This is the Kringle-like domain (KLD) found in Melanocyte protein PMEL, Transmembrane glycoprotein NMB (GPNMB) and Transmembrane protein 130 (TMEM130), which is downstream the PKD domain. It contains six highly conserved cysteine residues that form the disulphide bonds of mature PMEL dimers and promotes PMEL functional amyloid formation [, ]. This domain is perfectly conserved in PMEL and GPNMB which suggests that GPNMB also forms dimers. PMEL and GPNMB, together with TMEM130 (its most ancient paralogue), have a conserved domain architecture and have been recently described as the PKAT (PKD- and KLD-Associated Transmembrane) protein family []. PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.
This family includes Melanocyte protein PMEL (also known as PMEL-17), Transmembrane glycoprotein NMB (GPNMB) and Transmembrane protein 130, previously described as melanocyte protein PMEL-17-related family. Regarding the highly conserved domain architecture of these family members, including the PKD, KLD and transmembrane (TM) domains, the name was updated and now referred to as PKD- and KLD-Associated Transmembrane (PKAT) protein family []. TMEM130 has been identified as the most ancient paralogue of PMEL and GPNMB.PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.