | ||||||
Topological domain | 938-947 | Extracellular | ||||
Sequence: TNSRIFTASR | ||||||
Transmembrane | 948-968 | Helical | ||||
Sequence: IILSLDIIFFIVRSLQIFSVN | ||||||
Topological domain | 969-980 | Cytoplasmic | ||||
Sequence: RLLGPKLVMIQK | ||||||
Transmembrane | 981-1001 | Helical | ||||
Sequence: MMQDLAQFIIILAVFTIAYGI | ||||||
Topological domain | 1002-1018 | Extracellular | ||||
Sequence: ALHAVMFPSPGIYARNN | ||||||
Intramembrane | 1019-1034 | Pore-forming | ||||
Sequence: TWVTITSVVQYPYWQM | ||||||
Topological domain | 1035-1059 | Extracellular | ||||
Sequence: YGELFLDEIQGEKPKEFGEVDPDGR | ||||||
Transmembrane | 1060-1080 | Helical | ||||
Sequence: WLSPLLLAIYMVFTNILLLNL | ||||||
Topological domain | 1081-1116 | Cytoplasmic | ||||
Sequence: LIAIFNYTFERVQEDSDKVWKFQRYDLVQEYHSRPV | ||||||
Intramembrane | 1117-1135 | |||||
Sequence: FAPPLVLLGHILIFIRWVW | ||||||
Topological domain | 1136-1551 | Cytoplasmic | ||||
Sequence: RMCRCGHPPRGSTMKIGLSPAEMEQMDNWEFQAAEMYIHQQQQKNSGTLEERVRALGDRVDCINSQLNRVLDSMSGTRAHALTDGNGLEGGHDSEGRLARMEVELSSNSESLQKILALLQQQPPVKGQAAVPIQLTLLHYKARSSPYPGSTAKRFAVQDNMVDWQVPFPDYKPVNYTAPVVLANPVWADKDLMAMSPRPELPYNQMDHTCNVNRVSYNGTYVVKDGLPLNPMGRTGMQGRGLLGRFGPNHAADPVVTRWKRTSAGVMLQGGKKVLEFVAIQRKDNNQWAIPGGMVEPGQLVTQALKAEFGEEAMAKLNVSQEEKERIAKQIERLFQQGQEIYKGYVDDPRNTDNAWMETVAVNFHDDKGDLFGDITLQAGDDAAAVRWQRVSGNIPLYASHVSILEKVAKMRDAAF |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 896 | Severe loss of Ca2+ sensitivity and increased sensitivity to phosphatidylinositol 4,5-bisphosphate-mediated activation. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 908 | Severe reduction in ADP-ribose-mediated channel activation. | ||||
Sequence: K → N | ||||||
Mutagenesis | 918 | Severe loss of Ca2+ sensitivity and increased sensitivity to phosphatidylinositol 4,5-bisphosphate-mediated activation. | ||||
Sequence: N → A | ||||||
Mutagenesis | 921 | Severe loss of Ca2+ sensitivity and increased sensitivity to phosphatidylinositol 4,5-bisphosphate-mediated activation. | ||||
Sequence: D → A | ||||||
Mutagenesis | 1037-1039 | Mild decrease in channel activation. | ||||
Sequence: ELF → QLP | ||||||
Mutagenesis | 1040-1042 | Induces fast inactivation of the channel. | ||||
Sequence: LDE → GY | ||||||
Mutagenesis | 1047 | Does not affect channel activity. | ||||
Sequence: K → A or E | ||||||
Mutagenesis | 1110 | Mild loss of Ca2+ sensitivity and increased sensitivity to phosphatidylinositol 4,5-bisphosphate-mediated activation. | ||||
Sequence: E → A | ||||||
Mutagenesis | 1149-1463 | Induces transient spontaneous channel activity. Does not affect channel activity by ADP-ribose. Acquires sensitivity to oxidative stress. In response to oxidative stress, induces intracellular Ca2+ oscillations instead of a sustained Ca2+ increase. | ||||
Sequence: Missing | ||||||
Mutagenesis | 1365 | Does not affect channel activity. Acquires sensitivity to oxidative stress. | ||||
Sequence: N → D | ||||||
Mutagenesis | 1438 | Does not affect channel activity by ADP-ribose. Acquires sensitivity to oxidative stress. | ||||
Sequence: Q → R | ||||||
