SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase subunit Rpo4 (Rpo4)
Type: Family

Eukaryotic RNA polymerase II (RNAPII) is composed of a ten-subunit core and an Rpb4-Rpb7 heterodimer that reversibly associates with the core . The heterodimer both binds RNA and serves to stabilise the transcription complex. The Rpb4 and Rpb7 homologues in Archaea are known as subunits F and E, and have been more recently renamed as Rpo4 and Rpo7, respectively . While the Rpb7 homologue is reasonably well conserved, the similarity between the eukaryotic Rpb4 and the archaeal F subunit is barely detectable at the primary sequence level . Like their eukaryotic counterparts, the archaeal E and F subunits have been shown to form a stable heterodimer . Structural studies of the Methanocaldococcus jannaschii (Methanococcus jannaschii) E-F heterodimer indicate that subunit E likely mediates binding to the nascent RNA transcript, while the F subunit serves to stabilise the conformation of the E subunit .

This family represents the archaeal subunit Rpo4 (subunit F).

DNA-directed RNA polymerases, also known as DNA-dependent RNA polymerases, are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. Eukaryotes have three different DNA-directed RNA polymerases (RNAPs), Pol I, II, and III, whereas Archaea and Bacteria have single enzymes.

RNAPs are multisubunit enzymes. Archaeal RNAP is closely related to eukaryotic RNAP II , which consists of 12 subunits. Archaeal RNAP has an additional subunit, Rpo13, with no orthologue in the eukaryotic enzyme .
Class I myosin tail homology domain (Myosin_TH1)
Type: Domain

Class I myosins (Myo1s) are widely expressed in eukaryotic cells. Myo1s exist as monomers and can sense cellular mechanical forces and function as tension- sensitive anchors or transporters. Each Myo1 contains from N terminus to C terminus, a motor domain, a neck region consisting of several calmodulin (CaM)-binding IQ motifs and a tail region. All Myo1s contain a tail homology (TH1) domain featuring an embedded pleckstrin-homology (PH) domain capable of binding to lipid membranes. In addition, Myo1s with long tails also contain a TH2 (or GPA) domain and a C-terminal TH3 (or SH3) domain, the latter of which may be responsible for binding to cargos. All Myo1s are capable of bridging actin cytoskeletons with lipid membranes by using their motor heads and tail TH1 domains.

The TH1 domain is an extended PH domain capable of binding to lipids .
Type IV conjugative transfer system protein TraH (T4SS_TraH)
Type: Family

Six Tra proteins encoded by the F plasmid and required by F(+) cells to elaborate F pili. The six proteins are TraH, TraF, TraW, TraU, TrbI, and TrbB. Except for TrbI, these proteins were all identified as hallmarks of F-like type IV secretion systems (TFSSs), with no homologues among TFSS genes of P-type or I-type systems. With the exception of TrbI, which is an inner membrane protein, the remaining proteins are or are predicted to be periplasmic. TrbI consists of one membrane-spanning segment near its N terminus and an 88-residue, hydrophilic domain that extends into the periplasm . It has been proposed that the TraH interaction group is to control F-pilus extension and retraction during conjugation .
Tyrosinase co-factor MelC1 (MelC1)
Type: Family

This family consists of several tyrosinase co-factor MELC1 proteins from a number of Streptomyces species. The melanin operon (melC) of Streptomyces antibioticus contains two genes, melC1 and melC2 (apotyrosinase). It is thought that MelC1 forms a transient binary complex with the downstream apotyrosinase MelC2 to facilitate the incorporation of copper ion and the secretion of tyrosinase indicating that MelC1 is a chaperone for the apotyrosinase MelC2 .
Flagellar basal-body/hook protein, C-terminal domain (Flg_bb/hook_C_dom)
Type: Domain

This functionally uncharacterised domain is found in the C terminus of flagellar basal-body rod and flagellar hook proteins in which

is often present at the extreme N terminus.
Lactococcus lactis RepB, C-terminal (L_lactis_RepB_C)
Type: Domain

This entry represents the C-terminal region of RepB proteins from Lactococcus lactis.
Large T antigen, polyomavirus, C-terminal (Lg_T_Ag_Polyomavir_C)
Type: Domain

