SII-SWORD/CoKE huggingface dataset:
Fe-S hydro-lyase, tartrate dehydratase beta-type, catalytic domain (Fe-S_hydro-lyase_TtdB-typ_cat)
Type: Domain

This entry represents various Fe-S type hydro-lyases, including the beta subunit from both L-tartrate dehydratase (TtdB;

) and class 2 fumarate hydratase (FumC;

) . A number of Fe-S cluster-containing hydro-lyases share a conserved motif, including argininosuccinate lyase, adenylosuccinate lyase, aspartase, class I fumarate hydratase (fumarase), and tartrate dehydratase (see

). Proteins in this group represent a subset of closely related proteins or modules, including the Escherichia coli tartrate dehydratase beta chain and the C-terminal region of the class I fumarase (where the N-terminal region is homologous to the tartrate dehydratase alpha chain). The activity of the archaeal proteins in this group is unknown.
Tetrapeptide transporter, OPT1/isp4 (Oligpept_transpt)
Type: Family

Oligopeptide transporter OPT superfamily has two main branches. One branch contains a tetrapeptide transporter demonstrated experimentally in three different species of yeast. The other family contains EspB, a protein required for normal rather than delayed sporulation after cellular aggregation; its role is unknown but is compatible with transport of a signalling molecule. Homology between the two branches of the superfamily is seen most easily at the ends of the protein. The central regions are poorly conserved within each branch and may not be homologous between branches.
Ribonuclease H2, subunit A (RNase_H2_suA)
Type: Family

Whereas bacterial and archaeal RNases H2 are active as single polypeptides, the Saccharomyces cerevisiae (Baker's yeast) homologue, Rnh2Ap, when expressed in Escherichia coli, fails to produce an active RNase H2. For RNase H2 activity three proteins are required [Rnh2Ap (Rnh201p), Ydr279p (Rnh202p) and Ylr154p (Rnh203p)]. Deletion of any one of the proteins or mutations in the catalytic site in Rnh2A leads to loss of RNase H2 activity . RNase H2 is an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. It participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication.

This entry represents the catalytic chain of RNase H2, which is found as a single polypeptide in prokaryotes and is part of a three protein complex in eukaryotes. In Saccharomyces cerevisiae (Baker's yeast) it is represented by

.
HisA/HisF-like protein, archaeal (HisA/F-archaeal)
Type: Family

This family of proteins has so far been found in three archaeal species: Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum), Methanocaldococcus jannaschii (Methanococcus jannaschii), and Archaeoglobus fulgidus. Proteins are homologous to phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (HisA) and, with lower similarity, to the cyclase HisF, both of which are enzymes of histidine biosynthesis. Each species with this protein also encodes HisA. However, the function of proteins in this group is unknown.
Histidine biosynthesis, HisF (HisF)
Type: Family

Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteins involved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called
His6 and His7 in eukaryotes and HisA and HisF in prokaryotes . HisA is a phosphoribosylformimino-5-aminoimidazole carboxamide ribonucleotide isomerase (

), involved in the fourth step of histidine biosynthesis. The bacterial HisF protein is a cyclase which catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during the sixth step of histidine biosynthesis. HisF is also known as imidazole glycerol phosphate synthase . The yeast His7 protein is a bifunctional protein which catalyzes an amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the ribonucleotide used for purine biosynthesis. The enzyme also catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.

This family describes the histidine biosynthesis protein, HisF.
tRNA-dihydrouridine synthase DusB-like (DusB-like)
Type: Family

This family represents tRNA-dihydrouridine synthases from the nifR3 family that includes NifR3 itself, from Rhodobacter capsulatus and DusB from E. coli . Members of this family catalyse the reduction of the 5,6-double bond of a uridine residue on tRNA. Dihydrouridine modification of tRNA is widely observed in prokaryotes and eukaryotes , and also in some archaea. Most dihydrouridines are found in the D loop of t-RNAs. The role of dihydrouridine in tRNA is currently unknown, but may increase conformational flexibility of the tRNA.
tRNA-dihydrouridine(20/20a) synthase (DusA)
Type: Family

Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. D is formed by reduction of the carbon-carbon double bond at positions 5 and 6 of the uridine base by dihydrouridine synthases (Dus), and is mostly found in the D-loop of tRNAs for which it is named .

This entry represents DusA (also known as tRNA-dihydrouridine(20/20a) synthase), which specifically modifies U20 and U20a in tRNAs .
Glucokinase ROK (ROK_glcA)
Type: Family

This family describes one branch of the ROK superfamily of proteins that may have activity as glucokinase. Glucokinase is required for glucose repression of many different genes .
Beta-ketoacyl-[acyl-carrier-protein] synthase III (FabH)
Type: Family

Beta-ketoacyl-[acyl-carrier-protein] synthase III (FabH) generally initiates elongation in type II fatty acid synthase systems found in bacteria and plants. It is responsible for producing the multitude of fatty acid structures found in bacterial membranes . The two members of this subfamily from Bacillus subtilis differ from each other, and from FabH from Escherichia coli, in acyl group specificity. Active site residues include Cys112, His244 and Asn274 of Escherichia coli FabH. Cys-112 is the site of acyl group attachment.
Hydroxymethylglutaryl-CoA synthase (HMG_CoA_Synthase)
Type: Family

This entry represents Hydroxymethylglutaryl-CoA synthase and related prokaryotic proteins. These proteins show considerable similarity and identical active site residues to FabH, the beta-ketoacyl-acyl carrier protein synthase III of bacteria and plants. They catalyze the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). These enzymes function in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds that are building blocks of archaeal membrane lipids. In Methanocaldococcus jannaschii (Methanococcus jannaschii)

, Cys-112 is the site of acyl group attachment and His-234 and Asn-237 are also active site residues by homology to FabH.
1,4-dihydroxy-2-naphthoate octaprenyltransferase (MenA)
Type: Family

This membrane-associated enzyme converts 1,4-dihydroxy-2-naphthoic acid (DHNA) to demethylmenaquinone (DMK), a step in menaquinone biosynthesis. A key reaction in the biosynthesis of menaquinone involves the conversion of the soluble bicyclic naphthalenoid compound 1, 4-dihydroxy-2-naphthoic acid (DHNA) to the membrane-bound demethylmenaquinone .
Outer membrane lipoprotein Slp (OMP_Slp)
Type: Family

Slp superfamily members are present in the Gram-negative gammaproteobacteria Escherichia coli (which also contains a close paralog), Haemophilus influenzae and Pasteurella multocida and Vibrio cholerae. The known members of the family to date share a motif LX[GA]C near the N terminus, which is compatible with the possibility that the protein is modified into a lipoprotein with Cys as the new N terminus. Slp from E. coli is known to be a lipoprotein of the outer membrane and to be expressed in response to carbon starvation .
Ribonuclease E/G (RNase_E/G)
Type: Family

Ribonuclease E and ribonuclease G are related enzymes that cleave a wide variety of RNAs . In Escherichia coli, both enzymes have been shown to play a role in the maturation of the 5' end of 16S RNA . RNase E is a major subunit the eubacterial degradosome - a large, multiprotein, multienzyme complex involved in RNA processing and degradation in E. coli and other proteobacteria . These enzymes prefer 5'-monophosphorylated 5'-triphosphorylated substrates. The 5'-monophosphate-assisted cleavage requires at least 2 and preferably 3 or more unpaired 5'-terminal nucleotides .
Pyruvate dehydrogenase E1 component (PDH_E1)
Type: Family

Most members of this family are pyruvate dehydrogenase complex, E1 component. It includes a counterexample from Pseudomonas putida, MdeB, that is active as an E1 component of an alpha-ketoglutarate dehydrogenase complex rather than a pyruvate dehydrogenase complex. The second pyruvate dehydrogenase complex E1 protein from Ralstonia eutropha (Alcaligenes eutrophus), PdhE, complements an aceE mutant of Escherichia coli but is not part of a pyruvate dehydrogenase complex operon, is more similar to the Pseudomonas putida MdeB than to E. coli AceE, and may have also have a different primary specificity.
L-ribulose-5-phosphate 4-epimerase (AraD)
Type: Family

L-ribulose-phosphate 4-epimerase (phosphoribulose isomerase) converts L-ribulose 5-phosphate to D-xylulose 5-phosphate. The structure of L-ribulose-5-phosphate 4-epimerase from Escherichia coli has been solved to 2.4 A resolution. The structure is homo-tetrameric and displays C(4) symmetry. Each subunit has a single domain comprised of a central β-sheet flanked on either side by layers of α-helices. The active site is identified by the position of the catalytic zinc residue and is located at the interface between two adjacent subunits. A remarkable feature of the structure is that it shows a very close resemblance to that of L-fuculose-1-phosphate aldolase,

. This is consistent with the notion that both enzymes belong to a superfamily of epimerases/aldolases that catalyse carbon-carbon bond cleavage reactions via a metal-stabilised enolate intermediate. Detailed inspection of the epimerase structure, however, indicates that despite the close overall structural similarity to class II aldolases, the enzyme has evolved distinct active site features that promote its particular chemistry .
Acetylglutamate kinase family (AcgluKinase_fam)
Type: Family

N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymatic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined .

The pathway from glutamate to arginine is:

NAGS; N-acetylglutamate synthase (

) (glutamate to N-acetylglutamate)

NAGK; N-acetylglutamate kinase (

) (N-acetylglutamate to N-acetylglutamate-5P)

N-acetyl-gamma-glutamyl-phosphate reductase (

) (N-acetylglutamate-5P to N-acetylglumate semialdehyde)

Acetylornithine aminotransferase (

) (N-acetylglumate semialdehyde to N-acetylornithine)

Acetylornithine deacetylase (

) (N-acetylornithine to ornithine)

Arginase (

) (ornithine to arginine)

This family includes acetylglutamate kinase and related enzymes [LysW]-aminoadipate/[LysW]-glutamate kinase (LysZ), which is involved both in the biosynthesis of lysine and arginine , and [LysW]-aminoadipate kinase .
Lon protease, archaeal (Lon_arc)
Type: Family

This entry defines the archaeal lon protease homologues, which are ATP-dependent serine peptidases belonging to peptidase family S16 (lon protease family). A lon protease from Thermococcus kodakaraensis has been characterised and displays ATP-independent proteolytic activity towards unfolded proteins and ATP-dependent activity for folded proteins, suggesting a different mode of action from its bacterial counterpart .
Transcription termination factor Rho (Term_rho)
Type: Family

Rho-dependent transcription terminators participate in sophisticated genetic regulatory mechanisms, in both bacteria and phages; they occur in regulatory regions preceding the coding sequences of genes and within coding sequences, as well as at the end of transcriptional units, to prevent read through transcription. Rho is the main factor required for termination; it is a ring-shaped hexameric protein with ATPase and helicase activities. Rho-dependent termination occurs by binding of Rho to ribosome-free mRNA, C-rich sites being good candidates for binding. Rho's ATPase is activated by Rho-mRNA binding, and provides the energy for Rho translocation along the mRNA; translocation requires sliding of the message into the central hole of the hexamer. When a polymerase pause site is encountered, the actual termination occurs, and the transcript is released by Rho's helicase activity .
Ribosomal bS6 modification enzyme RimK/Lysine biosynthesis enzyme LysX (Rp_bS6_RimK/Lys_biosynth_LsyX)
Type: Family

The family of proteins found in this family include the characterised LysX from
Thermus thermophilus
which is part of a well-organised lysine biosynthesis gene cluster . LysX is believed to carry out an ATP-dependent acylation of the amino group of alpha-aminoadipate in the prokaryotic version of the fungal AAA lysine biosynthesis pathway. No species having a sequence in this family contains the elements of the more common diaminopimelate lysine biosythesis pathway, and none has been shown to be a lysine auxotroph. These sequences have mainly recieved the name of the related enzyme, "ribosomal protein bS6 modification protein RimK". RimK has been characterised in
Escherichia coli
, and acts by ATP-dependent condensation of bS6 with glutamate residues .
ADP/ATP carrier protein, bacterial type (ADP_ATP_car_bac_type)
Type: Family

These proteins are members of the ATP:ADP Antiporter (AAA) family, which consists of nucleotide transporters that have 12 GES predicted transmembrane regions. One protein from Rickettsia prowazekii functions to take up ATP from the eukaryotic cell cytoplasm into the bacterium in exchange for ADP. Five AAA family paralogues are encoded within the genome of R. prowazekii. This organism transports UMP and GMP but not CMP, and it seems likely that one or more of the AAA family paralogues are responsible. The genome of Chlamydia trachomatis encodes two AAA family members, Npt1 and Npt2, which catalyse ATP/ADP exchange and GTP, CTP, ATP and UTP uptake probably employing a proton symport mechanism. Two homologous adenylate translocators of Arabidopsis thaliana are postulated to be localized to the intracellular plastid membrane where they function as ATP importers.

This family contains bacterial proteins as well as chloroplastic proteins found in plants.
Anaerobic c4-dicarboxylate membrane transporter (Anaer_Dcu_memb_transpt)
Type: Family

These proteins are members of the C4-Dicarboxylate Uptake (Dcu) family. Most proteins in this family are predicted to have 12 GES predicted transmembrane regions; however the one member whose membrane topology has been experimentally determined has 10 transmembrane regions, with both the N- and C-termini localized to the periplasm . The DcuA and DcuB proteins are involved in the transport of aspartate, malate, fumarate and succinate in many species , and are thought to function as antiporters with any two of these substrates. Since DcuA is encoded in an operon with the gene for aspartase, and DcuB is encoded in an operon with the gene for fumarase, their physiological functions may be to catalyze aspartate:fumarate and fumarate:malate exchange during the anaerobic utilization of aspartate and fumarate, respectively . The Escherichia coli DcuA and DcuB proteins have very different expression patterns . DcuA is constitutively expressed; DcuB is strongly induced anaerobically by FNR and C4-dicarboxylates, while it is repressed by nitrate and subject to CRP-mediated catabolite repression.
C4-dicarboxylate anaerobic carrier (C4_dicarb_anaerob_car)
Type: Family

Escherichia coli contains four different secondary carriers (DcuA, DcuB, DcuC, and DctA) for C4-dicarboxylates DcuA is used for aerobic growth on C4-dicarboxylates , whereas the Dcu carriers (encoded by the dcuA, dcuB, and dcuC genes) are used under anaerobic conditions and form a distinct family of carriers . Each of the Dcu carriers is able to catalyze the uptake, antiport, and possibly also efflux of C4-dicarboxylates. DcuB is the major C4-dicarboxylate carrier for fumarate respiration with high fumarate-succinate exchange activity. It is synthesized only in the absence of oxygen and nitrate and in the presence of C4-dicarboxylates . DcuA is expressed constitutively in aerobic and anaerobic growth and can substitute for DcuB .

These proteins are members of the C4-dicarboxylate Uptake C (DcuC) family. DcuC has 12 GES predicted transmembrane regions, is induced only under anaerobic conditions, and is not repressed by glucose. DcuC may therefore function as a succinate efflux system during anaerobic glucose fermentation. However, when overexpressed, it can replace either DcuA or DcuB in catalyzing fumarate-succinate exchange and fumarate uptake . DcuC shows the same transport modes as DcuA and DcuB (exchange, uptake, and presumably efflux of C4-dicarboxylates) .
Na+/H+ antiporter NhaA (NhaA)
Type: Family

NhaA is a sodium ion/proton antiporter that uses the proton electrochemical gradient to expel sodium ions from the cytoplasm and functions primarily in the adaptation to high salinity at alkaline pH. NhaA is also believed to be responsible for adaptation to alkaline pH when sodium is available. NhaA is one of the three known sodium ion/proton antiporters in Escherichia coli along with NhaB and ChaA, though there are other mechanisms for Na+ extrusion such as NDH-I complicating the determination of the precise roles of each of the transporters .
Na+/H+ antiporter NhaB (Na+/H+_antiporter_NhaB)
Type: Family

The Escherichia coli NhaB Na+:H+ Antiporter (NhaB) protein has 12 predicted TMS, and catalyses sodium/proton exchange. Unlike NhaA,

, this activity is not pH dependent.
Na(+)/H(+) antiporter NhaD (Na(+)/H(+)_antiporter_NhaD)
Type: Family

These proteins are members of the NhaD Na(+)/H(+) antiporter (NhaD) Family (TC 2.A.62) and include the NhaD protein of Vibrio parahaemolyticus which has been characterised . It has 12 predicted transmembrane regions and has been shown to catalyse Na+/H+ antiport, though Li+ can also be a substrate.
L-rhamnose-proton symport, RhaT (L-rhamnose-proton_sym_RhaT)
Type: Family

These proteins are members of the L-Rhamnose Symporter (RhaT) family. This family includes two characterised members, both of which function as L-rhamnose:H+ symporters and have 10 GES predicted transmembrane domains.
Alkylhydroperoxidase AhpD (AhpD)
Type: Family

Alkyl hydroperoxide reductase AhpD catalyse the reduction of peroxides to their corresponding alcohols via oxidation of cysteine residues. In these alkylhydroperoxidases, the cysteines are located in a conserved -CXXC- motif located towards the C terminus. In Mycobacterium tuberculosis, two non-homologous alkylhydroperoxidases, AhpD and AhpC, are found in the same operon. This entry represents AhpD, which is a component of alkyl-hydroperoxide reductase participating in defense against ROS and ROS produced by host immune cells .
Alkylhydroperoxidase AhpD core (AhpD_core)
Type: Domain

This entry represents a 51-residue core region of homology among a group of mostly uncharacterised proteins of 110 to 227 amino acids. Most members in this entry contain the motif Exxxxxx[SA]xxxxC[VIL]xCxxxH. Proteins containing this domain include the alkylhydroperoxidase AhpD of Mycobacterium tuberculosis, a macrophage infectivity potentiator peptide of Legionella pneumophila, and an uncharacterised peptide in the tetrachloroethene reductive dehalogenase operon of Dehalospirillum multivorans. These proteins may have alkylhydroperoxidase or related antioxidant activity.
Cadmium resistance transporter (Cd-R_transporter)
Type: Family

These proteins are members of the Cadmium Resistance (CadD) family. The CadD family includes two close orthologues in two Staphylococcus species that have been reported to function in cadmium resistance .
Cytochrome c oxidase cbb3-type, subunit I (Cyt_c_oxidase_cbb3_su1)
Type: Family

This family represents the largest subunit, I, of the ccb3-type cytochrome c oxidase

, with two protohaem's and copper. It shows strong homology to subunits of other types of cytochrome oxidases. Species with this type, all from the proteobacteria so far, include Neisseria meningitidis, Helicobacter pylori, Campylobacter jejuni, Rhodobacter sphaeroides, Rhizobium leguminosarum, amongst others.
Cytochrome c oxidase cbb3-type, subunit III (Cyt_c_oxidase_cbb3_su3)
Type: Family

This family describes a di-haem subunit of approximately 26kDa of the cbb3 type copper and haem-containing cytochrome oxidase

.
2-hydroxycarboxylate transporter (2-OHcarboxylate_transport)
Type: Family

The 2-hydroxycarboxylate transporter family is a family of secondary transporters found exclusively in the bacterial kingdom. They function in the metabolism of the di- and tricarboxylates malate and citrate, mostly in fermentative pathways involving decarboxylation of malate or oxaloacetate .

The majority of proteins in this family are known or predicted members of the citrate:cation symporter (CCS) family. They contain the predicted twelve-transmembrane helix motif common to many secondary transporters . Most of the characterised proteins in this entry are specific for citrate, with either Na+ of H+ as the contransported cation. However, one member is capable of cotransporting either citrate or malate with H+ , while another has been shown to be an Na+-dependent malate cotransporter .
Citrate transporter-like domain (Cit_transptr-like_dom)
Type: Domain

This domain is found in proteins belonging to the CitM transporter, NhaD Na+/H+ antiporter and Na+/sulfate symporter families, such as CitM from Bacillus subtilis , NhaD from Halomonas elongata and SLT1 from Chlamydomonas reinhardtii .
TRAP transporter large membrane protein DctM (TRAP_DctM)
Type: Family

The tripartite ATP-independent periplasmic (TRAP) transport system is firmly established as a new type of extracytoplasmic solute receptor (ESR)-dependent uptake systems, unrelated to ABC transporters. In TRAP transport systems the driving force for solute accumulation is an electrochemical ion gradient and not ATP hydrolysis . The first TRAP transporter to be characterised was the high-affinity C4-dicarboxylate transport (Dct) system from Rhodobacter capsulatus . This consists of three proteins; an ESR (DctP) and small (DctQ) and large (DctM) integral membrane proteins.

This entry represents a family of TRAP transporter permease proteins, including DctM, SiaM (involved in sialic acid uptake ) and YiaN (involved in the uptake of 2,3-diketo-L-gulonate ).