SII-SWORD/CoKE huggingface dataset:
Glycophorin-binding protein (Glycophorin-bd)
Type: Repeat

The glycophorin-binding protein contains a tandem repeat. The repeated sequence determines the binding domain for an erythrocyte receptor binding protein of Plasmodium falciparum, the malarial parasite . Erythrocyte invasion by the malarial merozoite is a receptor-mediated process, an obligatory step in the development of the parasite. The P. falciparum protein binds to the erythrocyte receptor glycophorin.
rRNA small subunit methyltransferase G (rRNA_ssu_MeTfrase_G)
Type: Family

This entry represents a rRNA small subunit methyltransferase G. Previously identified as a glucose-inhibited division protein B that appears to be present and in a single copy in all complete eubacterial genomes so far sequenced. Specifically methylates the N7 position of a guanosine in 16S rRNA .
Cytochrome b6/f complex, subunit 5 (Cyt_6/f_cplx_su5)
Type: Family

This family consists of cytochrome b6/f complex subunit 5 (PetG). The cytochrome bf complex, found in green plants, eukaryotic algae and cyanobacteria, connects photosystem I to photosystem II in the electron transport chain, functioning as a plastoquinol:plastocyanin/cytochrome c6 oxidoreductase . The purified complex from the unicellular alga Chlamydomonas reinhardtii contains seven subunits; namely four high molecular weight subunits (cytochrome f, Rieske iron-sulphur protein, cytochrome b6, and subunit IV) and three approximately miniproteins (PetG, PetL, and PetX) . Stoichiometry measurements are consistent with every subunit being present as two copies per b6/f dimer. The absence of PetG affects either the assembly or stability of the cytochrome bf complex in C. reinhardtii .
Porin, alpha proteobacteria type (Porin_alphabac)
Type: Family

This family consists of porins from the alpha subdivision of Proteobacteria. Members of this family are related to Gram-negative porins , including Porin Omp2a/b from Brucella . The porins form large aqueous channels in the cell membrane allowing the selective entry of hydrophilic compounds this so called 'molecular sieve' is found in the cell walls of Gram-negative bacteria.
Photosystem I PsaD (PsaD)
Type: Family

PsaD is a small, extrinsic polypeptide located on the stromal side (cytoplasmic side in cyanobacteria) of the photosystem I reaction centre complex. It is required for native assembly of PSI reaction clusters and is implicated in the electrostatic binding of ferredoxin within the reaction centre . PsaD forms a dimer in solution which is bound by PsaE however PsaD is monomeric in its native complexed PSI environment .
Photosystem II PsbI (PSII_PsbI)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This entry represents the low molecular weight transmembrane protein PsbI, which is tightly associated with the D1/D2 heterodimer in PSII. The function of PsbI is unknown, but it may be involved in the assembly, dimerisation or stabilisation of PSII dimers .
Photosystem II PsbK (PSII_PsbK)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This entry represents the low molecular weight transmembrane protein PsbK found in PSII, where it is tightly associated with the antenna protein CP43 (PsbC). PsbK is required for accumulation of the PSII complex, and may participate in the assembly and stability of the PSII complex. In particular, PsbK may be involved in the binding of plastoquinone and in maintaining the dimeric organisation of PSII .
Type IV secretion system protein TraG/VirD4 (TraG/VirD4)
Type: Family

This entry represents type IV secretion system proteins TraG and VirD4. TraG-like proteins are potential NTP hydrolases (NTPases) that are essential for DNA transfer in bacterial conjugation. They are thought to mediate interactions between the DNA-processing (Dtr) and the mating pair formation (Mpf) systems . TraG-like proteins also function as essential components of type IV secretion systems of several bacterial pathogens. TraG is essential for DNA transfer in bacterial conjugation . Agrobacterium tumefaciens VirD4 is essential for DNA transfer to plants . VirD has been shown to have topoisomerase activity
in vitro
.
Zinc/iron permease (ZIP)
Type: Family

The ZIP family consists of zinc transport proteins and many putative metal transporters found in al cellular organisms, including the Arabidopsis thaliana ZIP protein family which is responsible for zinc uptake in the plant . ZIP proteins play essential roles in metal metabolism/homeostasis and are widely involved in numerous physiological and pathological processes.

