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.
The polycystic kidney disease (PKD) domain is an 80-90 amino acid module originally found in 16 copies in the extracellular segment of polycystin-1, a large cell surface glycoprotein. Polycystin-1 is encoded by the PKD1 gene, which is mutated in autosomal dominant polycystic kidney disease (ADPKD).Although its function is unknown, it may be involved in protein-protein and protein-carbohydrate interactions based on its predicted domain structure. One or more copies of the PKD domain are also found in several other extracellular proteins from higher organisms, eubacteria, and archaebacteria. Singles copies of the PKD domain are found in the melanocytes heavily glycosylated cell-surface proteins Pmel 17, MMP and Nmp. Some bacterial collagenases and proteases also contain a single PKD domain adjacent to their catalytic domains, whereas four copies are present in the heavily glycosylated surface layer protein of archaebacteria []. The PKD modules are often observed, within a same protein sequence, in association with FnIII domains [].The most conserved motif is the WDFGDGS sequence that is found in the central part of many PKD domains and could play a structural role [, ]. Determination of the solution structure of the first PKD domain from human polycystin-1 has shown that the module is built from two β-sheet, one of three strands and one of four strands, which are packed face-to-face [].
The polycystic kidney disease (PKD) domain is an 80-90 amino acid module originally found in 16 copies in the extracellular segment of polycystin-1, a large cell surface glycoprotein. Polycystin-1 is encoded by the PKD1 gene, which is mutated in autosomal dominant polycystic kidney disease (ADPKD).Although its function is unknown, it may be involved in protein-protein and protein-carbohydrate interactions based on its predicted domain structure. One or more copies of the PKD domain are also found in several other extracellular proteins from higher organisms, eubacteria, and archaebacteria. Singles copies of the PKD domain are found in the melanocytes heavily glycosylated cell-surface proteins Pmel 17, MMP and Nmp. Some bacterial collagenases and proteases also contain a single PKD domain adjacent to their catalytic domains, whereas four copies are present in the heavily glycosylated surface layer protein of archaebacteria []. The PKD modules are often observed, within a same protein sequence, in association with FnIII domains [].The most conserved motif is the WDFGDGS sequence that is found in the central part of many PKD domains and could play a structural role [, ]. Determination of the solution structure of the first PKD domain from human polycystin-1 has shown that the module is built from two β-sheet, one of three strands and one of four strands, which are packed face-to-face [].
