gentisate 1,2-dioxygenase, 1-hydroxy-2-naphthoate dioxygenase, and salicylate 1,2-dioxygenase, N-terminal cupin domain; This family includes the N-terminal cupin domains of three closely related bicupin aromatic ring-cleaving dioxygenases: gentisate 1,2-dioxygenase (GDO), salicylate 1,2-dioxygenase (SDO), and 1-hydroxy-2-naphthoate dioxygenase (NDO). GDO catalyzes the cleavage of the gentisate (2,5-dihydroxybenzoate) aromatic ring, a key step in the gentisate degradation pathway allowing soil bacteria to utilize 2,5-xylenol, 3,5-xylenol, and m-cresol as sole carbon and energy sources. NDO catalyzes the cleavage of 1-hydroxy-2-naphthoate as part of the bacterial phenanthrene degradation pathway. SDO is a ring cleavage dioxygenase from Pseudaminobacter salicylatoxidans that oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid via a novel ring fission mechanism. SDO differs from other known GDOs and NDOs in its unique ability to oxidatively cleave many different salicylate, gentisate and 1-hydroxy-2-naphthoate substrates with high catalytic efficiency. The active site of these enzymes is located in the N-terminal domain but could be influenced by changes in the C-terminal domain, which lacks the strictly conserved metal-binding residues found in other cupin domains and is thought to be an inactive vestigial remnant.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148503458   8 RRVLVLANPGLGlENMQATPTIYVGMQLIMPGETAPNHRHTPSAVRFVVEGEGAATIVNGEVCPMEKGDLILTPPGLWHQ 87
Cdd:cd02216    1 RRVLLLVNPGLP-GTRATTHTLYAGLQLLPPGEVAPAHRHTPNALRFVLEGPGAYTTVDGERCDMEPGDLILTPPGTWHD 79

                         90       100
                 ....*....|....*....|....*..
gi 148503458  88 HEHNGTGPVIWLDALDLPLVYALEASY 114
Cdd:cd02216   80 HGNEGDEPAIWLDGLDAPLVTYLRASF 106

Cupin; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148503458    45 HRHT-PSAVRFVVEGEGAATIVNGEVC-----PMEKGDLILTPPGLWHQHEHNGTGPVIWL 99
Cdd:smart00835  46 HYHPrATELLYVVRGEGRVGVVDPNGNkvydaRLREGDVFVVPQGHPHFQVNSGDENLEFV 106

gentisate 1,2-dioxygenase, 1-hydroxy-2-naphthoate dioxygenase, and salicylate 1,2-dioxygenase, N-terminal cupin domain; This family includes the N-terminal cupin domains of three closely related bicupin aromatic ring-cleaving dioxygenases: gentisate 1,2-dioxygenase (GDO), salicylate 1,2-dioxygenase (SDO), and 1-hydroxy-2-naphthoate dioxygenase (NDO). GDO catalyzes the cleavage of the gentisate (2,5-dihydroxybenzoate) aromatic ring, a key step in the gentisate degradation pathway allowing soil bacteria to utilize 2,5-xylenol, 3,5-xylenol, and m-cresol as sole carbon and energy sources. NDO catalyzes the cleavage of 1-hydroxy-2-naphthoate as part of the bacterial phenanthrene degradation pathway. SDO is a ring cleavage dioxygenase from Pseudaminobacter salicylatoxidans that oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid via a novel ring fission mechanism. SDO differs from other known GDOs and NDOs in its unique ability to oxidatively cleave many different salicylate, gentisate and 1-hydroxy-2-naphthoate substrates with high catalytic efficiency. The active site of these enzymes is located in the N-terminal domain but could be influenced by changes in the C-terminal domain, which lacks the strictly conserved metal-binding residues found in other cupin domains and is thought to be an inactive vestigial remnant.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148503458   8 RRVLVLANPGLGlENMQATPTIYVGMQLIMPGETAPNHRHTPSAVRFVVEGEGAATIVNGEVCPMEKGDLILTPPGLWHQ 87
Cdd:cd02216    1 RRVLLLVNPGLP-GTRATTHTLYAGLQLLPPGEVAPAHRHTPNALRFVLEGPGAYTTVDGERCDMEPGDLILTPPGTWHD 79