The group of polyomaviruses is formed by the homonymous murine virus (Py) as well as other representative members such as the simian virus 40 (SV40) and the human BK and JC viruses . Their large T antigen (T-ag) protein binds to and activates DNA replication from the origin of DNA replication (ori). Insofar as is known, the T-ag binds to the origin first as a monomer to its pentanucleotide recognition element. The monomers are then thought to assemble into hexamers and double hexamers, which constitute the form that is active in initiation of DNA replication. When bound to the ori, T-ag double hexamers encircle DNA . T-ag is a multidomain protein that contains an N-terminal J domain, which mediates protein interactions (see

,

), a central origin-binding domain (OBD), and a C-terminal superfamily 3 helicase domain (see

,

) .

This entry represents the helicase domain of LTag, which assembles into a hexameric structure containing a positively charged central channel that can bind both single- and double-stranded DNA . ATP binding and hydrolysis trigger large conformational changes which are thought to be coupled to the melting of origin DNA and the unwinding of duplex DNA . These conformational changes cause the angles and orientations between regions of a monomer to alter, creating what was described as an "iris"-like motion in the hexamer. In addition to this, six β hairpins on the channel surface move longitudinally along the central channel, possibly serving as a motor for pulling DNA into the LTag double hexamer for unwinding.
NADH dehydrogenase subunit 2, C-terminal (NADH_DH_su2_C)
Type: Domain

This entry represents the C-terminal region specific to the animal NADH dehydrogenase subunit 2 protein, also known as NADH-ubiquinone oxidoreductase chain 2. This protein is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyses electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor . This domain is found in conjunction with

.
NADH dehydrogenase subunit 5, C-terminal (NADH_DH_su5_C)
Type: Domain

This entry represents the C-terminal region of a group of NADH dehydrogenase subunit 5 proteins from eukaryota and bacteria. Subunit 5 is a core of the mitochondrial membrane respiratory chain NADH dehydrogenase which catalyses electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor . This domain is found in conjunction with

and
SMCs flexible hinge (SMC_hinge)
Type: Domain

This entry represents the hinge region of the SMC (Structural Maintenance of Chromosomes) family of proteins. The hinge region is responsible for formation of the DNA interacting dimer. It is also possible that its precise structure is an essential determinant of the specificity of the DNA-protein interaction .

This region is also found in urease accessory protein 2 (URE2) which is a central component of cohesin, a complex required for chromosome cohesion during the cell cycle, and Is unrelated to urease function in C.neoformans .
Protein of unknown function DUF1131 (DUF1131)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Magnesium-protoporphyrin IX methyltransferase, C-terminal (Mg_prot_MeTrfase_C)
Type: Domain

This entry represents the C terminus (approximately 100 residues) of bacterial and eukaryotic magnesium-protoporphyrin IX methyltransferase (

). This converts magnesium-protoporphyrin IX to magnesium-protoporphyrin IX metylester using S-adenosyl-L-methionine as a cofactor .
Poly-beta-hydroxybutyrate polymerase, N-terminal domain (PhaC_N)
Type: Domain

This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond .
Xanthosine phosphorylase (Xanthosine_phosphorylase)
Type: Family

This entry represents purine nucleotide phosphorylases in the gammaproteobacteria. The gene is part of an operon for the degradation of xanthosine and is induced by xanthosine . The enzyme is also capable of acting on inosine and guanosine, but not adenosine.
AMP nucleosidase, putative (AMN-like)
Type: Family

AMP nucleosidase (AMN) catalyses the hydrolysis of AMP to form adenine and ribose 5-phosphate. It is only found in prokaryotes, where it plays a role in purine nucleoside salvage and intracellular AMP level regulation . The gene for AMP nucleosidase from Escherichia coli (amn) encodes a protein of 483 amino acids. A comparison of the amino acid sequence for AMP nucleosidase with that for yeast AMP deaminase shows that there is a region where only six out of eight amino acids are identical but there is no other overall homology. AMN also showed little similarity to consensus sequences for adenylate binding sites even though the enzyme is known to have a catalytic site for AMP and regulatory sites for MgATP and phosphate .