The crystal structure of a ZIP from Bordetella bronchiseptica showed eight transmembrane helices (TMs) forming a tightly associated helix bundle, where four TMs create an inner bundle surrounded by the other four TMs and a a binuclear metal centre (BMC) is harboured in the transport pathway . The two associated metal binding sites in the BMC play different roles: one of them is the key transport site, whereas the other, the auxiliary site, is required not only to achieve maximal zinc transport activity but also to maintain a uniform activity in a broad pH range .

ZIP4, a human member of this family, is related to a rare autosomal recessive disease caused by the inability to absorb sufficient zinc . ZIPCO, a Plasmodium member, has a crucial role in the parasite liver-stage development .
Transcription termination factor, mitochondrial/chloroplastic (MTERF)
Type: Family

This entry represents the mitochondrial/chloroplastic transcription termination factors (MTERFs). In humans, four MTERFs have been identified (MTERF1-4). MTERF1 was first identified as a factor responsible for terminating heavy strand transcription at a specific site at the leu-tRNA, thereby modulating the ratio of mitochondrial ribosomal RNA to mRNA . Later, MTERF1 was found to stimulate transcriptional initiation and appeared to be in the control of mitochondrial replication pausing . From a structural study, it binds to dsDNA containing the termination sequence and unwinds the DNA molecule, promoting base eversion, which is critical for transcription termination .
Fluoride-specific ion channel FluC (FluC)
Type: Family

FluC, also known as CrcB, is an integral membrane protein that acts as an efflux transporter which confers resistance to fluoride ion, thus reducing its toxicity . It is highly specific for fluoride ions and cannot transport chloride ions . Over expression in E. coli leads to camphor resistance .
Hydantoinase B/oxoprolinase (Hydantoinase_B)
Type: Domain

An appreciable fraction of the sulphur present in mammals occurs in the form of glutathione. The synthesis of glutathione and its utilization take place by the reactions of the gamma-glutamyl cycle, which include those catalysed by gamma-glutamylcysteine and glutathione synthetases, gamma-glutamyl transpeptidase, cysteinylglycinase, gamma-glutamyl cyclotransferease, and 5-oxoprolinase .

This domain is found in N-methylhydantoinase B, which converts hydantoin to N-carbamyl-amino acids, and in 5-oxoprolinase

which catalyses the formation of L-glutamate from 5-oxo-L-proline. These enzymes are part of the oxoprolinase family.
NAD(+) synthetase (NAD_synthase)
Type: Family

This entry represents NAD(+) synthetases, including glutamine-dependent NAD(+) synthetases and NH(3)-dependent NAD(+) synthetases.

NAD+ is involved electron transport and redox reactions and in DNA ligation and protein ADP-ribosylation. In yeast and most other organisms, NAD is generated through the de novo pathway and the salvage pathway. In the de novo pathway, quinolinic acid is converted to nicotinic acid mononucleotide (NaMN). In the salvage pathway, NaMN is generated by recycling of nicotinamide. Both pathways converge on NaMN, which is then converted into deamido-NAD+. Subsequently, deamido-NAD+ is converted to NAD+ by NAD+ synthetase .

