MCOLN3
Description
The MCOLN3 (mucolipin TRP cation channel 3) is a protein-coding gene located on chromosome 1.
Mucolipin-3, also known as TRPML3 (transient receptor potential cation channel, mucolipin subfamily, member 3), is a protein encoded by the MCOLN3 gene in humans. It belongs to the TRPML channel family, a subgroup of the larger TRP ion channel family. In humans, the MCOLN3 gene is located on the short arm of chromosome 1 at 1p22.3. It is split into 12 exons, encoding a protein with 553 amino acids and a predicted molecular weight of approximately 64 kDa. Computational analyses suggest the presence of six transmembrane domains, an ion transport motif, and a transient receptor potential motif. The mouse homolog, Mcoln3, is located on the distal end of chromosome 3. Human and mouse TRPML3 proteins share 91% sequence identity. The MCOLN3 gene is present in all vertebrate species with available genomic sequences and has homologs in insects, nematodes, sea urchins, and lower organisms like Hydra and Dictyostelium.
TRPML3 (also known as Mucolipin-3) is a nonselective ligand-gated cation channel that plays a role in regulating membrane trafficking events. It acts as a Ca(2+)-permeable cation channel with inwardly rectifying activity, mediating the release of Ca(2+) from endosomes to the cytoplasm. This contributes to endosomal acidification and is involved in regulating membrane trafficking and fusion within the endosomal pathway. TRPML3 is also permeable to Mg(2+), Na(+), and K(+), but does not appear to function as a mechanosensory transduction channel in inner ear sensory hair cells. It is proposed to have a critical role in the cochlear stereocilia ankle-link region during hair-bundle growth. TRPML3 is involved in regulating autophagy and may contribute to autophagosome formation by providing Ca(2+) for the fusion process through association with GABARAPL2. It may also be involved in various lysosome-dependent cellular events through tissue-specific heteromerization with MCOLN1. Additionally, possible heteromeric ion channel assemblies with TRPV5 demonstrate pharmacological similarities to TRPML3.
MCOLN3 is also known as TRP-ML3, TRPML3.
Associated Diseases
- Griscelli syndrome type 3
- Tietz syndrome
- piebald trait-neurologic defects syndrome
- microcephaly-albinism-digital anomalies syndrome
- Waardenburg syndrome, IIa 2F
- ermine phenotype
- uncombable hair syndrome
- oculocutaneous albinism type 3
- piebaldism
- Waardenburg syndrome type 2A