Mutagenesis | 1442-1446 | Does not affect channel activity by ADP-ribose. Acquires sensitivity to oxidative stress. | ||||
Sequence: AEFGE → RILRQ |
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000446910 | 1-1551 | Transient receptor potential cation channel subfamily M member-like 2 | |||
Sequence: MGKDSFTPLYDGGDSSHVHLNKFGSNQLSQSKKSWIARNFSRRECIRFVPKSHDVSRCKCGRPRERHSQQALESGQGSEEWNVASCTTKHPTNAYGEIDFEGYGGQKRAPYLRMSHDTDANLVITLMLKRWNLEIPNLVISVTGGAKSFVLKPRLREMFRRGLIKAAKTTGAWIITGGTNTGVMKHVGEAVKEQQLMFGSDTQVNVIGIATWGIVDKQSDLISEKNGKYPALYSMEPTPGHQGAMLDPNHSHFFLVDDGTEGKYGVEIGMRSRIEEAIMKVKTDSRSEAGSIGVPVVLLVLEGGPNTVATMYELIKKKVPAVVIDGSGRAASVVGFAYNHTIKRNVDGQTINVIDPQYEDEVRAKVVEVFGAKGADKTYSMIKDVLEDEKMISVYSLDGEISQDIDLAILKALLKANRSSPVAQLNLALAWNRIDLAKSDIFTEEQQWTTETLSAAMLTALLDDKAEFAELFLQNGLSMREFLSLDILCKLYAEVPGNTTIKPLLQKEMGKRQVKTIDMDVVGEVIEELMGDMFESYYRKDGHYFGELASYAEGLVLKNRKSSKDLLANINRIDPLPTPYLDVFLWAVLCNRRELARVLWEAGREPMAAALMASRLLKRMASRAQEDNTITDISSDLYDHARLFEERAVGVLDECFNENETLSQTLLVRELDHYSRMTALELAVSAESQDFIAHTSCQVLLTRLWMGTMAMNTRWWKVLVCLYLPVLIFPIIYFVPDEQHERQAAEREHQKSLNQKSSKVKSHKEKNDAPVVPVYRSKEEKAVSNDEEARVGTENEEEDFQLEDYIPEIREDDSMEVIMRNKKLGFCDRIMHFYSAPFSKFVGNVVGYLAFIFLYAYVVLFNFPRFDPAKTLGGIHPTEIVLYFWVFTILIEEIRQLAAKPPKYIKDKVSVYFSDTWNFVDIFSLTVFIIAIILRFFTNSRIFTASRIILSLDIIFFIVRSLQIFSVNRLLGPKLVMIQKMMQDLAQFIIILAVFTIAYGIALHAVMFPSPGIYARNNTWVTITSVVQYPYWQMYGELFLDEIQGEKPKEFGEVDPDGRWLSPLLLAIYMVFTNILLLNLLIAIFNYTFERVQEDSDKVWKFQRYDLVQEYHSRPVFAPPLVLLGHILIFIRWVWRMCRCGHPPRGSTMKIGLSPAEMEQMDNWEFQAAEMYIHQQQQKNSGTLEERVRALGDRVDCINSQLNRVLDSMSGTRAHALTDGNGLEGGHDSEGRLARMEVELSSNSESLQKILALLQQQPPVKGQAAVPIQLTLLHYKARSSPYPGSTAKRFAVQDNMVDWQVPFPDYKPVNYTAPVVLANPVWADKDLMAMSPRPELPYNQMDHTCNVNRVSYNGTYVVKDGLPLNPMGRTGMQGRGLLGRFGPNHAADPVVTRWKRTSAGVMLQGGKKVLEFVAIQRKDNNQWAIPGGMVEPGQLVTQALKAEFGEEAMAKLNVSQEEKERIAKQIERLFQQGQEIYKGYVDDPRNTDNAWMETVAVNFHDDKGDLFGDITLQAGDDAAAVRWQRVSGNIPLYASHVSILEKVAKMRDAAF | ||||||
Glycosylation | 1017 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
PTM databases
Interaction
Structure
Family & Domains
Features
Showing features for region, motif, coiled coil, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 744-767 | Disordered | ||||
Sequence: AAEREHQKSLNQKSSKVKSHKEKN | ||||||
Motif | 1035-1037 | Selectivity filter | ||||
Sequence: YGE | ||||||
Motif | 1040-1042 | Prevents fast channel inactivation | ||||
Sequence: LDE | ||||||
Coiled coil | 1184-1209 | |||||
Sequence: LEERVRALGDRVDCINSQLNRVLDSM | ||||||
Domain | 1394-1546 | Nudix hydrolase | ||||
Sequence: WKRTSAGVMLQGGKKVLEFVAIQRKDNNQWAIPGGMVEPGQLVTQALKAEFGEEAMAKLNVSQEEKERIAKQIERLFQQGQEIYKGYVDDPRNTDNAWMETVAVNFHDDKGDLFGDITLQAGDDAAAVRWQRVSGNIPLYASHVSILEKVAKM | ||||||
Motif | 1428-1449 | Nudix box | ||||
Sequence: GMVEPGQLVTQALKAEFGEEAM |
Domain
The Nudix hydrolase domain is dispensable for ADP-ribose-dependent channel activation. May be involved in the regulation of ADP-ribose intracellular levels. Essential to prevent response to oxidative stress.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,551
- Mass (Da)175,439
- Last updated2007-10-02 v1
- Checksum31E4B2755128372C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DS470128 EMBL· GenBank· DDBJ | EDO30135.1 EMBL· GenBank· DDBJ | Genomic DNA |