NAD+ synthetase has been extensively studied in bacteria. It is encoded by nadE gene in E. coli and by outB gene in B. subtilis . These prokaryotic enzymes are ammonia-dependent (containing an ammonia-utilising domain). However, some pokaryotic NAD(+) synthetases, such as that from Mycobacterium tuberculosis, contain a nitrilase-related domain, are glutamine-dependent .
Ppx/GppA phosphatase, N-terminal (Ppx_GppA_N)
Type: Domain

This entry represents the N-terminal domain of Exopolyphosphate phosphatase (Ppx)

and guanosine pentaphosphate phosphatase (GppA)

, which belong to the sugar kinase/actin/hsp70 superfamily .
Carbamoyltransferase (Carbtransf_dom)
Type: Domain

This domain is found in NodU from Rhizobium, CmcH from Nocardia lactamdurans and the bifunctional carbamoyltransferase TobZ from Streptoalloteichus tenebrarius. NodU a Rhizobium nodulation protein involved in the synthesis of nodulation factors has 6-O-carbamoyltransferase-like activity . CmcH is involved in cephamycin (antibiotic) biosynthesis and has 3-hydroxymethylcephem carbamoyltransferase activity (

) . TobZ functions as an ATP carbamoyltransferase and tobramycin carbamoyltransferase .
Nucleoside triphosphate pyrophosphatase Maf-like protein (Maf-like)
Type: Family

The Maf protein of Bacillus subtilis shares substantial amino acid sequence identity with Escherichia coli YhdE (previously known as OrfE) . Maf-like proteins are conserved in bacteria, archaea, and eukaryotes. Maf proteins have been implicated in cell division arrest . It has also been proposed that they belong to a family of house-cleaning nucleotide hydrolyzing enzymes which prevent the incorporation of noncanonical nucleotides into cellular DNA . Maf proteins exhibit nucleotide pyrophosphatase activity against canonical and modified nucleotides, which might represent a molecular mechanism for this dual role in cell division arrest and in house-cleaning .

This entry includes pyrophosphatases, such as YhdE and YceF from E. coli. YhdE is a nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP . YceF is a nucleoside triphosphate pyrophosphatase that hydrolyzes 7-methyl-GTP (m7GTP) .
Lipoyl synthase (Lipoyl_synth)
Type: Family

Lipoyl synthase is an iron-sulphur protein . It is localised to mitochondria in yeast and Arabidopsis . It generates lipoic acid, a thiol antioxidant that is linked to a specific Lys as prosthetic group for the pyruvate and alpha-ketoglutarate dehydrogenase complexes and the glycine-cleavage system.
S-adenosylmethionine:tRNA ribosyltransferase-isomerase, QueA (QueA)
Type: Family

This entry represents the S-adenosylmethionine:tRNA ribosyltransferase-isomerase, QueA. Queuosine is a hypermodified nucleoside that usually occurs in the first position of the anticodon of tRNAs specifying the amino acids asparagine, aspartate, histidine, and tyrosine. The hypermodified nucleoside is found in bacteria and eukaryotes . Queuosine is synthesized
de novo
exclusively in bacteria; for eukaryotes the compound is a nutrient factor. Queuosine biosynthesis protein, or S-adenosylmethionine:tRNA-ribosyltransferase-isomerase (QueA) catalyses the formation of the 2,3-epoxy-4,5-dihydroxycyclopentane ring of the Q precursor epoxyqueuosine (oQ). S-adenosyl-L-methionine (AdoMet) reacts with 7-aminomethyl-7-deazaguanine of tRNA at position 34 to yield adenine, methionine, and a modified tRNA with oQ at position 34.

QueA consists of two domains: domain 1 has three layers (α/β/α)), while domain 2 is a closed β-barrel with Greek-key topology .
Ketopantoate hydroxymethyltransferase (Pantoate_hydroxy_MeTrfase)
Type: Family

The panB gene from Escherichia coli encodes the first enzyme of the pantothenate biosynthesis pathway, ketopantoate hydroxymethyltransferase (KPHMT)

. Fungal ketopantoate hydroxymethyltransferase is essential for the biosynthesis of coenzyme A, while the pathway intermediate 4'-phosphopantetheine is required for penicillin production .
DNA double-strand break repair protein Mre11 (Mre11)
Type: Family

Mre11 and Rad50 are two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50 .
Acetyl-CoA hydrolase/transferase, N-terminal (ActCoA_hydro_N)
Type: Domain

This entry represents an acetyl-CoA hydrolase/transferase N-terminal domain. This domain is found in several enzymes which take part in pathways involving acetyl-CoA, including acetyl-CoA hydrolase

, propionyl-CoA:succinate CoA transferase, succinyl-CoA:coenzyme A transferase (CAT1) and 4-hydroxybutyrate coenzyme A transferase (CAT2)

.