Members of this protein family, which are found in bacteria, are predicted to be AMP nucleosidases.
Malate dehydrogenase, type 2 (Malate_DH_type2)
Type: Family

Malate dehydrogenases catalyse the interconversion of malate and oxaloacetate using dinucleotide cofactors . The enzymes in this entry are found in archaea, bacteria and eukaryotes and fall into two distinct groups. The first group are cytoplasmic, NAD-dependent enzymes which participate in the citric acid cycle (

). The second group are found in plant chloroplasts, use NADP as cofactor, and participate in the C4 cycle (

).

Structural studies indicate that these enzymes are homodimers with very similar overall topology, though the chloroplast enzymes also have N- and C-terminal extensions, and all contain the classical Rossman fold for NAD(P)H binding . Substrate specificity is determined by a mobile loop at the active site which uses charge balancing to discriminate between the correct substrates (malate and oxaloacetate) and other potential oxo/hydroxyacid substrates the enzyme may encounter within the cell .
Geranylgeranylglyceryl phosphate synthase (GGGP_synth)
Type: Family

This entry represents geranylgeranylglyceryl phosphate synthase which catalyses the first committed step in the synthesis of ether-linked membrane lipids in archaea .
TonB-dependent lactoferrin/transferrin receptor (TonB_lacto/transferrin_rcpt)
Type: Family

This family of TonB-dependent receptors are responsible for import of iron from the mammalian iron carriers lactoferrin and transferrin across the outer membrane. These receptors are found only in bacteria which can infect mammals, examples are Moraxella, Mannheimia, Neisseria, Actinobacillus, Pasteurella, Haemophilus and Histophilus species.

These receptor are part of a two-component system to acquire iron from host transferrin and lactoferrin. The membrane-bound receptor (called TbpA/Tbp1 for transferrin and LbpA for lactoferrin) extracts and transports iron across the outer membrane; a lipoprotein (called TbpB for transferrin and LbpB for lactoferrin) delivers the iron-loaded lactoferrin/transferrin to the transporter .
TonB-dependent haemoglobin/transferrin/lactoferrin receptor (TonB_Hb/transfer/lactofer_rcpt)
Type: Family

This entry represents a family of TonB-dependent outer membrane receptor/transporters acting on iron-containing proteins such as haemoglobin, transferrin and lactoferrin. It contains the haem/haemoglobin receptor family and the transferrin/lactoferrin receptor family. Nearly all of the species, which contain sequences in this family have access to haemoglobin, transferrin or lactoferrin or related proteins in their biological niche and the proteins are therefore most likely to be haemoglobin transporters.

Proteins in this entry includes TbpA from Neisseria meningitidis serogroup B. It can form the transferrin complex that acquires iron by extracting it from serum transferrin (TF) in its human host. It contains the classic fold with a 22-strand transmembrane β-barrel encompassing a plug domain .
Chorismate mutase, archaeal (Chorismate_mutase_arc)
Type: Domain

This entry represents archaeal chorismate mutases. Chorismate mutase catalyses the conversion of chorismate into prephenate which is subsequently converted into either phenylalanine or tyrosine. In Sulfolobus solfataricus this gene is found as a fusion with prephenate dehydrogenase (

) which is the next enzyme in the tyrosine biosynthesis pathway. The Archaeoglobus fulgidus gene contains an N-terminal prephenate dehydrogenase domain and a C-terminal prephenate dehydratase domain (

) followed by a regulatory amino acid-binding ACT domain (

) .
Chorismate mutase, bacteria (CM_bact)
Type: Family

This entry describes monofunctional (non-fused) chorismate mutases (CM) in the actinobacteridae and alphaproteobacteria.
Chorismate mutase, gammaproteobacteria (CM_P_1)
Type: Domain

This entry represents the chorismate mutase domain of gammaproteobacterial 'P-protein' which are bifunctional, containing an N-terminal chorismate mutase domain and a C-terminal prephenate dehydratase domain.
Citrate synthase, type I (Citrate_synthase_typ-I)
Type: Family

