MCOLN1

Last updated
MCOLN1
Identifiers
Aliases MCOLN1 , MG-2, ML4, MLIV, MST080, MSTP080, TRP-ML1, TRPM-L1, TRPML1, mucolipin 1, ML1, mucolipin TRP cation channel 1
External IDs OMIM: 605248; MGI: 1890498; HomoloGene: 10744; GeneCards: MCOLN1; OMA:MCOLN1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_020533

NM_053177

RefSeq (protein)

NP_065394

NP_444407

Location (UCSC) Chr 19: 7.52 – 7.53 Mb Chr 8: 3.55 – 3.57 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mucolipin-1(ML1) also known as TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) is a protein that in humans is encoded by the MCOLN1 gene. [5] It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

Contents

TRPML1 is a 65 kDa protein associated with mucolipidosis type IV. Its predicted structure includes six transmembrane domains, a transient receptor potential (TRP) cation-channel domain, and an internal channel pore. [6] TRPML1 is believed to channel iron ions across the endosome/lysosome membrane into the cell and so its malfunction causes cellular iron deficiency. [7] It is important in lysosome function and plays a part in processes such as vesicular trafficking, exocytosis and autophagy. [8] [9]

Ligands

Agonists

See also

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

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 taste, 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.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

<span class="mw-page-title-main">TRPA (ion channel)</span> Family of transport proteins

TRPA is a family of transient receptor potential ion channels. The TRPA family is made up of 7 subfamilies: TRPA1, TRPA- or TRPA1-like, TRPA5, painless, pyrexia, waterwitch, and HsTRPA. TRPA1 is the only subfamily widely expressed across animals, while the other subfamilies are largely absent in deuterostomes.

<span class="mw-page-title-main">TRPC6</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a protein encoded in the human by the TRPC6 gene. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily.

<span class="mw-page-title-main">TRPC1</span> Protein and coding gene in humans

Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the TRPC1 gene.

<span class="mw-page-title-main">TRPC4</span> Protein and coding gene in humans

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.

<span class="mw-page-title-main">TRPC5</span> Protein-coding gene in the species Homo sapiens

Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.

<span class="mw-page-title-main">TRPM2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TRPV2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

<span class="mw-page-title-main">TRPM4</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TRPM3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

<span class="mw-page-title-main">TRPV3</span> Protein-coding gene in humans

Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.

<span class="mw-page-title-main">TRPM7</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name.

<span class="mw-page-title-main">MCOLN2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">MCOLN3</span> Protein-coding gene in the species Homo sapiens

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 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:

  1. the canonical or classic TRPs,
  2. the vanilloid receptor TRPs,
  3. the melastatin or long TRPs,
  4. ankyrin (whose only member is the transmembrane protein 1 [TRPA1])
  5. TRPN after the nonmechanoreceptor potential C (nonpC), and the more distant cousins,
  6. the polycystins
  7. and mucolipins.
<span class="mw-page-title-main">MK6-83</span> Chemical compound

MK6-83 is a chemical compound which acts as a channel opener for the TRPML family of calcium channels, with moderate selectivity for TRPML1 over the related TRPML2 and TRPML3 subtypes.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000090674 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004567 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID   16382100. S2CID   17936350.
  6. Venugopal B, Browning MF, Curcio-Morelli C, Varro A, Michaud N, Nanthakumar N, Walkley SU, Pickel J, Slaugenhaupt SA (November 2007). "Neurologic, gastric, and opthalmologic[sic] pathologies in a murine model of mucolipidosis type IV". Am. J. Hum. Genet. 81 (5): 1070–83. doi:10.1086/521954. PMC   2265643 . PMID   17924347.
  7. Dong X, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H (2008). "The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel". Nature. 455 (7215): 992–6. Bibcode:2008Natur.455..992D. doi:10.1038/nature07311. PMC   4301259 . PMID   18794901.
  8. Wang W, Zhang X, Gao Q, Xu H (2014). "TRPML1: an ion channel in the lysosome". Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology. Vol. 222. pp. 631–45. doi:10.1007/978-3-642-54215-2_24. ISBN   978-3-642-54214-5. PMID   24756723.
  9. Di Paola S, Scotto-Rosato A, Medina DL (January 2018). "TRPML1: The Ca(2+)retaker of the lysosome". Cell Calcium. 69: 112–121. doi:10.1016/j.ceca.2017.06.006. PMID   28689729.
  10. Schmiege P, Fine M, Blobel G, Li X (October 2017). "Human TRPML1 channel structures in open and closed conformations". Nature. 550 (7676): 366–370. Bibcode:2017Natur.550..366S. doi:10.1038/nature24036. PMC   5920536 . PMID   29019983.