Recombinant Human Lens fiber major intrinsic protein (MIP) Protein

Function

Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient (PubMed:11001937, PubMed:24120416). Specifically expressed in lens fiber cells, this aquaporin is crucial for maintaining lens water homeostasis and transparency. Beyond water permeability, it also acts as a cell-to-cell adhesion molecule, forming thin junctions between lens fiber cells that are essential for maintaining the ordered structure and transparency of the lens (PubMed:24120416)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Cell junction

Disease Association

Cataract 15, multiple types (CTRCT15) : An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT15 includes polymorphic, progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical, among others. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in the cortex and nucleus of the retina lens (at protein level) (PubMed:30790544). Major component of lens fiber gap junctions (PubMed:24120416)

Subunit

Homotetramer; each monomer provides an independent water pore. Two homotetramers on opposing membranes can dimerize, forming a cell-cell junction (By similarity). Interacts with CALM; the calcium-calmodulin/CALM complex interacts with the cytoplasmic domains of two aquaporins, leading to channel closure (By similarity). Interacts with BFSP1 (via C-terminus); prevents calcium-dependent inhibition of the water channel activity (PubMed:30790544)

• Pisano M.M. et al. Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens. — Genomics (1991)
• Scherer S.E. et al. The finished DNA sequence of human chromosome 12. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Schey K.L. et al. Characterization of human lens major intrinsic protein structure. — Invest. Ophthalmol. Vis. Sci. (2000)
• Berry V. et al. Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q. — Nat. Genet. (2000)
• Geyer D.D. et al. Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract. — Am. J. Ophthalmol. (2006)
• Ismail V.S. et al. The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes. — Biochim. Biophys. Acta (2016)
• Tapodi A. et al. BFSP1 C-terminal domains released by post-translational processing events can alter significantly the calcium regulation of AQP0 water permeability. — Exp. Eye Res. (2019)