Acetyl-CoA hydrolase catalyses the formation of acetate from acetyl-CoA , Succinyl-CoA:coenzyme A transferase (CAT1) produces succinyl-CoA, and propionyl-CoA:succinate CoA transferase transfer of coenzyme A from propionyl-CoA to succinate .
Acyl-CoA thioesterase (Acyl_CoA_thio)
Type: Family

Acyl-CoA thioesterases are a group of enzymes that catalyse the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH). They consequently have the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. They may also be involved in the metabolic regulation of peroxisome proliferation.

This family includes Acyl-CoA thioesterase 2 from gammaproteobacteria , Acyl-coenzyme A thioesterase 8 from mammals , Peroxisomal acyl-coenzyme A thioester hydrolase 1 from Saccharomyces cerevisiae and Acyl-CoA hydrolase 1/2 from Arabidopsis thaliana .
Acetyl-CoA decarbonylase/synthase complex subunit epsilon (CdhB)
Type: Family

The ACDS complex contains five subunits, among which beta possesses an Ni-Fe-S active-site metal cluster, the A-cluster, at which reaction with acetyl-CoA takes place, generating an acetyl-enzyme species poised for C-C bond cleavage . The ACDS complex is made up of alpha, epsilon, beta, gamma and delta chains with a probable stoichiometry of (alpha(2)epsilon(2))(4)-beta(8)-(gamma(1)delta(1))(8).

This entry represents the epsilon subunit.

Acetyl-CoA decarbonylase/synthase (ACDS) is a 5-subunit-containing multienzyme complex found exclusively in methanogens and certain other Archaea . ACDS catalyses the central reaction of acetyl C-C bond cleavage in methanogens growing on acetate and is also responsible for synthesis of acetyl units during growth on C-1 substrates .
Cobalt transport protein CbiN (CbiN)
Type: Family

The cobalt transport protein CbiN is part of the active cobalt transport system involved in uptake of cobalt in to the cell involved with cobalamin biosynthesis (vitamin B12). It has been suggested that CbiN may function as the periplasmic binding protein component of the active cobalt transport system .
CstA, N-terminal domain (CstA_N)
Type: Domain

Escherichia coli induces the synthesis of at least 30 proteins at the onset of carbon starvation, two-thirds of which are positively regulated by the cyclic AMP (cAMP) and cAMP receptor protein (CRP) complex. Proteins in this entry include carbon starvation protein CstA, which is a predicted membrane protein that may be involved in peptide utilisation . This entry represents the N-terminal domain of CstA.
Bacterial protein export chaperone SecB (SecB)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion .

The tertiary structure of Haemophilus influenzae SecB (

) was resolved by means of X-ray crystallography to 2.5A . The chaperone comprises four chains, forming a tetramer, each chain of which has a simple α+β fold arrangement. While one binding site on the homotetramer recognises unfolded polypeptides by hydrophobic interactions, the second binds to SecA through the latter's C-terminal 22 residues.
D-alanyl-D-alanine carboxypeptidases DD-CPases, core domain (DD-CPase_core_dom)
Type: Domain

This entry represents the common core domain found in D-alanyl-D-alanine carboxypeptidases (DD-CPases) and related proteins mostly found in bacteria. This domain features a central twisted antiparallel β-sheet (β1-β6) flanked by two pairs of three α-helices (α2, α3, α6, and α1, α5, α7) on the two faces of the β-sheet .

Carboxypeptidase YodJ, a specific DD-CPase, plays a role in peptidoglycan maturation and spore development. It releases D-Ala from peptidoglycan precursors, affecting substrate availability for crosslinking and modulating spore resistance and germination .

