XRE (Xenobiotic Response Element) family transcriptional regulators, C-terminal cupin domain; This family contains transcriptional regulators containing an N-terminal XRE (Xenobiotic Response Element) family helix-turn-helix (HTH) DNA-binding domain and a C-terminal cupin domain. Included in this family is Escherichia coli transcription factor SutR (YdcN) that plays a regulatory role in sulfur utilization; it regulates a set of genes involved in the generation of sulfate and its reduction, the synthesis of cysteine, the synthesis of enzymes containing Fe-S as cofactors, and the modification of tRNA with use of sulfur-containing substrates. This family belongs to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  93 GMHVVPLFPFDEKLRFDMLVIELA-AGASSTSSAHEngVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNP 171
Cdd:cd02209     1 GYTYELLSPGLPGRKMEPFLVTLPpGGSGGEPYSHE--GEEFGYVLEGELELTVGGETYVLEAGDSIYFDSDVPHRYRNP 78

                  ....*..
gi 1995340668 172 ADTTARF 178
Cdd:cd02209    79 GDEPARV 85

XRE (Xenobiotic Response Element) family transcriptional regulators, C-terminal cupin domain; This family contains transcriptional regulators containing an N-terminal XRE (Xenobiotic Response Element) family helix-turn-helix (HTH) DNA-binding domain and a C-terminal cupin domain. Included in this family is Escherichia coli transcription factor SutR (YdcN) that plays a regulatory role in sulfur utilization; it regulates a set of genes involved in the generation of sulfate and its reduction, the synthesis of cysteine, the synthesis of enzymes containing Fe-S as cofactors, and the modification of tRNA with use of sulfur-containing substrates. This family belongs to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  93 GMHVVPLFPFDEKLRFDMLVIELA-AGASSTSSAHEngVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNP 171
Cdd:cd02209     1 GYTYELLSPGLPGRKMEPFLVTLPpGGSGGEPYSHE--GEEFGYVLEGELELTVGGETYVLEAGDSIYFDSDVPHRYRNP 78

                  ....*..
gi 1995340668 172 ADTTARF 178
Cdd:cd02209    79 GDEPARV 85

Uncharacterized conserved protein, cupin superfamily [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  85 STFRENEAGMHVVPLFPFDEKLRFDMLVIELAAGASSTSSAHENGVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADR 164
Cdd:COG3837     5 DDLPGPEAGRRYRRLGDALGLTRLGVNLITLPPGASSSPYHAHSAEEEFVYVLEGELTLRIGGEEYVLEPGDSVGFPAGV 84

                          90       100
                  ....*....|....*....|....*
gi 1995340668 165 EHRYHNPADTTARF---HDLIHYPD 186
Cdd:COG3837    85 PHRLRNRGDEPARYlvvGTRAPYPD 109

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1995340668 132 EHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARFHDLI 182
Cdd:pfam07883  21 EFFYVLEGEGELTVDGEEVVLKAGDSVYFPAGVPHRFRNTGDEPARLLDVY 71

Helix-turn-helix XRE-family like proteins;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1995340668   13 LKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNV 62
Cdd:smart00530   2 LKELREEKGLTQEELAEKLGVSRSTLSRIENGKRKPSLETLKKLAKALGV 51

type II toxin-antitoxin system antitoxin HipB;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1995340668   7 RRIGNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNV 62
Cdd:PRK09726   11 TQLANAMKLVRQQNGWTQSELAKKIGIKQATISNFENNPDNTTLTTFFKILQSLEL 66

