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transient receptor potential cation channel subfamily M member 2 (TrpM2, long transient receptor potential channel 2, LTrpC2, LTrpC-2, transient receptor potential channel 7, TrpC7, estrogen-responsive element-associated gene 1 protein, EREG1, KNP3)
Function:
1) nonselective, voltage-independent cation channel
2) mediates Na+ & Ca+2 influx in response to oxidative stress
3) intracellular Ca+2 activates channel
4) activated by ADP-ribose, NAD+, reactive nitrogen species & arachidonic acid
5) ADP-ribose pyrophosphatase activity
6) inactivated by intracellular ATP
7) confers susceptibility to cell death following oxidative stress
ADP-ribose + H2O AMP + D-ribose-5-phosphate
Cofactor NAD+
Kinetic parameters:
- KM=100 uM for ADP-ribose
- Vmax=0.1 umol/min/mg enzyme;
Alternative splicing: named isoforms=3
1) isoform 2 not regulated by ADP-ribose .
2) isoform 1 can interact with isoform 3
- interaction decreases Ca+2 influx through isoform 1 & suppresses susceptibility to oxidative stress-induced cell death
Compartment: membrane
Expression:
- expressed in brain, neutrophils > bone marrow, spleen, heart, liver, lung
- isoform 2 is found in neutrophils
General
Ca+2 channel
Na+ channel
transient receptor potential cation channel subfamily M (TRPM)
transmembrane 6 protein
Properties
SIZE: MW = 171 kD
entity length = 1503 aa
COMPARTMENT: plasma membrane
MOTIF: cytoplasmic domain {1-752}
transmembrane domain {753-773}
exoplasmic loop {774-795}
transmembrane domain {796-816}
cytoplasmic loop {817-872}
transmembrane domain {873-893}
exoplasmic loop {894-896}
transmembrane domain {897-917}
cytoplasmic loop {918-936}
transmembrane domain {937-957}
exoplasmic loop {958-1025}
transmembrane domain {1026-1046}
cytoplasmic domain {1047-1503}
MOTIF: NUDIX HYDROLASE {1197-1503}
cofactor-binding site [1390-1412]
COFACTOR-BOUND: NAD
ION-PERMEABILITY: Ca+2
Database Correlations
OMIM 603749
UniProt O94759
Pfam PF00520
ENZYME 3.6.1.13
References
UniProt :accession O94759