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 1809607021  42 ASRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGGKKkVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVR 115
Cdd:cd02208     1 ISVVTLPPGTSSPPHWHPEQDEIFYVLSGEGELTLDDGET-VELKAGDIVLIPPGVPHSFVNTSDEPAVFLVVS 73

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 1809607021  42 ASRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGGKKkVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVR 115
Cdd:cd02208     1 ISVVTLPPGTSSPPHWHPEQDEIFYVLSGEGELTLDDGET-VELKAGDIVLIPPGVPHSFVNTSDEPAVFLVVS 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1809607021  44 RMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVW 111
Cdd:pfam07883   2 LVTLPPGESSPPHRHPGEDEFFYVLEGEGELTVDG--EEVVLKAGDSVYFPAGVPHRFRNTGDEPARL 67

(S)-ureidoglycine aminohydrolase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1809607021  63 TVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVRNGKEPkvvnLEG 127
Cdd:PRK11171   85 TFLFVVEGEITLTLEG--KTHALSEGGYAYLPPGSDWTLRNAGAEDARFHWIRKRYEP----VEG 143

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 1809607021  42 ASRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGGKKkVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVR 115
Cdd:cd02208     1 ISVVTLPPGTSSPPHWHPEQDEIFYVLSGEGELTLDDGET-VELKAGDIVLIPPGVPHSFVNTSDEPAVFLVVS 73

Uncharacterized conserved protein, RmlC-like cupin domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1809607021   1 MPEAKPVLHTPAttlGSSASGAQTDGMLRQNALV--NVCDT-ICASRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVS- 76
Cdd:COG4101     7 DWAHAGVRVVRP---GLDATTAGKQGLDYFEGISaeTVGSTgLWMGLVTIPPGARAKAHHHGEHETAIYVLSGRAETRYg 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1809607021  77 DGGKKKVTLEPGDYALIPAWAEHQEVNESD-EDVVWCIVRNGKEPK--VVNL 125
Cdd:COG4101    84 ERLEHRVVTEPGDFIFIPPGVPHQEINLSDtEPAVAVIARTDPNEQesVVNL 135

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 1809607021  48 KPHTASAIHHHaDEDTVVFAFSGRGTIVSDGGKKKVTlePGDYALIPAWAEHQEVNESDEDVVW-CIV 114
Cdd:cd02222    25 EPGGHTPLHTH-PWEHEVYVLRGKGVVVIGGEEYPVK--PGDVVYIPPNEPHQFRNTGDEPLGFlCIV 89

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1809607021  33 LVNVCDTICASRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVW 111
Cdd:COG0662    20 LGEGGERLSVKRITVPPGAELSLHVHPHRDEFFYVLEGTGEVTIGD--EEVELKAGDSVYIPAGVPHRLRNPGDEPLEL 96

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1809607021  50 HTASAIHhhadedtvvFAFSGRG--TIVsDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVW 111
Cdd:cd02216    39 HTPNALR---------FVLEGPGayTTV-DG--ERCDMEPGDLILTPPGTWHDHGNEGDEPAIW 90

Gentisate 1,2-dioxygenase [Secondary metabolites biosynthesis, transport and catabolism];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1809607021  50 HTASAIHhhadedtvvFAFSGRG--TIVsDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVW 111
Cdd:COG3435    76 HTQSALR---------FVIEGEGayTVV-DG--ERVPMERGDFVLTPSWTWHDHGNEGDEPMIW 127

Pseudomonas aeruginosa PA3510 and related proteins, cupin domain; This family includes bacterial proteins homologous to PA3510, a Pseudomonas aeruginosa protein of unknown function with a beta-barrel fold that belongs to the cupin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1809607021  43 SRMIAKPHTASAIHHHaDEDTVVFAFSGRGTIV--SDGGKKKVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVRNGKEP 120
Cdd:cd02225    56 STMRLPPGQGGALHTH-EVEEVFFVLQGRLTVFweDEGEEHERELGPRDMISVPAGVYRGFKNIGEEDALMQVMLGTGKP 134