This entry describes one of several distinct but closely homologous classes of citrate synthase, the protein that brings carbon (from acetyl-CoA) into the TCA cycle. This form, class I, is known to be hexameric and allosterically inhibited by NADH in Escherichia coli, Acinetobacter anitratum, Azotobacter vinelandii, Pseudomonas aeruginosa, etc. In most species with a class I citrate synthase, a dimeric class II isozyme is found. The class II enzyme may act primarily on propionyl-CoA to make 2-methylcitrate or be bifunctional, may be found among propionate utilization enzymes, and may be constitutive or induced by propionate. Some members of this family group as class I enzymes, and may be hexameric, but have shown regulatory properties more like class II enzymes.
Chorismate mutase, Firmicutes/Deinococcus (Chorismate_mutase_GmP-bac)
Type: Domain

This entry represents the chorismate mutase (CM) domains N-terminally fused to the first enzyme in the chorismate pathway, 2-dehydro-3-deoxyphosphoheptanoate aldolase (DAHP synthetase, AroA) which are found in some Gram-positive species and Deinococcus. Only in Deinococcus, where this domain is the sole CM domain in the genome can a trusted assignment of function be made. In the other species there is at least one other CM domain present. The similarity between the Deinococcus gene and the others in this clade is sufficiently strong (~44% identity), that the whole clade can be trusted to be functional. The possibility exists, however, that in the Gram-positive species the fusion to the first enzyme in the pathway has evolved a separate, regulatory role.
Gamma/beta/epsilon proteobacterial P-protein, chorismate mutase domain (G/b/e-P-prot_chorismate_mutase)
Type: Domain

This entry primarily represents the chorismate mutase domain of the gamma, beta and epsilon proteobacterial 'P-protein', which contains an N-terminal chorismate mutase domain and a C-terminal prephenate dehydratase domain.
Chorismate mutase, high GC Gram-positive bacteria/archaeal (Chorismate_mutase_highGC-bac)
Type: Domain

This entry represents prokaryotic, primarily monofunctional, chorismate mutases of the AroQ class from high GC Gram-positive bacteria and archaea. In Corynebacterium and Pyrococcus, these are the apparently the sole chorismate mutase enzymes in their respective genomes. This is coupled with the presence in those genomes of the enzymes of the chorismate pathways both up- and downstream of chorismate mutase.

The bifunctional members associated with this entry either have an N-terminal 3-dehydroquinate dehydratase domain or a C-terminal prephenate dehydratase domain associated with an amino acid-binding ACT domain.
Flavocytochrome c (Flavocytochrome_c)
Type: Family

This entry describes a family of redox proteins related to the succinate dehydrogenases and fumarate reductases (FRDs) of Escherichia coli, mitochondria, and other well-characterised systems. A member of this family from Shewanella frigidimarina (strain NCIMB 400) is characterised as a water-soluble periplasmic protein with four haem groups, a non-covalently bound FAD, and essentially unidirectional fumarate reductase activity. At least seven distinct members of this family are found in Shewanella oneidensis, a species able to use a wide variety of pathways for respiration, whose physiological reductant is unknown. Proteins with the FRD-like domain architecture are widely distributed among various bacteria that comprise a new type of water-soluble NADH:fumarate oxidoreductases. NADH:fumarate oxidoreductase (or FRD) from Klebsiella pneumoniae catalyses the anaerobic reduction of fumarate to succinate using NADH as the inherent electron donor . This entry includes Urocanate reductase (urdA) from Shewanella oneidensis, which catalyses the two-electron reduction of urocanate to dihydrourocanate and contains a FAD-binding domain homologous to the FAD-binding domains of succinate dehydrogenase and periplasmic fumarate reductase .
Tetrapyrrole biosynthesis, 5-aminolevulinic acid synthase (4pyrrol_synth_NH2levulA_synth)
Type: Domain

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway . The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin .

The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (

), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (

) to charge a tRNA with glutamate, glutamyl-tRNA reductase (

) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (

) to catalyse a transamination reaction to produce ALA.

The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase,

) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase,

) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (

) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.

Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (

). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (

) .

