9j84

Structural highlights

Disease

TRPM3_HUMAN Autosomal dominant non-syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.TRPM3_HUMAN Constitutively active, non-selective divalent cation-conducting channel that is permeable to Ca(2+), Mn(2+), and Mg(2+), with a high permeability for Ca(2+). However, can be enhanced by increasing temperature and by ligands, including the endogenous neurosteroid pregnenolone sulfate and sphingosine-1 and suppressed by intracellular Mg(2+) (PubMed:12672799, PubMed:12672827, PubMed:32343227). Implicated in a variety of cellular processes, including insulin/peptide secretion, vascular constriction and dilation, noxious heat sensing, inflammatory and spontaneous pain sensitivity. In neurons of the dorsal root ganglia, functions as thermosensitive channel for the detection of noxious heat and spontaneous pain. Suggested to function as an ionotropic steroid receptor in beta-cell, indeed pregnenolone sulfate leads to Ca(2+) influx and enhanced insulin secretion. Mediates Zn(2+) uptake into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion (By similarity). Forms heteromultimeric ion channels with TRPM1 which are permeable for Ca(2+) and Zn(2+) ions (PubMed:21278253). Exists as multiple splice variants which differ significantly in their biophysical properties (By similarity).[UniProtKB:J9SQF3]^{[1] [2] [3] [4]}

References

1. ↑ Grimm C, Kraft R, Sauerbruch S, Schultz G, Harteneck C. Molecular and functional characterization of the melastatin-related cation channel TRPM3. J Biol Chem. 2003 Jun 13;278(24):21493-501. PMID:12672799 doi:10.1074/jbc.M300945200
2. ↑ Lee N, Chen J, Sun L, Wu S, Gray KR, Rich A, Huang M, Lin JH, Feder JN, Janovitz EB, Levesque PC, Blanar MA. Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3). J Biol Chem. 2003 Jun 6;278(23):20890-7. PMID:12672827 doi:10.1074/jbc.M211232200
3. ↑ Lambert S, Drews A, Rizun O, Wagner TF, Lis A, Mannebach S, Plant S, Portz M, Meissner M, Philipp SE, Oberwinkler J. Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions. J Biol Chem. 2011 Apr 8;286(14):12221-33. PMID:21278253 doi:10.1074/jbc.M110.202945
4. ↑ Zhao S, Yudin Y, Rohacs T. Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms. Elife. 2020 Apr 28;9:e55634. PMID:32343227 doi:10.7554/eLife.55634