XRE (Xenobiotic Response Element) family transcriptional regulators, C-terminal cupin domain; This family contains transcriptional regulators containing an N-terminal XRE (Xenobiotic Response Element) family helix-turn-helix (HTH) DNA-binding domain and a C-terminal cupin domain. Included in this family is Escherichia coli transcription factor SutR (YdcN) that plays a regulatory role in sulfur utilization; it regulates a set of genes involved in the generation of sulfate and its reduction, the synthesis of cysteine, the synthesis of enzymes containing Fe-S as cofactors, and the modification of tRNA with use of sulfur-containing substrates. This family belongs to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold capable of homodimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  93 GMHVVPLFPFDEKLRFDMLVIELA-AGASSTSSAHEngVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNP 171
Cdd:cd02209     1 GYTYELLSPGLPGRKMEPFLVTLPpGGSGGEPYSHE--GEEFGYVLEGELELTVGGETYVLEAGDSIYFDSDVPHRYRNP 78

                  ....*..
gi 1995340668 172 ADTTARF 178
Cdd:cd02209    79 GDEPARV 85

Uncharacterized conserved protein, cupin superfamily [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  85 STFRENEAGMHVVPLFPFDEKLRFDMLVIELAAGASSTSSAHENGVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADR 164
Cdd:COG3837     5 DDLPGPEAGRRYRRLGDALGLTRLGVNLITLPPGASSSPYHAHSAEEEFVYVLEGELTLRIGGEEYVLEPGDSVGFPAGV 84

                          90       100
                  ....*....|....*....|....*
gi 1995340668 165 EHRYHNPADTTARF---HDLIHYPD 186
Cdd:COG3837    85 PHRLRNRGDEPARYlvvGTRAPYPD 109

Cupin domain protein related to quercetin dioxygenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  92 AGMHVVPLFPFDEKLRfdmlVIELAAGASSTSSAHENGVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNP 171
Cdd:COG1917     9 TGVSVRVLADGEDELE----VVRVTFEPGARTPWHSHPGEELIYVLEGEGEVEVGGEEYELKPGDVVFIPPGVPHAFRNL 84

                          90
                  ....*....|..
gi 1995340668 172 ADTTARFHDLIH 183
Cdd:COG1917    85 GDEPAVLLVVFS 96

Helix-turn-helix; This large family of DNA binding helix-turn helix proteins includes Cro and CI. Within the protein Swiss:Q5F9C2, the full protein fold incorporates a helix-turn-helix motif, but the function of this member is unlikely to be that of a DNA-binding regulator, the function of most other members, so is not necessarily characteriztic of the whole family.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1995340668  13 LKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNVAFSTF 67
Cdd:pfam01381   1 LKELREELGLSQEELAEKLGVSRSTISKIENGKREPSLETLKKLAEALGVSLDEL 55

DNA-binding transcriptional regulator, XRE-family HTH domain [Transcription];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1995340668   6 TRRIGNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNVAFSTFIEPT 71
Cdd:COG1476     2 KKKLGNRLKELRKERGLTQEELAELLGVSRQTISAIENGKYNPSLELALKIARALGVSLEELFSLE 67

HTH-type transcriptional regulator PuuR;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668   1 MSDElTRRIGNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNVAFST-FIEPTLADE-DVT 78
Cdd:PRK09943    1 MSDE-GLAPGKRLSEIRQQQGLSQRRAAELSGLTHSAISTIEQDKVSPAISTLQKLLKVYGLSLSEfFSEPEKPDEpQVV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  79 YRSGAGSTFRENEAGMHVVplFPFDEKLRFDMLVIELAAGASSTSSAHENGviEHI-IVLEGQLEMTVDGQTHLLSAGDA 157
Cdd:PRK09943   80 INQDDLIEMGSQGVSMKLV--HNGNPNRTLAMIFETYQPGTTTGERIKHQG--EEIgTVLEGEIVLTINGQDYHLVAGQS 155

                         170       180
                  ....*....|....*....|
gi 1995340668 158 LRFAADREHRYHNPADTTAR 177
Cdd:PRK09943  156 YAINTGIPHSFSNTSAGICR 175

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 1995340668 132 EHIIVLEGQLEMTVDGQTHLLSAGDALRFAADRE--HRYHNPADTTARF--------HDLIHYPD 186
Cdd:cd02224    41 EFVYVLSGEGTLRLDGEEVLPRPGDFVGFPAGTGvaHQLINRSDEPLVYlvvgtrlpDDVCTYPD 105

