The following text describes a protein:
Function:
Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels. Functions as a ligand-gated ion channel, gated by intracellular adenosine diphosphate ribose (ADP-ribose), Ca(2+), warm temperature, and oxidative stress. The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (By similarity). Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening. Extracellular Ca(2+) passes through the channel and increases channel activity (By similarity). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose. Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels. Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (By similarity). 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 Ca(2+) levels. 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 Ca(2+) levels. 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 Ca(2+) and Zn(2+) levels (By similarity). Confers susceptibility to cell death following oxidative stress.
Subcellular Localization:
Cell membrane; Multi-pass membrane protein. Perikaryon. Cell projection. Cytoplasmic vesicle. Lysosome. Note=Detected at the cell membrane and in intracellular vesicles in cortical neurons. Detected on neuronal cell bodies and neurites (By similarity). Detected on the cell membrane in polymorphonuclear neutrophils. Detected on cytoplasmic vesicles and lysosomes in immature bone marrow dendritic cells.
Domain:
Contains two binding sites for ADP-ribose, one in the N-terminal part of the channel and the other in the C-terminal nudix hydrolase domain. Both sites seem to have a role in channel opening, but the interaction of ADP-ribose with the N-terminal site is absolutely required for channel activation.
Sequence:
MESLDRRRTGSEQEEGFGVQSRRATDLGMVPNLRRSNSSLCKSRRFLCSFSSEKQENLSSWIPENIKKKECVYFVESSKLSDAGKVVCACGYTHEQHLEVAIKPHTFQGKEWDPKKHVQEMPTDAFGDIVFTDLSQKVGKYVRVSQDTPSSVIYQLMTQHWGLDVPNLLISVTGGAKNFNMKLRLKSIFRRGLVKVAQTTGAWIITGGSHTGVMKQVGEAVRDFSLSSSCKEGEVITIGVATWGTIHNREGLIHPMGGFPAEYMLDEEGQGNLTCLDSNHSHFILVDDGTHGQYGVEIPLRTKLEKFISEQTKERGGVAIKIPIVCVVLEGGPGTLHTIYNAINNGTPCVIVEGSGRVADVIAQVATLPVSEITISLIQQKLSIFFQEMFETFTENQIVEWTKKIQDIVRRRQLLTIFREGKDGQQDVDVAILQALLKASRSQDHFGHENWDHQLKLAVAWNRVDIARSEIFTDEWQWKPADLHPMMTAALISNKPEFVRLFLENGVRLKEFVTWDTLLCLYENLEPSCLFHSKLQKVLAEEQRLAYASATPRLHMHHVAQVLRELLGDSTQLLYPRPRYTDRPRLSMTVPHIKLNVQGVSLRSLYKRSTGHVTFTIDPVRDLLIWAVIQNHRELAGIIWAQSQDCTAAALACSKILKELSKEEEDTDSSEEMLALADEFEHRAIGVFTECYRKDEERAQKLLVRVSEAWGKTTCLQLALEAKDMKFVSHGGIQAFLTKVWWGQLCVDNGLWRIILCMLAFPLLFTGFISFREKRLQALCRPARVRAFFNAPVVIFHMNILSYFAFLCLFAYVLMVDFQPSPSWCEYLIYLWLFSLVCEETRQLFYDPDGCGLMKMASLYFSDFWNKLDVGAILLFIVGLTCRLIPATLYPGRIILSLDFIMFCLRLMHIFTISKTLGPKIIIVKRMMKDVFFFLFLLAVWVVSFGVAKQAILIHNESRVDWIFRGVVYHSYLTIFGQIPTYIDGVNFSMDQCSPNGTDPYKPKCPESDWTGQAPAFPEWLTVTLLCLYLLFANILLLNLLIAMFNYTFQEVQEHTDQIWKFQRHDLIEEYHGRPPAPPPLILLSHLQLLIKRIVLKIPAKRHKQLKNKLEKNEETALLSWELYLKENYLQNQQYQQKQRPEQKIQDISEKVDTMVDLLDMDQVKRSGSTEQRLASLEEQVTQVTRALHWIVTTLKDSGFGSGAGALTLAPQRAFDEPDAELSIRRKVEEPGDGYHVSARHLLYPNARIMRFPVPNEKVPWAAEFLIYDPPFYTAEKDVALTDPVGDTAEPLSKISYNVVDGPTDRRSFHGVYVVEYGFPLNPMGRTGLRGRGSLSWFGPNHTLQPVVTRWKRNQGGAICRKSVRKMLEVLVMKLPRSEHWALPGGSREPGEMLPRKLKRVLRQEFWVAFETLLMQGTEVYKGYVDDPRNTDNAWIETVAVSIHFQDQNDMELKRLEENLHTHDPKELTRDLKLSTEWQVVDRRIPLYANHKTILQKVASLFGAHF