PKAT, KLD domain; This is the Kringle-like domain (KLD) found in Melanocyte protein PMEL, Transmembrane glycoprotein NMB (GPNMB) and TMEM130, which is downstream the PKD domain. It contains six highly conserved cysteine residues that form the disulphide bonds of mature PMEL dimers. (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). 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 (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1019366880 407 TCQGSFPTDVCTAVSDPTCQVSQGMVCDPVVVTDECVLTIRRAFDEPGTYC 457
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

PKAT, KLD domain; This is the Kringle-like domain (KLD) found in Melanocyte protein PMEL, Transmembrane glycoprotein NMB (GPNMB) and TMEM130, which is downstream the PKD domain. It contains six highly conserved cysteine residues that form the disulphide bonds of mature PMEL dimers. (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). 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 (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1019366880 407 TCQGSFPTDVCTAVSDPTCQVSQGMVCDPVVVTDECVLTIRRAFDEPGTYC 457
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an IG-like fold; domain probably functions as a ligand binding site in protein-protein or protein-carbohydrate interactions; a single instance of the repeat is presented here. The domain is also found in microbial collagenases and chitinases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1019366880 259 PITFDVKIHDPSyylNDSAISYKWNFGDGSGlFVESGATTSHTFSLQGNFTLNLTVQ 315
Cdd:cd00146    14 GASVTFSASDSS---GGSIVSYKWDFGDGEV-SSSGEPTVTHTYTKPGTYTVTLTVT 66

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1019366880  219 YVPIARASTTYV-VTDKIPILV-SMSQKHDRNISDSIFIKDSPITFDVkiHD-PSYYlndsAISYKWNFGDGSGLFVESG 295
Cdd:TIGR00864 1062 YLATVLASNAFEnISQQINMSVrAILPRVAIGTEDGLLLAGKPADFEA--HPlPSPG----GIHYEWDFGDGSALLQGRQ 1135

                           90       100
                   ....*....|....*....|...
gi 1019366880  296 ATTSHTFSLQGNFTLNLTVQAII 318
Cdd:TIGR00864 1136 PAAAHTFAKRGPFHVCLEVNNTI 1158

PKAT, KLD domain; This is the Kringle-like domain (KLD) found in Melanocyte protein PMEL, Transmembrane glycoprotein NMB (GPNMB) and TMEM130, which is downstream the PKD domain. It contains six highly conserved cysteine residues that form the disulphide bonds of mature PMEL dimers. (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). 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 (Chrystal et. al., Molecules 2021, 26(12), 3529; https://doi.org/10.3390/molecules26123529). PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1019366880 407 TCQGSFPTDVCTAVSDPTCQVSQGMVCDPVVVTDECVLTIRRAFDEPGTYC 457
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an IG-like fold; domain probably functions as a ligand binding site in protein-protein or protein-carbohydrate interactions; a single instance of the repeat is presented here. The domain is also found in microbial collagenases and chitinases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1019366880 259 PITFDVKIHDPSyylNDSAISYKWNFGDGSGlFVESGATTSHTFSLQGNFTLNLTVQ 315
Cdd:cd00146    14 GASVTFSASDSS---GGSIVSYKWDFGDGEV-SSSGEPTVTHTYTKPGTYTVTLTVT 66

PKD domain; This domain was first identified in the Polycystic kidney disease protein PKD1. This domain has been predicted to contain an Ig-like fold.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1019366880 276 SAISYKWNFGDGSGLfVESGATTSHTFSLQGNFTLNLTV 314
Cdd:pfam00801  24 SNVTYTWDFGDSPGT-SGSGPTVTHTYLSPGTYTVTLTA 61