                         90       100
                 ....*....|....*....|....*..
gi 148503458  88 HEHNGTGPVIWLDALDLPLVYALEASY 114
Cdd:cd02216   80 HGNEGDEPAIWLDGLDAPLVTYLRASF 106

Cupin domain; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148503458   32 GMQLIMPGETAPNHRHTPS-AVRFVVEGEGAATiVNGEVCPMEKGDLILTPPGLWHQHEHNGTGPVIWLD 100
Cdd:pfam07883   1 GLVTLPPGESSPPHRHPGEdEFFYVLEGEGELT-VDGEEVVLKAGDSVYFPAGVPHRFRNTGDEPARLLD 69

RmlC-like cupin superfamily; This superfamily contains proteins similar to the RmlC (dTDP (deoxythymidine diphosphates)-4-dehydrorhamnose 3,5-epimerase)-like cupins. RmlC is a dTDP-sugar isomerase involved in the synthesis of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. Cupins are a functionally diverse superfamily originally discovered based on the highly conserved motif found in germin and germin-like proteins. This conserved motif forms a beta-barrel fold found in all of the cupins, giving rise to the name cupin ('cupa' is the Latin term for small barrel). The active site of members of this superfamily is generally located at the center of a conserved barrel and usually includes a metal ion. The different functional classes in this superfamily include single domain bacterial isomerases and epimerases involved in the modification of cell wall carbohydrates, two domain bicupins such as the desiccation-tolerant seed storage globulins, and multidomain nuclear transcription factors involved in legume root nodulation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148503458  31 VGMQLIMPGETAPNHRHTPSA-VRFVVEGEGAATIVNGEVCPMEKGDLILTPPGLWHQHEHNGTGPVIWL 99
Cdd:cd02208    1 ISVVTLPPGTSSPPHWHPEQDeIFYVLSGEGELTLDDGETVELKAGDIVLIPPGVPHSFVNTSDEPAVFL 70

Mannose-6-phosphate isomerase, cupin superfamily [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 148503458  24 QATPTIYVGMQLIMPGETAPNHRHTPSA-VRFVVEGEGAATIvNGEVCPMEKGDLILTPPGLWHQHEHNGTGPVIWL 99
Cdd:COG0662   22 EGGERLSVKRITVPPGAELSLHVHPHRDeFFYVLEGTGEVTI-GDEEVELKAGDSVYIPAGVPHRLRNPGDEPLELL 97

Thermotoga maritima TM1459 and related proteins, cupin domain; This family includes bacterial and archaeal proteins homologous to Thermotoga maritima TM1459, a manganese-containing cupin that has been shown to cleave C=C bonds in the presence of alkylperoxide as oxidant in vitro. Its biological function is still unknown. This family also includes Halorhodospira halophila Hhal_0468. Structures of these proteins show a cupin fold with a conserved "jelly roll-like" beta-barrel fold that form a homodimer.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148503458  36 IMPGETAPNHRHT-PSAVrFVVEGEGAATIvNGEVCPMEKGDLILTPPGLWHQHEHNGTGP 95
Cdd:cd02222   24 IEPGGHTPLHTHPwEHEV-YVLRGKGVVVI-GGEEYPVKPGDVVYIPPNEPHQFRNTGDEP 82

Microcystis aeruginosa MAE_RS03005 and related proteins, cupin domain; This family includes bacterial and some eukaryotic proteins homologous to MAE_RS03005, a Microcystis aeruginosa protein of unknown function. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 148503458  38 PGETAPNHRHtPSAVR--FVVEGEGAATiVNGEVCPMEKGDLILTPPGLWHQHEHNGTG 94
Cdd:cd06987   37 PGGRTPPNTH-PAAHEmfFVLAGEGRAY-CDGQRVPLRPGDALVVPPGSEHVIENTGSG 93

