PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817 368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSW 447
Cdd:cd01752   1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 15620817 448 YVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA 487
Cdd:cd01752  81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTFPVA 120

PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817 368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSW 447
Cdd:cd01752   1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 15620817 448 YVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA 487
Cdd:cd01752  81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTFPVA 120

Lipoxygenase homology 2 (beta barrel) domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817    368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNsgDRPSW 447
Cdd:smart00308   1 GKYKVTVTTGGLDFAGTTASVSLSLVGAEGDGKESKLDYLFKGIFARGSTYEFTFDVDEDFGELGAVKIKNEH--RHPEW 78

                           90       100
                   ....*....|....*....|....*
gi 15620817    448 YVSRVLVYDLVMDRKWYFLCNSWLS 472
Cdd:smart00308  79 FLKSITVKDLPTGGKYHFPCNSWVY 103

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 15620817   259 HCVFWDEVQET---WDDSGCQVGPRTSpYQTHCLCNHLTFFG 297
Cdd:pfam01825   2 QCVFWDFTNSTtgrWSTEGCTTVSLND-THTVCSCNHLTSFA 42

PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817 368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSW 447
Cdd:cd01752   1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 15620817 448 YVSRVLVYDLVMDRKWYFLCNSWLSINVGDCVLDKVFPVA 487
Cdd:cd01752  81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTFPVA 120

PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or LH2 (Lipoxygenase homology 2) domain. It consists of an eight stranded beta-barrel. The domain can be found in various domain architectures, in case of lipoxygenases, alpha toxin, lipases and polycystin, but also as a single domain or as repeats.The putative function of this domain is to facilitate access to sequestered membrane or micelle bound substrates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817 368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPH-HLADPDTpvFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPS 446
Cdd:cd00113   1 CRYTVTIKTGDKKGAGTDSNISLALYGENGNSSDIpILDGPGS--FERGSTDTFQIDLKLDIGDITKVYLRRDGSGLSDG 78

                        90       100
                ....*....|....*....|....*.
gi 15620817 447 WYVSRVLVYDLVMDRKWYFLCNSWLS 472
Cdd:cd00113  79 WYCESITVQALGTKKVYTFPVNRWVL 104

Lipoxygenase homology 2 (beta barrel) domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817    368 YHYLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPDTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNsgDRPSW 447
Cdd:smart00308   1 GKYKVTVTTGGLDFAGTTASVSLSLVGAEGDGKESKLDYLFKGIFARGSTYEFTFDVDEDFGELGAVKIKNEH--RHPEW 78

                           90       100
                   ....*....|....*....|....*
gi 15620817    448 YVSRVLVYDLVMDRKWYFLCNSWLS 472
Cdd:smart00308  79 FLKSITVKDLPTGGKYHFPCNSWVY 103

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 15620817   259 HCVFWDEVQET---WDDSGCQVGPRTSpYQTHCLCNHLTFFG 297
Cdd:pfam01825   2 QCVFWDFTNSTtgrWSTEGCTTVSLND-THTVCSCNHLTSFA 42

PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and plasma lipoproteins. Both types of enzymes are cytosolic but need this domain to access their sequestered membrane or micelle bound substrates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15620817 370 YLVTVYTGHRRGAATSSKVTVTLYGLDGEREPHHLADPdTPVFERGAVDAFLLSTLFPLGELRSLRLWHDNSGDRPSWYV 449
Cdd:cd01753   3 YKVTVATGSSLFAGTDDYIYLTLVGTAGESEKQLLDRP-GYDFERGAVDEYKVKVPEDLGELLLVRLRKRKYLLFDAWFC 81

                        90       100       110
                ....*....|....*....|....*....|.
gi 15620817 450 SRVLVYDLVMDRKWyFLCNSWLsinVGDCVL 480
Cdd:cd01753  82 NYITVTGPGGDEYH-FPCYRWI---EGYGTL 108