NUDT9 antibody - N-terminal region (ARP35539_P050)
- Known as:
- NUDT9 (anti-) - N-terminal region (ARP35539_P050)
- Catalog number:
- arp35539_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- NUDT9 antibody - N-terminal region (ARP35539_P050)
Related genes to: NUDT9 antibody - N-terminal region (ARP35539_P050)
- Gene:
- NUDT9 NIH gene
- Name:
- nudix hydrolase 9
- Previous symbol:
- -
- Synonyms:
- MGC3037
- Chromosome:
- 4q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-02
- Date modifiied:
- 2015-11-13
- Gene:
- TRPM2 NIH gene
- Name:
- transient receptor potential cation channel subfamily M member 2
- Previous symbol:
- TRPC7
- Synonyms:
- KNP3, LTRPC2, NUDT9L1, NUDT9H, EREG1
- Chromosome:
- 21q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-23
- Date modifiied:
- 2016-01-28
Related products to: NUDT9 antibody - N-terminal region (ARP35539_P050)
Related articles to: NUDT9 antibody - N-terminal region (ARP35539_P050)
- Transient receptor potential (TRP) ion channels of the melastatin family (TRPM) have eight members in mammals with a broad spectrum of functions. We investigated the evolution of this complex gene family across metazoans. The characteristic aminoterminal melastatin domain and the carboxyterminal NUDT9 homology domain with similarity to ADP-ribose pyrophosphatase were added to the common ancestor of TRPM and its sister channel TRPS. Gene duplications before the origin of bilaterians resulted in four TRPM genes: α, β, βlike, and γ. The two latter were discovered in this study. All four and TRPS are present in extant mollusks, while differential losses occurred in the other animal lineages. TRPS, TRPMβlike, and TRPMγ were lost in early chordates, meaning that the vertebrate ancestor started with TRPMα and β, both of which were duplicated before the first vertebrate tetraploidization 1R. The ancestor of the micro-RNA genes mir-211 and mir-204 was inserted in an intron of the ancestor of TRPM1/TRPM3. The TRPM6/TRPM7 ancestor acquired a kinase domain, probably a copy of the syntenic alpha protein kinase ALPK2/3 ancestor gene. Vertebrate 1R and gnathostome 2R together with local gene duplication and losses resulted in eight TRPM (TRPM1 to 8) in the gnathostome ancestor. In cyclostomes, extensive gene losses after the hexaploidization led to four TRPM. The teleost-specific tetraploidization 3R generated further TRPM ohnologs. The NUDT9 homology domain is retained in TRPM2 and TRPS but was lost repeatedly during TRPM evolution. Thus, the TRPM family displays considerable evolutionary variation with regard to gene and domain gains and losses. - Source: PubMed
Morini MarinaBergqvist ChristinaAsturiano Juan FDufour SylvieLarhammar Dan - Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP-ribose with high open probability and an enzyme module (NUDT9-H domain) consuming ADP-ribose at a remarkably slow rate. Using time-resolved cryogenic-electron microscopy, we captured a complete series of structural snapshots of gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. The slow kinetics of the NUDT9-H enzyme module confers a self-regulatory mechanism: ADPR binding triggers NUDT9-H tetramerization, promoting channel opening, while subsequent hydrolysis reduces local ADPR, inducing channel closure. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADP-ribose hydrolase module in early species to a fully integrated component of a gating ring essential for channel activation in advanced species. - Source: PubMed
Publication date: 2024/05/21
Huang YiheKumar SushantLee JunukLü WeiDu Juan - Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins. - Source: PubMed
Publication date: 2024/04/26
Ma ChengLuo YanpingZhang CongyiCheng ChengHua NingLiu XiaocaoWu JiananQin LuyingYu PeilinLuo JianhongYang FanJiang Lin-HuaZhang GuojieYang Wei - Different cell channels and transporters tightly regulate cytoplasmic levels and the intraorganelle distribution of cations. Perturbations in these processes lead to human diseases that are frequently associated with kidney impairment. The family of melastatin-related transient receptor potential (TRPM) channels, which has eight members in mammals (TRPM1-TRPM8), includes ion channels that are highly permeable to divalent cations, such as Ca, Mg and Zn (TRPM1, TRPM3, TRPM6 and TRPM7), non-selective cation channels (TRPM2 and TRPM8) and monovalent cation-selective channels (TRPM4 and TRPM5). Three family members contain an enzymatic protein moiety: TRPM6 and TRPM7 are fused to α-kinase domains, whereas TRPM2 is linked to an ADP-ribose-binding NUDT9 homology domain. TRPM channels also function as crucial cellular sensors involved in many physiological processes, including mineral homeostasis, blood pressure, cardiac rhythm and immunity, as well as photoreception, taste reception and thermoreception. TRPM channels are abundantly expressed in the kidney. Mutations in TRPM genes cause several inherited human diseases, and preclinical studies in animal models of human disease have highlighted TRPM channels as promising new therapeutic targets. Here, we provide an overview of this rapidly evolving research area and delineate the emerging role of TRPM channels in kidney pathophysiology. - Source: PubMed
Publication date: 2023/10/18
Chubanov VladimirKöttgen MichaelTouyz Rhian MGudermann Thomas - The canonical ion channels gated by chemical ligands use the free energy of agonist binding to open the channel pore, returning to a closed state upon agonist departure. A unique class of ion channels, known as channel-enzymes (chanzymes), possess additional enzymatic activity that is directly or indirectly linked to their channel function. Here we investigated a TRPM2 chanzyme from choanoflagellates, an evolutionary ancestor of all metazoan TRPM channels, which integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP ribose (ADPR) with high open probability and an enzyme module (NUDT9-H domain) consuming ADPR at a remarkably slow rate. Using time-resolved cryo- electron microscopy (cryo-EM), we captured a complete series of structural snapshots of the gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. Our results showed that the slow kinetics of the NUDT9-H enzyme module confers a novel self-regulatory mechanism, whereby the enzyme module modulates channel gating in a binary manner. Binding of ADPR to NUDT9-H first triggers tetramerization of the enzyme modules, promoting channel opening, while the subsequent hydrolysis reaction reduces local ADPR availability, inducing channel closure. This coupling enables the ion-conducting pore to alternate rapidly between open and closed states, avoiding Mg and Ca overload. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADPR hydrolase module in early species TRPM2 to a fully integrated component of a gating ring essential for channel activation in advanced species TRPM2. Our study demonstrated an example of how organisms can adapt to their environments at the molecular level. - Source: PubMed
Publication date: 2023/03/20
Huang YiheLü WeiDu Juan