This entry represents 5-aminoaevulinic acid (ALA) synthase (

), which catalyses the first stage of tetrapyrrole biosynthesis by the C4 pathway, namely the condensation of succinyl CoA and glycine. ALA synthase is a pyridoxal-phosphate-dependent enzyme. During catalysis, glycine initially binds to the enzyme cofactor, and after condensation with succinyl CoA, CoA, carbon dioxide and 5-aminolevulinic acid are produced .
Putative 8-amino-7-oxononanoate synthase, Archaea/Firmicutes type (AONS_Archaea/Firmicutes)
Type: Family

This entry represents a group of putative 8-amino-7-oxononanoate synthases (AONS) mainly from Firmicutes and Archaea. They are related to the 8-amino-7-oxononanoate synthases from Proteobacteria (

), which is a pyridoxal 5'-phosphate-dependent enzyme that catalyses the decarboxylative condensation of L-alanine with pimeloyl-CoA to form 8(S)-amino-7-oxononanoate .
Poly(R)-hydroxyalkanoic acid synthase, class I (PHA_synth_I)
Type: Family

This entry represents the class I subfamily of poly(R)-hydroxyalkanoate synthases, which polymerises hydroxyacyl-CoAs with three to five carbons in the hydroxyacyl backbone into aliphatic esters termed poly(R)-hydroxyalkanoic acids. These polymers accumulate as carbon and energy storage inclusions in many species and can amount to 90 percent of the dry weight of the cell .
Peptidase M20A, peptidase V-related (M20A_pepV-rel)
Type: Family

This entry consists of Beta-Ala-Xaa dipeptidase (peptidase V, PepV) from Lactobacillus delbrueckii and other putative bacterial zinc dipeptidases belonging to the MEROPS peptidase family M20 (clan MH), subfamily M20A.

PepV, along with PepT, functions at the end of the proteolytic processing system. PepV is a monomeric metalloenzyme that preferentially degrades hydrophobic dipeptides. The Streptococcus gordonii PepV gene is homologous to the PepV gene family from Lactobacillus and Lactococcus spp. PepV recognizes and fixes the dipeptide backbone, while the side chains are not specifically probed and can vary, rendering it a nonspecific dipeptidase. It has been shown that Lactococcus lactis subspecies lactis (L9) PepV does not hydrolyze dipeptides containing Pro or D-amino acids at the C-terminal, while PepV from Lactobaccilus has been shown to have L-carnosine hydrolyzing activity .
HesB-related, selonoprotein (HesB-rel_seleno)
Type: Family

This entry represents a family of small proteins related to HesB and its close homologues, which are likely to be involved in iron-sulphur cluster assembly. Several members are selenoproteins, with a TGA codon and Sec residue that aligns to the conserved Cys of the HesB domain.
Na(+)-translocating NADH-quinone reductase subunit B (NqrB)
Type: Family

This entry represents the NqrB subunit of the six-protein (NqrA to NqrF), membrane-associated Na(+)-pumping NADH-quinone reductase of a number of marine and pathogenic Gram-negative bacteria . The Nqr complex catalyses the reduction of ubiquinone-1 to ubiquinol by two successive reactions, coupled with the transport of sodium ions from the cytoplasm to the periplasm. NqrA to NqrE are probably involved in the second step, the conversion of ubisemiquinone to ubiquinol. Both the NqrB and NqrC subunits contain a FMN cofactor that is covalently attached by a phosphate group to a threonine residue .
Na(+)-translocating NADH-quinone reductase subunit E (NqrE)
Type: Family

This entry represents the Na(+)-translocating E subunit from NADH:ubiquinone oxidoreductase. NADH can be oxidized by the respiratory chain of bacteria via NADH:quinone oxidoreductases that belong to three distinct enzyme families: NDH-1, NDH-2, and NQR. The NQR-type enzymes are sodium-motive NADH:quinone oxidoreductases consisting of six subunits (NqrA-F) and several cofactors: FAD, 2 FMN, a 2Fe-2S cluster and riboflavin. The NADH:quinone oxidoreductase activity of these enzymes is stimulated by sodium ions and is coupled with pumping of Na+ but not H+. Subunits NqrA, NqrC and NqrF represent the three major subunits of the NQR complex, which are alpha, gamma and beta, respectively. Subunits NqrB, NqrD and NqrE are very hydrophobic polypeptides that were found to co-localise with the alpha subunit .