(S)-ureidoglycine aminohydrolase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1995340668 131 IEHII-VLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARFH 179
Cdd:PRK11171   83 AETFLfVVEGEITLTLEGKTHALSEGGYAYLPPGSDWTLRNAGAEDARFH 132

(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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1995340668 131 IEHII-VLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARFH 179
Cdd:cd02211    47 IERFLyVLEGEVELTVGGETHTLTAGGYAYLPPGTKHSLRNAGDEPARLL 96

Predicted transcriptional regulator, contains an XRE-type HTH domain (archaeal members contain CBS pair) [Transcription];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1995340668   8 RIGNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIATGMNVAFSTFI 68
Cdd:COG3620    17 TLGEALRLMRKELGLSQLPVAELVGVSQSDILRIESGKRDPTVSTLEKIAEALGKELSAVL 77

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1995340668 126 HENGVIEHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARF 178
Cdd:cd06988    18 HSHHEYEIFIVISGKGIVVVDGEREPVKAGDVVYIPPGTEHYVKNDGDEDFEF 70

pectin degradation protein KdgF and related proteins, cupin domain; This family includes bacterial and archaeal pectin degradation protein KdgF that catalyzes the linearization of unsaturated uronates from both pectin and alginate, which are polysaccharides found in the cell walls of plants and brown algae, respectively, and represent an important source of carbon. These polysaccharides, mostly consisting of chains of uronates, can be metabolized by bacteria through a pathway of enzymatic steps to the key metabolite 2-keto-3-deoxygluconate (KDG). Pectin degradation is used by many plant-pathogenic bacteria during infection, and also, pectin and alginate can both represent abundant sources of carbohydrate for the production of biofuels. These proteins belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1995340668 135 IVLEGQLEMTVDGQTHLLSAGDALRFAADREH 166
Cdd:cd02238    52 YVLSGRFEFTIGGETRILKPGDSYYIPPNVPH 83

Helix-turn-helix domain; Members of this family contains a DNA-binding helix-turn-helix domain. This family contains many example antitoxins from bacterial toxin-antitoxin systems. These antitoxins are likely to be DNA-binding domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1995340668  10 GNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWKIA 57
Cdd:pfam12844   1 GERLRKAREERGLTQEELAERLGISRSQLSAIENGKSVPPAETLYKIA 48

Phosphomannose isomerase type II, C-terminal cupin domain; This family includes the C-terminal cupin domain of mannose-6-phosphate isomerases (MPIs) which have been classified broadly into two groups, type I and type II, based on domain organization. This family contains type II phosphomannose isomerase (also known as PMI-GDP, phosphomannose isomerase/GDP-D-mannose pyrophosphorylase), a bifunctional enzyme with two domains that catalyze the first and third steps in the GDP-mannose pathway in which fructose 6-phosphate is converted to GDP-D-mannose. The N-terminal domain catalyzes the first and rate-limiting step, the isomerization from D-fructose-6-phosphate to D-mannose-6-phosphate, while the C-terminal cupin domain (represented in this alignment model) converts mannose 1-phosphate to GDP-D-mannose in the final step of the reaction. Although these two domains occur together in one protein in most organisms, they occur as separate proteins in certain cyanobacterial organisms. Also, although type I and type II MPIs have no overall sequence similarity, they share a conserved catalytic motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1995340668 132 EHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARF 178
Cdd:cd02213    63 EHWVVVSGTAEVTLDGKEKLLKEGESIYIPKGTKHRLENPGKIPLEI 109

Helix-turn-helix domain; This domain is a helix-turn-helix domain that probably binds to DNA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1995340668   8 RIGNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGE-SSPTVATL 53
Cdd:pfam13560   1 ELGARLRRLRERAGLSQEALARRLGVSRSTLSRLETGRrGRPSPAVV 47