                  ...
gi 1809607021 121 KVV 123
Cdd:cd02225   135 GRP 137

Silicibacter pomeroyi SPO2919 and related proteins, uncharacterized sugar phosphate isomerase with a cupin domain; This family includes proteins similar to sugar phosphate isomerase SPO2919 from Silicibacter pomeroyi and Afe_0303 from Acidithiobacillus ferrooxidans, but are as yet uncharacterized. 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 1809607021  49 PHTASAIHH-HADEDTVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAE--HQEVNESDEDVV 110
Cdd:cd02224    26 PGARSSPRHwHSAEEEFVYVLSGEGTLRLDG--EEVLPRPGDFVGFPAGTGvaHQLINRSDEPLV 88

Thermotoga maritima TM1287 decarboxylase, cupin domain; This family includes bacterial proteins homologous to TM1287 decarboxylase, a Thermotoga maritima manganese-containing cupin thought to catalyze the conversion of oxalate to formate and carbon dioxide, due to its similarity to oxalate decarboxylase (OXDC) from Bacillus subtilis. TM1287 shows a cupin fold with a conserved "jelly roll-like" beta-barrel fold and forms a homodimer.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1809607021  43 SRMIAKPHTASAIHHHADEDTVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVV 110
Cdd:cd02221    22 ARVTLPPGSSIGYHQHEGEFEIYYILSGEGLYTDNG--KEYEVKAGDVTFTRDGESHGIENTGDEDLV 87

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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1809607021   54 AIHHHADEDTVVFAFSGRGT--IVSDGGKKKVT--LEPGDYALIPAWAEHQEVNESDEDVVWCIVRNGKEPKVVNLEG 127
Cdd:smart00835  44 PPHYHPRATELLYVVRGEGRvgVVDPNGNKVYDarLREGDVFVVPQGHPHFQVNSGDENLEFVAFNTNDPNRRFFLAG 121

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1809607021  48 KPHTASAIHHHADEDTVVFAFSGRGTiVSDGGKKKvTLEPGDYALIPAWAEHQEVNESDEDVV 110
Cdd:cd06122    35 EPGQSQKVHAHAGSDKVYFVLEGEGR-FTVGDEER-ELGAGEAVLAPAGVPHGVRNTGAERLV 95

7S vicilin seed storage globulin, N-terminal cupin domain; This family contains the N-terminal domains of plant 7S seed storage proteins such as vicilin, and includes beta-conglycinin, phaseolin, canavalin, conglutin-beta, a chromatin protein in Pisum sativum called P54, and a sucrose binding protein in soybean called SBP. These 7S globulins also include soybean allergen beta-conglycinin, peanut allergen conarachin (Ara h 1), walnut allergen Jug r 2, and lentil allergen Len c 1. Proteins in this family perform various functions, including a role in sucrose binding, desiccation, defense against microbes and oxidative stress. The vicilin peptides formed by trypsin or chymotrypsin digestion exhibit antihypertensive effects. These plant seed storage globulins have tandem cupin-like beta-barrel folds (referred to as a bicupin). Storage proteins are the cause of well-known allergic reactions to peanuts and cereals. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1809607021  57 HHADEDTVVFAFSGRGTI--VSDGGKKKVTLEPGDYALIPA 95
Cdd:cd02244    44 HHLDADMVFYVHTGRGTItwVDEDKRESYNLERGDVYRIPA 84

quercetinase, N- and C-terminal cupin domains; This family contains quercetinase (also known as quercetin 2,3-dioxygenase, 2,3QD, QDO and YxaG; EC 1.13.11.24), a mononuclear copper-dependent dioxygenase that catalyzes the cleavage of the flavonol quercetin (5,7,3',4'-tetrahydroxyflavonol) heterocyclic ring to produce 2-protocatechuoyl-phloroglucinol carboxylic acid and carbon monoxide. Bacillus subtilis quercetin 2,3-dioxygenase (QDO) is a homodimer that shows oxygenase activity with several divalent metals such as Mn2+, Co2+, Fe2+, and Cu2+, although the preferred one appears to be Mn2+. The dioxygen binds to the metal ion of the Cu-QDO-quercetin complex, yielding a Cu2+-superoxo quercetin radical intermediate, which then forms a Cu2+-alkylperoxo complex which then evolves into endoperoxide intermediate that decomposes to the product. Quercetinase is a bicupin with two tandem cupin beta-barrel domains, both of which are included in this alignment model. The pirins, which also belong to the cupin domain family, have been shown to catalyze a reaction involving quercetin and may have a function similar to that of quercetinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1809607021  19 ASGAQTDGMLrqnALVnvcdTICASRMIAKPhtasaIHHHADEDTVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPA 95
Cdd:cd02215    23 ATGESTGGAF---TLV----TTEGPKGDAIP-----PHYHKRHHETFYVLEGRLQLWLDG--ESRLLTPGDFASVPP 85