The VanX protein, a D-alanyl-D-alanine dipeptidase, is crucial in vancomycin resistance mechanisms. It hydrolyzes D-Ala-D-Ala dipeptides, reducing the availability of vancomycin-binding targets in the cell wall .

The bifunctional VanXYC protein combines D-Ala-D-Ala dipeptidase and D-Ala-D-Ala carboxypeptidase activities. This dual functionality allows for efficient modification of peptidoglycan precursors, contributing to vancomycin resistance in some bacterial strains .

D-alanyl-D-alanine carboxypeptidases (DD-CPases) are bacterial enzymes crucial for cell wall biosynthesis and peptidoglycan remodeling. These enzymes belong to the penicillin-binding protein (PBP) family and are inhibited by β-lactam antibiotics . DD-CPases catalyze the removal of terminal D-alanine from peptidoglycan precursors, influencing cell wall structure, antibiotic resistance, and spore formation .
Ketopantoate reductase ApbA/PanE (ApbA)
Type: Family

ApbA, the ketopantoate reductase enzyme

of Salmonella typhimurium is required for the synthesis of thiamine via the alternative pyrimidine biosynthetic pathway . Precursors to the pyrimidine moiety of thiamine are synthesized de novo by the purine biosynthetic pathway or the alternative pyrimidine biosynthetic (APB) pathway. The ApbA protein catalyzes the NADPH-specific reduction of ketopantoic acid to pantoic acid. This activity had previously been associated with the pantothenate biosynthetic gene panE . ApbA and PanE are allelic .

This entry also include budding yeast Pan5, which is a 2-dehydropantoate 2-reductase involved in the (R)-pantothenate biosynthesis .
CarD-like/TRCF, RNAP-interacting domain (CarD-like/TRCF_RID)
Type: Domain

This is the RNA polymerase-interacting domain (RID) superfamily of transcription-repair-coupling factor (TRCF), CarD and CarD homologue in Myxococcus xanthus, called CdnL . CarD is a Myxococcus xanthus protein required for the activation of light- and starvation-inducible genes . Furthermore, CarD is widely distributed among bacteria and represents a distinct class of RNAP binding proteins that regulate transcription and essential processes. TRCF couples transcription and DNA repair in bacteria in which the RID domain is essential for the RNAP release function .

The structure of CarD presents a partly open barrel (tudor-like) topology. The last strand is interrupted by a turn of 3-10 helix.
Cyanate lyase, C-terminal (Cyanate_lyase_C)
Type: Domain

Some bacteria can overcome the toxicity of environmental cyanate by hydrolysis of cyanate. This reaction is catalyzed by cyanate lyase (also known as cyanase) . Cyanate lyase is found in bacteria and plants and catalyzes the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide.

The cyanate lyase monomer is composed of two domains. The N-terminal domain shows structural similarity to the DNA-binding α-helix bundle motif. The C-terminal domain has an 'open fold' with no structural homology to other proteins. The dimer structure reveals the C-terminal domains to be intertwined, and the decamer is formed by a pentamer of these dimers. The active site of the enzyme is located between dimers and is comprised of residues from four adjacent subunits of the homodecamer .
Flagellar protein FliS (FliS)
Type: Family

The fliD operon of several bacteria consists of three flagellar genes, fliD, fliS, and fliT, and is transcribed in this order . In Bacillus subtilis the operon encoding the flagellar proteins FliD, FliS, and FliT is sigma D-dependent .

FliS is a flagellin-specific T3S chaperone that binds in 1:1 stoichiometry to the C-terminal region of flagellin and facilitates its export, preventing polymerization in the cytoplasm . The fliS gene is necessary for flagellation. In Aeromonas, deletion of this gene (called flaJ) resulted in the complete loss of motility, flagellin expression, and adherence .
PhoH-like protein (PhoH)
Type: Domain

PhoH is a cytoplasmic protein and predicted ATPase that is induced by phosphate starvation and belongings to the phosphate regulon (pho) in Escherichia coli .