Dimethylsulfoniopropionate lyase DddK and related proteins, cupin domain; This family includes mostly bacterial proteins homologous to dimethylsulfoniopropionate lyase DddK from marine bacterium Pelagibacter. DddK cleaves dimethylsulfoniopropionate (DMSP), the organic osmolyte and antioxidant produced in marine environments, and yields acrylate and the climate-active gas dimethyl sulfide (DMS). DddK contains a double-stranded beta-helical motif which utilizes various divalent metal ions as cofactors for catalytic activity; however, nickel, an abundant metal ion in marine environments, confers the highest DMSP lyase activity. Also included in this family is Plu4264, a Photorhabdus luminescens manganese-containing cupin shown to have similar metal binding site to TM1287 decarboxylase, but two very different substrate binding pockets. The Plu4264 binding pocket shows a cavity and substrate entry point more than twice as large as and more hydrophobic than TM1287, suggesting that Plu4264 accepts a substrate that is significantly larger than that of TM1287, a putative oxalate decarboxylase. Thus, the function of Plu4264 could be similar to that of TM1287 but with a larger, less charged substrate. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148503458  36 IMPGETAPNHRHTPSAVRFVVEGEGAATiVNGEVCPMEKGDLILTPPGLWHQHEHNGTGP----VIWLD 100
Cdd:cd06988    9 VRPGTTSTPHSHHEYEIFIVISGKGIVV-VDGEREPVKAGDVVYIPPGTEHYVKNDGDEDfefySIWWD 76

Cupin; This family represents the conserved barrel domain of the 'cupin' superfamily ('cupa' is the Latin term for a small barrel). This family contains 11S and 7S plant seed storage proteins, and germins. Plant seed storage proteins provide the major nitrogen source for the developing plant.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 148503458    45 HRHT-PSAVRFVVEGEGAATIVNGEVC-----PMEKGDLILTPPGLWHQHEHNGTGPVIWL 99
Cdd:smart00835  46 HYHPrATELLYVVRGEGRVGVVDPNGNkvydaRLREGDVFVVPQGHPHFQVNSGDENLEFV 106

Thermus thermophilus TTHA0104 and related proteins, cupin domain; This family contains bacterial proteins including TTHA0104 (also called TT1209), a putative antibiotic synthesis protein from Thermus thermophilus. TTHA0104 is a cupin-like protein. The cupins are a functionally diverse superfamily originally discovered based on the highly conserved motif found in germin and germin-like proteins. This conserved motif forms a beta-barrel fold found in all of the cupins, giving rise to the name cupin (cupa is the Latin term for small barrel).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 148503458  26 TPTIYVGMQLIMPGETAPNHRHTPSA-VRFVVEGEGAATiVNGEVCPMEKGDLILTPPGLWHQHEHNGTGPVIWL 99
Cdd:cd06122   24 SERLFCDLYCLEPGQSQKVHAHAGSDkVYFVLEGEGRFT-VGDEERELGAGEAVLAPAGVPHGVRNTGAERLVLL 97

Bacillus halodurans Bh2720 and related proteins, cupin domain; This family includes bacterial, archaeal, and eukaryotic proteins similar to Bh2720, a Bacillus halodurans protein of unknown function with a cupin beta-barrel fold.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 148503458  54 FVVEGEGAAtIVNGEVCPMEKGDLILTPPGLWHQ 87
Cdd:cd02223   37 RIEEGEGKA-IMGGFESEVKDGDAIIVPAGTWHN 69

AraC/XylS family transcriptional regulators similar to MmsR, N-terminal cupin domain; This family contains bacterial proteins containing an AraC/XylS family helix-turn-helix (HTH) DNA-binding domain C-terminal to a cupin domain, and may be possible transcriptional regulators. Included is MmsR, a bacterial transcriptional regulator thought to positively regulate the expression of the mmsAB operon. The mmsAB operon contains two structural genes involved in valine metabolism: mmsA which encodes methylmalonate-semialdehyde dehydrogenase, and mmsB which encodes 3-hydroxyisobutyrate dehydrogenase. The cupin domain of members of this subfamily does not contain a metal binding site.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 148503458  40 ETAPNHRHTPsAVR------FVVEGEGAATIvNGEVCPMEKGDLILTPPG 83
Cdd:cd06986   14 PCEPGHSYGP-AVRdyyilhYVLSGKGTFSV-NGKTYHLKAGQGFLIPPG 61