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
                  ....*....|....*....|....*
gi 1995340668 132 EHIIVLEGQLEMTVDGQTHLLSAGD 156
Cdd:cd02215    55 ETFYVLEGRLQLWLDGESRLLTPGD 79

Desulfitobacterium hafniense dsy2733 and related proteins, cupin domain; This family includes bacterial proteins homologous to dsy2733, a Desulfitobacterium hafniense 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
                  ....*....|....*....|....*....|.
gi 1995340668 136 VLEGQLEMTVDGQTHLLSAGDALRFAADREH 166
Cdd:cd06983    36 VLEGEAEITIGDEKHRLKAGDVLAVPAGVLH 66

transcriptional regulator;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1995340668  10 GNTLKTLRQEKVWSLTRAAEETGVSKAMLGQIERGESSPTVATLWK--------IATGMNV-AFSTFIEPTLADEDVTYR 80
Cdd:PRK04140  128 GDVLREAREELGLSLGELASELGVSRRTISKYENGGMNASIEVAIKleeildvpLTKPIDIlEKVRDDEVTPEDPEEDPF 207

                          90       100
                  ....*....|....*....|....*
gi 1995340668  81 SGAGSTFREnEAGMHVVPLF--PFD 103
Cdd:PRK04140  208 EKEILNVLT-RLGFDVLPTKkaPFD 231

Helicobacter pylori HP0902 and related proteins, cupin domain; This family includes prokaryotic and archaeal proteins homologous to HP0902, a functionally uncharacterized protein from Helicobacter pylori and Spy1581, a protein of unknown function from Streptococcus pyogenes. These proteins demonstrate all-beta cupin folds that cannot bind metal ions due to the absence of a metal-binding histidine that is conserved in many metallo-cupins. HP0902 is able to bind bacterial endotoxin lipopolysaccharides (LPS) through its surface-exposed loops, where metal-binding sites are usually found in other metallo-cupins, and thus may have a putative role in H. pylori pathogenicity.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1995340668 134 IIVLEGQLEMTVDGQTHLLSAGDALRFAADREHR 167
Cdd:cd02230    35 VQVLEGEAEFTIGGETVTLKAGELIVMPANVPHA 68

Bacillus subtilis bacilysin and related proteins, C-terminal cupin domain; This model represents the C-terminal domain of bacilysin (BacB, also known as AerE in Microcystis aeruginosa), a non-ribosomally synthesized dipeptide antibiotic that is produced and excreted by certain strains of Bacillus subtilis. Bacilysin is an oxidase that catalyzes the synthesis of 2-oxo-3-(4-oxocyclohexa-2,5-dienyl)propanoic acid, a precursor to L-anticapsin. Each bacilysin monomer has two tandem cupin domains. It is active against a wide range of bacteria and some fungi. The antimicrobial activity of bacilysin is antagonized by glucosamine and N-acetyl glucosamine, indicating that bacilysin interferes with glucosamine synthesis, and thus, with the synthesis of microbial cell walls. AerE is thought to be involved in the formation of the 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety found on all aeruginosin tetrapeptides, based on gene knock-out experiments. It is encoded by the aerE gene of the aerABCDEF aeruginosin biosynthesis gene cluster in Microcystis aeruginosa. Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" beta-barrel fold.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1995340668 135 IVLEGQLEMTVDGQTHLLSAGDALrFAADRE-HRYHNPADTTAR 177
Cdd:cd10547    44 IILNGKYDMTVGGEEQELGYGKIY-YAPPNVsHSGYNDSDETAT 86

Ethanolamine utilization protein EutQ, cupin superfamily (function unknown) [Amino acid transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1995340668 132 EHIIVLEGQLEMTVDGQTHLLSAGDALRFAADREHRYHNPADTTARFhdlIHYP 185
Cdd:COG4766    69 EVDYVLEGTLTIEIDGETVTAGPGDVIYIPKGSSITFSTPEKARFFY---VTYP 119