TRPML (transient receptor potential cation channel, mucolipin subfamily) comprises a group of three evolutionarily related proteins that belongs to the large family of transient receptor potential ion channels. The three proteins TRPML1, TRPML2 and TRPML3 are encoded by the mucolipin-1 ( MCOLN1 ), mucolipin-2 ( MCOLN2 ) and mucolipin-3 ( MCOLN3 ) genes, respectively.
The three members of the TRPML ("ML" for mucolipin) sub-family are not extremely well characterized. [1] TRPML1 is known to be localized in late endosomes. [2] This subunit also contains a lipase domain between its S1 and S2 segments. While the function of this domain is unknown it has been proposed that it is involved in channel regulation. Physiological studies have described TRPML1 channels as proton leak channels in lysosomes responsible for preventing these organelles from becoming too acidic. [2] TRPML2 and TRPML3 more poorly characterized than TRPML1. [3] [4]
Deficiencies can lead to enlarged vesicles. [5]
Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.
Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation channel, mucolipin1. These mutations disrupt cellular functions and lead to a neurodevelopmental disorder through an unknown mechanism. Researchers dispute the physiological role of the protein product and which ion it transports.
TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.
Mucolipin-1 also known as TRPML1 is a protein that in humans is encoded by the MCOLN1 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.
TRPP is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.
TRPM6 is a transient receptor potential ion channel associated with hypomagnesemia with secondary hypocalcemia.
Transient receptor potential cation channel, subfamily C, member 2, also known as TRPC2, is a protein that in humans is encoded by the TRPC2 pseudogene. This protein is not expressed in humans but is in certain other species such as mouse.
Short transient receptor potential channel 3 (TrpC3) also known as transient receptor protein 3 (TRP-3) is a protein that in humans is encoded by the TRPC3 gene. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy. These are diacylgylcerol-sensitive cation channels known regulate intracellular calcium via activation of the phospholipase C (PLC) pathway and/or by sensing Ca2+ store depletion. Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.
The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.
Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.
Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene.
Transient receptor potential cation channel, subfamily C, member 7, also known as TRPC7, is a human gene encoding a protein of the same name.
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.
Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.
Polycystin-2 is a protein that in humans is encoded by the PKD2 gene.
Mucolipin-2 also known as TRPML2 is a protein that in humans is encoded by the MCOLN2 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.
Mucolipin-3 also known as TRPML3 is a protein that in humans is encoded by the MCOLN3 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.
The Polycystin Cation Channel (PCC) Family consists of several transporters ranging in size from 500 to over 4000 amino acyl residues (aas) in length and exhibiting between 5 and 18 transmembrane segments (TMSs). This family is a constituent of the Voltage-Gated Ion Channel (VIC) Superfamily. These transporters generally catalyze the export of cations. A representative list of proteins belonging to the PCC family can be found in the Transporter Classification Database.
The transient receptor potential Ca2+ channel (TRP-CC) family (TC# 1.A.4) is a member of the voltage-gated ion channel (VIC) superfamily and consists of cation channels conserved from worms to humans. The TRP-CC family also consists of seven subfamilies (TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML) based on their amino acid sequence homology: