SII-SWORD/CoKE huggingface dataset:
Ribulokinase (Ribulokinase)
Type: Family

L-ribulokinase (

) catalyses the MgATP-dependent phosphorylation of L(or D)-ribulose to produce L(or D)-ribulose 5-phosphate and ADP, which is the second step in arabinose catabolism:

ATP + L/D-ribulose = ADP + L/D-ribulose 5-phosphate

These proteins can also phosphorylates a variety of other sugar substrates including ribitol and arabitol.
Pyruvate carboxylase (Pyruv_COase)
Type: Family

In the postabsorptive state, blood glucose concentration is kept constant by a combination of glycogenolysis and gluconeogenesis. During prolonged fasting, when hepatic glycogen is exhausted, gluconeogenesis becomes the only source of plasma glucose. Gluconeogenesis (the production of new glucose molecules) occurs mainly in liver and, to a small extent, in kidneys.

Pyruvate carboxylase (

), a member of the biotin-dependent enzyme family, catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate, thus playing a crucial role in gluconeogenesis.
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
Most well characterised forms of active enzyme consist of four identical subunits arranged in a tetrahedron-like structure. Each subunit contains three functional domains: the biotin carboxylation domain, the transcarboxylation domain and the biotin carboxyl carrier domain.
Delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH/ALDH4A1)
Type: Family

This entry represents one of two related branches of delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH,

; also known as ALDH4A1 in humans). It is responsible for the NAD
+
-dependent, irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate . This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. P5CDH is a mitochondrial homodimer and a member of the aldehyde dehydrogenase (ALDH) protein superfamily.
1-pyrroline-5-carboxylate dehydrogenase (RocA)
Type: Family

This entry represents a group of 1-pyrroline-5-carboxylate dehydrogenases (RocA) from Bacillales and other bacteria . They are related to delta-1-pyrroline-5-carboxylate dehydrogenase (

;

) , which is an aldehyde dehydrogenase that catalyses the oxidation of glutamate semialdehyde to glutamate , utilizing NAD+ as the electron acceptor. In some bacteria, the two enzymes are fused into the bifunctional flavoenzyme, proline utilization A (PutA) . In this entry, monofunctional enzyme sequences such as seen in the Bacillus subtilis RocA P5CDH are also present . These enzymes play important roles in cellular redox control, superoxide generation, and apoptosis.
Bifunctional protein PutA, C-terminal domain (PutA_C)
Type: Domain

This entry represents the C-terminal domain of Bifunctional protein PutA from Escherichia coli and similar sequences predominantly found in proteobacteria. This domain corresponds to the aldehyde dehydrogenase activity (Delta-1-pyrroline-5-carboxylate dehydrogenase,

) of PutA, which is critical in the de novo biosynthesis of proline and ornithine. It is the rate-limiting enzyme in proline biosynthesis and is subject to feedback inhibition by proline. Structurally, this domain shows two lobes, one that binds NAD+ using a nonclassical Rossmann fold and another harbours the catalytic cysteine .
Diphosphomevalonate/phosphomevalonate decarboxylase (Mev_decarb)
Type: Family

This group of enzymes belongs to the GHMP kinase domain superfamily. GHMP kinases are a unique class of ATP-dependent enzymes (the abbreviation of which refers to the original members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) . Enzymes belonging to this superfamily contain three well-conserved motifs, the second of which has the typical sequence Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala and is involved in ATP binding . The phosphate binding loop in GHMP kinases is distinct from the classical P-loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P-loop-containing proteins . GHMP kinases display a distinctly bilobal appearance with their N-terminal subdomains dominated by a mixed β-sheet flanked on one side by α-helices and their C-terminal subdomains containing a four stranded anti-parallel β-sheet .

The classical mevalonate (MVA) pathway involves decarboxylation of mevalonate diphosphate, while an alternate pathway involves decarboxylation of mevalonate monophosphate. The enzyme responsible is known as phosphomevalonate decarboxylase .
ATP-dependent zinc metalloprotease, FtsH (FtsH)
Type: Family

This entry represents the ATP-dependent zinc metalloprotease FtsH family.

AAA proteases are ATP-dependent metallopeptidases present in eubacteria as well as in organelles of bacterial origin, i.e., mitochondria and chloroplasts. The AAA proteases are also known as FtsH, referring to the Escherichia coli enzyme (Filamentous temperature sensitive H). Most bacteria have a single gene encoding FtsH, three genes are present in yeast and humans, while 12 orthologs have been found in the genome of plants .

E. coil FtsH is a membrane-anchored ATP-dependent protease that degrades misfolded or misassembled membrane proteins as well as a subset of cytoplasmic regulatory proteins. FtsH is a 647-residue protein of 70kDa, with two putative transmembrane segments towards its N terminus which anchor the protein to the membrane, giving rise to a periplasmic domain of 70 residues and a cytoplasmic segment of 520 residues containing the ATPase and protease domains .

The main function of organellar AAA/FtsH proteases is selective degradation of non-assembled, incompletely assembled and/or damaged membrane-anchored proteins. Additional functions of the AAA/FtsH proteases that are not directly connected with protein quality control are processing of pre-proteins, dislocation of membrane proteins or degradation of regulatory proteins .
AAA ATPase, CDC48 family (AAA_ATPase_CDC48)
Type: Family

This family includes yeast CDC48 (cell division control protein 48) and the human orthologue, transitional endoplasmic reticulum ATPase (valosin-containing protein) . It also includes CDC48 homologues from Archaea . These proteins in eukaryotes are involved in the budding and transfer of membrane from the transitional endoplasmic reticulum to the Golgi apparatus. The archeal homologue of eukaryotic CDC48/p97 functions with the 20S proteasome by unfolding substrates and passing them on for degradation . CDC48 consists of an N-terminal domain that binds two hexameric ATPase rings (D1 and D2) surrounding a central pore .
Beta-lactamase hydrolase-like protein, phosphatase-like domain (BLH_phosphatase-like)
Type: Domain

This domain is found N-terminal to a beta-lactamase domain, and it may have phosphatase activity . This domain is found in Beta-lactamase hydrolase-like protein from Agrobacterium fabrum, which may play a role in cell adherence or biofilm development .
Anthranilate phosphoribosyl transferase (Anthranilate_Pribosyl_Tfrase)
Type: Family

In many widely different species, including Escherichia coli, Thermotoga maritima, and Archaeoglobus fulgidus, this enzyme is a C-terminal part of a multifunctional protein together with glutamine amidotransferase; the fusion protein is designated anthranilate synthase component II (

).
Succinyl-diaminopimelate desuccinylase, proteobacteria (DapE_proteobac)
Type: Family

This entry represents succinyl-diaminopimelate desuccinylase from proteobacteria (DapE,

), which hydrolyses N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid (L,L-DAP) . L,L-DAP is required for the bacterial synthesis of lysine and meso-diaminopimelic acid.

It has been shown that DapE is essential for cell growth and proliferation. DapEs have been purified from Escherichia coli and Haemophilus influenzae, while the genes that encode for DapEs have been sequenced from several bacterial sources such as Corynebacterium glutamicum, Helicobacter pylori, Neisseria meningitidis and Mycobacterium tuberculosis. DapE is a small, dimeric enzyme that requires two zinc atoms per molecule for full enzymatic activity. All of the amino acids that function as metal binding ligands are strictly conserved in DapE .
Daunorubicin resistance protein C (Daunbcin-R_C)
Type: Family

Daunorubicin resistance protein C confers the function of daunorubicin resistance. The protein seems to share strong sequence similarity to UvrA proteins, which are involved in excision repair of DNA. Disruption of drrC gene showed increased sensitivity upon exposure to duanorubicin, however it failed to complement uvrA mutants to exposure to UV irradiation. The mechanism on how it confers duanomycin resistance is unclear, but has been suggested to be different from DrrA and DrrB which are antiporters.
Proline iminopeptidase (Pro_iminopeptidase)
Type: Family

This entry describes a family of proline iminopeptidases (

), which are Mn2+-requiring enzymes present in the cytosol of mammalian and microbial cells. They release an N-terminal residue from a peptide, preferably (but not exclusively) a proline.
Proline-specific peptidase (Pro_imino_pep)
Type: Family

This entry describes a subfamily of the α/β fold family of hydrolases. Characterised members include prolyl aminopeptidases, also known as Proline iminopeptidase (PAP,

), and L-amino acid amidase (

).
Ribose-phosphate pyrophosphokinase (Rib-P_diPkinase)
Type: Family

Ribose-phosphate diphosphokinase, also known as ribose-phosphate pyrophosphokinase (RPPK), or phosphoribosyldiphosphate synthetase (

), catalyses the transfer of an intact diphosphate (PP) group from ATP to ribose-5-phosphate (R-5-P), which results in the formation of AMP and 5-phospho-D-ribosyl--1-diphosphate (PRPP).
Thiamine/thiamin pyrophosphate-binding periplasmic protein, ABC transporter (ThiB-like)
Type: Family

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

This entry includes thiB from Proteobacteria and its homologues from Archaea, Actinobacteria, Euryarchaeota and other bacteria. ThiB is a thiamine/thiamine pyrophosphate-binding protein and part of the ABC transporter complex ThiBPQ involved in thiamine import. ThiBPQ is required for transport of thiamine and thiamine pyrophosphate in Salmonella typhimurium . This entry also includes tbpA from E. coli .
Formate acetyltransferase (Form_AcTrfase)
Type: Family

Pyruvate formate-lyase

(also known as formate C-acetyltransferase) is an enzyme which converts acetyl-CoA and formate to CoA and pyruvate.

Acetyl-CoA + formate = CoA + pyruvate
In Escherichia coli, it uses a radical mechanism to reversibly cleave the C1-C2 bond of pyruvate using the Gly 734 radical and two cysteine residues (Cys 418, Cys 419) .

This family comprises formate acetyltransferase 1. More distantly related putative formate acetyltransferases have also been identified, including formate acetyltransferase 2 from E. coli, which is excluded from this model.
Molybdate ABC transporter, substrate-binding protein (ModA)
Type: Family

This entry represents the molybdate ABC transporter periplasmic binding protein from bacteria and archaea. It has been shown experimentally by radioactive labeling that ModA is a hydrophylioc periplasmic-binding protein in Gram-negative organisms and its counterpart in Gram-positive organisms is a lipoprotein. The other components of the system include ModB, an integral membrane protein and ModC, the ATP-binding subunit. Almost all of them display a common β/α folding motif and have similar tertiary structures consisting of two globular domains.

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .
Retinal-specific ATP-binding cassette transporter (ABCA4/ABCR)
Type: Family

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .

Retinal-specific ATP-binding cassette transporter ABCA4 (also known as the Rim protein, ABCR) is a eukaryotic protein belonging to the ABC-A subfamily of the ABC transporter family. In humans, ABCA4 is localised with opsin photopigments in outer segment disc membranes of rod and cone photoreceptor cells. It serves as an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer . Mutations in the ABCA4 gene cause Stargardt macular degeneration, a recessive disease characterised by the loss in central vision, progressive bilateral atrophy of photoreceptor and retinal pigment epithelial (RPE) cells, accumulation of fluorescent deposits in the macula, and a delay in dark adaptation .
Phosphoglycerate mutase 1 (Phosphogly_mut1)
Type: Family

Most members of this family are phosphoglycerate mutases (

) . This enzyme interconverts 2-phosphoglycerate and 3-phosphoglycerate.
2-phospho-D-glycerate + 2,3-diphosphoglycerate = 3-phospho-D-glycerate + 2,3-diphosphoglycerate.
The enzyme is transiently phosphorylated on an active site histidine by 2,3-diphosphoglyerate, which is both substrate and product. Some members of this family have phosphoglycerate mutase as a minor activity and act primarily as a bisphoglycerate mutase, interconverting 2,3-diphosphoglycerate and 1,3-diphosphoglycerate (

) .
ATP synthase, F0 complex, subunit C, bacterial/chloroplast (ATP_synth_csu_bac/chlpt)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

This entry represents subunit C (also called subunit 9, or proteolipid) found in the F0 complex of F-ATPases from bacterial plasma membranes and chloroplast thylakoid membranes. The flux of protons through the ATPase channel drives the rotation of the C subunit ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the C subunit ring of F0. The sequential protonation and deprotonation of Asp61 of subunit C is coupled to the stepwise movement of the rotor .
Histidine biosynthesis bifunctional protein, N-terminal histidinol-phosphatase domain (HisB_N)
Type: Domain

This entry describes a histidinol phosphatase domain. This domain occurs in Histidine biosynthesis bifunctional protein HisB at the N-terminal region, followed by an imidazoleglycerol-phosphate dehydratase domain (

). These enzymatic domains catalyse the ninth and seventh steps, respectively, of histidine biosynthesis .
Glutathione S-transferases, class Zeta (GST_Zeta)
Type: Family

GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal α helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain .
4-hydroxyphenylpyruvate dioxygenase (4OHPhenylPyrv_dOase)
Type: Family

4-hydroxyphenylpyruvate dioxygenase (

) oxidises 4-hydroxyphenylpyruvate, a tyrosine and phenylalanine catabolite, to homogentisate. Homogentisate can undergo a further non-enzymatic oxidation and polymerisation into brown pigments that protect some bacterial species from light. A similar process occurs spontaneously in blood and is haemolytic . In some bacterial species, this enzyme has been studied as a haemolysin.
Tyrosine aminotransferase (Tyrosine_aminoTrfase)
Type: Family

This entry describes tyrosine aminotransferase (

) as found in animals and Trypanosoma cruzi (Euglenozoa). It is the first enzyme of a pathway of tyrosine degradation via homogentisate.

L-tyrosine + 2-oxoglutarate = 4-hydroxyphenylpyruvate + L-glutamate.
Tyrosine/nicotianamine aminotransferase (TyrNic_aminoTrfase)
Type: Family

This subfamily of pyridoxal phosphate-dependent enzymes includes known examples of both tyrosine aminotransferase from animals and nicotianamine aminotransferase from barley.
Fumarylacetoacetase (Fumarylacetoacetase)
Type: Family

Fumarylacetoacetase (

; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation . This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinemia, which is associated with liver and kidney abnormalities and neurological disorders . The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole . FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures .

In Aspergillus fumigatus, this enzyme is part of the L-tyrosine degradation gene cluster that mediates the biosynthesis of the brownish pigment pyomelanin as an alternative melanin .
Phenylalanine-4-hydroxylase, monomeric form (Phe-4-hydroxylase_mono)
Type: Family

This entry represents the small, monomeric form of phenylalanine-4-hydroxylase (PAH;

), as found in a certain Gram-negative bacteria. The enzyme is biopterin and metal dependent, and acts to irreversibly convert phenylalanine to tyrosine, the rate-limiting step in phenylalanine catabolism in some systems:

L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + dihydrobiopterin + H2O

The structure of PAH from Colwellia psychrerythraea (strain 34H / ATCC BAA-681), which binds tetrahydrobiopterin (BH4) as cofactor, is a cold-active form of the enzyme that has increased stability and flexibility around the active site .
Phenylalanine-4-hydroxylase, tetrameric form (Phe-4-hydroxylase_tetra)
Type: Family

This entry represents the large, tetrameric form of phenylalanine-4-hydroxylase (PAH;

), as found in metazoans. PAH irreversibly converts phenylalanine to tyrosine, and is known to be the rate-limiting step in phenylalanine catabolism in some systems. It is closely related to metazoan tyrosine 3-monooxygenase and tryptophan 5-monoxygenase, and more distantly to monomeric phenylalanine-4-hydroxylases of some Gram-negative bacteria. The member of this family from Drosophila has been described as having both phenylalanine-4-hydroxylase and tryptophan 5-monoxygenase activity . However, a Drosophila member of the tryptophan 5-monoxygenase clade has subsequently been discovered.

A deficiency in PAH can lead to phenylketonuria (PKU), an autosomal recessive genetic disorder characterised by an inability to metabolise phenylalanine, resulting in elevated Phe levels in the bloodstream that can lead to mental retardation if left untreated .
Tyrosine 3-monooxygenase (Tyr_3_mOase)
Type: Family

Tyrosine 3-monooxygenase (

), is a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tryptophan 5-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. It catalyses the first step in catecholamine biosynthesis.

L-tyrosine + tetrahydropteridine + O2 = 3,4-dihydroxy-L-phenylalanine + dihydropteridine + H2O.
Tryptophan 5-monooxygenase (Trp_5_mOase)
Type: Family

Tryptophan 5-monooxygenase (

) is a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tyrosine 3-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. It is the rate-limiting enzyme in the biosynthesis of serotonin in the central nervous system and catalyzes the first step of the synthesis of melatonin in the pineal gland .
L-tryptophan + tetrahydropteridine + O2 = 5-hydroxy-L-tryptophan + dihydropteridine + H2O
Bacterial glucose/galactose transporter (Glc/Gal_transptr_bac)
Type: Family

This model describes the glucose/galactose transporter in bacteria. Putative transporters in bacterial species have been isolated by functional complementation, which restored its functional activity. These two transporters are members of the major facilitator superfamily, FHS, in which they represent a previously undescribed family .
1-aminocyclopropane-1-carboxylate deaminase (ACP_carboxylate_deaminase)
Type: Family

1-aminocyclopropane-1-carboxylate deaminase (

) is a pyridoxal phosphate-dependent enzyme which catalyses a cyclopropane ring-opening reaction, the irreversible conversion of 1-aminocyclopropane-1-carboxylate (ACC) to ammonia and alpha-ketobutyrate . In plants, the latter is a precursor of the ripening hormone ethylene . Some plant growth-promoting rhizobacteria can produce 1-aminocyclopropane-1-carboxylate deaminase to enhance plant growth .