Ureidoglycine aminohydrolase [Nucleotide transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1809607021  63 TVVFAFSGRGTiVSDGGKKKVtLEPGDYALIPAWAEHQEVNESDEDVVWCIVR 115
Cdd:COG3257    83 TFLFVLEGEVT-LTLGGETHE-LTPGGYAYLPPGTPWTLRNAGDEPARFHWIR 133

Homogentisate 1,2-dioxygenase [Secondary metabolites biosynthesis, transport and catabolism];

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1809607021  59 ADEDTVVFAFSGRGTIVSDGGKkkVTLEPGDYALIP 94
Cdd:COG3508   119 ADGDELIFVHEGSGRLETEFGH--LEVEPGDYVVIP 152

(S)-ureidoglycine aminohydrolase and related proteins, N-terminal cupin domain; This family includes the N-terminal cupin domain of (S)-ureidoglycine aminohydrolase (UGlyAH), an enzyme that converts (S)-ureidoglycine into (S)-ureidoglycolate and ammonia, providing the final substrate to the ureide pathway. The ureide pathway has recently been identified as the metabolic route of purine catabolism in plants and some bacteria where, uric acid, which is a major product of the early stage of purine catabolism, is degraded into glyoxylate and ammonia via stepwise reactions by seven different enzymes. Thus, this pathway has a possible physiological role in mobilization of purine ring nitrogen for further assimilation. This enzyme from Arabidopsis thaliana(AtUGlyAH) has been shown to bind a Mn2+ ion, via the C-terminal cupin domain, which acts as a molecular anchor to bind (S)-ureidoglycine, and its binding mode dictates the enantioselectivity of the reaction. The structure of AtUGlyAH shows a bi-cupin fold with a conserved "jelly roll-like" beta-barrel fold and an octameric functional unit. Several structural homologs of UGlyAH, including the Escherichia coli ortholog YlbA (also known as GlxB6), also exhibit similar features.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1809607021  63 TVVFAFSGRGTIVSDGgkKKVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVR-------NGKEPKVV 123
Cdd:cd02211    49 RFLYVLEGEVELTVGG--ETHTLTAGGYAYLPPGTKHSLRNAGDEPARLLWYKkryepleGGAAPEVV 114

Oxalate decarboxylase (OxDC)-like cupin domain; This subfamily contains bacterial and eukaryotic cupin domains of proteins homologous to oxalate decarboxylase (OxDC; EC 4.1.1.2) such as MSMEG_2254, a putative OxDC from Mycobacterium smegmatis. OxDC is a manganese-dependent bicupin that catalyzes the conversion of oxalate to formate and carbon dioxide, utilizing dioxygen as a cofactor. It is evolutionarily related to oxalate oxidase (OxOx or germin; EC 1.2.3.4) which, in contrast, converts oxalate and dioxygen to carbon dioxide and hydrogen peroxide. OxDC is classified as a bicupin because it contains two cupin folds with each domain containing one manganese binding site, with four manganese binding residues (three histidines and one glutamate) conserved as well as a number of hydrophobic residues.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1809607021  49 PHTasaiHHHADEDTVVFAFSGRGTIVSDGGKK-KVTLEPGDYALIPAWAEHQEVNESDEDVVWCIVRNGKEPKVVNL 125
Cdd:cd20306    49 PHW----HPNANELGYVISGEARVSILDPTGSLdTFTVKPGQVVFIPQGWLHWIENVGDEEAHLLIFFNHETPEDIGL 122