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 528518510  467 SCQGSIPTEVCTIVSDADCHAPVMTICNAVSPSSDCQLILRHFFNDSGTFC 517
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

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 528518510   125 VSPNAHLFSRQG---DKPPPYVFVWKTW-GKYWQVCDGP--SSSLTIdTDDVPLGSYIMDVVIYHYRQKDRFIPIGFAST 198
Cdd:TIGR00864  992 LPPGATLALTAGvliDMAVEAAFLWSFGdGEQALFEFKPpyNESFPC-PDPSPAQVLLEHNVMHIYAAPGEYLATVLASN 1070

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528518510   199 QF-SIIDQIPFAV--SLTQVnDKDQGDHKFVQNRAVAFsitlhDPSEYLSKSDVTFNWNFGDGSGTVISRESTVTHTYIA 275
Cdd:TIGR00864 1071 AFeNISQQINMSVraILPRV-AIGTEDGLLLAGKPADF-----EAHPLPSPGGIHYEWDFGDGSALLQGRQPAAAHTFAK 1144

                          170
                   ....*....|....
gi 528518510   276 SGVFKPQVVVQAAI 289
Cdd:TIGR00864 1145 RGPFHVCLEVNNTI 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 528518510  467 SCQGSIPTEVCTIVSDADCHAPVMTICNAVSPSSDCQLILRHFFNDSGTFC 517
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 protein contains 14 repeats, present elsewhere such as in microbial collagenases.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 528518510   231 VAFSITLHDPSEYlSKSDVTFNWNFGDGSgtvISRESTVTHTYIASGVFKPQVVVQAAI 289
Cdd:smart00089  13 AGESVTFTATSSD-DGSIVSYTWDFGDGT---SSTGPTVTHTYTKPGTYTVTLTVTNAV 67

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 528518510 233 FSITLHDPSeylSKSDVTFNWNFGDGSGTViSRESTVTHTYIASGVFKPQVVVQAA 288
Cdd:cd00146   17 VTFSASDSS---GGSIVSYKWDFGDGEVSS-SGEPTVTHTYTKPGTYTVTLTVTNA 68

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 528518510  467 SCQGSIPTEVCTIVSDADCHAPVMTICNAVSPSSDCQLILRHFFNDSGTFC 517
Cdd:pfam20433   1 TCQGSLPTEVCTVVSDPTCQTPQNTVCNPVSPSPECQLVLRRAFNGSGTYC 51

Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 protein contains 14 repeats, present elsewhere such as in microbial collagenases.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 528518510   231 VAFSITLHDPSEYlSKSDVTFNWNFGDGSgtvISRESTVTHTYIASGVFKPQVVVQAAI 289
Cdd:smart00089  13 AGESVTFTATSSD-DGSIVSYTWDFGDGT---SSTGPTVTHTYTKPGTYTVTLTVTNAV 67

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 528518510 233 FSITLHDPSeylSKSDVTFNWNFGDGSGTViSRESTVTHTYIASGVFKPQVVVQAA 288
Cdd:cd00146   17 VTFSASDSS---GGSIVSYKWDFGDGEVSS-SGEPTVTHTYTKPGTYTVTLTVTNA 68