SII-SWORD/CoKE huggingface dataset:
Polysaccharide export protein, N-terminal domain (Poly_export_N)
Type: Domain

This entry represents a domain found N-terminal in a group of bacterial polysaccharide export proteins, including Wza from Escherichia coli, which is likely to be involved in the export of the extracellular polysaccharide colanic acid (CA) from the cell to medium and Capsule polysaccharide export outer membrane protein CtrA from Neisseria meningitidis, which may function as a membrane anchor for capsular polysaccharides.
DNA-directed RNA polymerase, omega subunit (DNA-dir_RNA_pol_omega)
Type: Family

Bacterial DNA-dependent RNA polymerase (RNAP) has the core composition of α(2)-β-β'-omega, where omega is the smallest of the subunits. The omega subunit is required to promote RNAP assembly by acting like a chaperone to maintain beta' in the correct conformation and to recruit it to the α(2)β subassembly to form a functional core enzyme .
Recombination protein O, RecO (RecO)
Type: Family

The damage avoidance-tolerance pathway(s) requires functional recA, recF, recO, and recR genes, suggesting the mechanism to be daughter strand gap repair. The ruvABC genes or the recG gene is also required. The RecG pathway appears to be more active than the RuvABC pathway . RecO may contain a mononucleotide-binding fold .
OsmC/Ohr family (OsmC/Ohr_fam)
Type: Family

This family of peroxiredoxins includes osmotically inducible protein C (OsmC), a stress-induced protein found in Escherichia coli. This family also contains organic hydroperoxide resistance protein (Ohr), that has a novel pattern of oxidative stress regulation.

The transcription of the osmC gene of E. coli is regulated as a function of the phase of growth and is induced during the late exponential phase when the growth rate slows before entry into stationary phase. The transcription is initiated by two overlapping promoters, osmCp1 and osmCp2 .

Ohr from Xanthomonas campestris pv. phaseoli is highly induced by organic hydroperoxides, weakly induced by H2O2, and not induced at all by a superoxide generator. OHR may be a new type of organic hydroperoxide detoxification protein .
Phenazine biosynthesis PhzF-like (Phenazine_PhzF-like)
Type: Family

This entry represents the PhzF family, which includes PhzF and uncharacterised isomerases. PhzF is part of the seven-gene operon phzABCDEFG, responsible for the synthesis of phenazine-1-carboxylic acid (PCA) in Pseudomonas species . PhzF is a trans-2,3-dihydro-3-hydroxyanthranilate isomerase that catalyses the condensation of two molecules of trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) into the phenazine ring system. The final product is not yet known .
tRNA sulfurtransferase ThiI (tRNA_STrfase)
Type: Family

tRNA sulfurtransferase ThiI catalyses the ATP-dependent transfer of a sulfur to tRNA to produce 4-thiouridine in position 8 of tRNAs, which functions as a near-UV photosensor . In some bacteria, ThiI is a bifunctional enzyme required for the synthesis of both the 4-thiouridine modification in tRNA and the thiazole moiety in the thiamine biosynthesis pathway .

Three domains of ThiI are essential for the thiolation of tRNA: a THUMP domain that binds tRNA (see

) , an AANH domain (

) that activates the uridine residue by adenylylation , and a rhodanese-like domain (

) that transfers sulfur to the activated uridine residue . Neither the THUMP nor the AANH domain of ThiI are essential for thiamine synthesis, only the rhodanese domain is necessary for synthesis of the thiazole moiety of thiamine .
Pantoate-beta-alanine ligase (Pantoate_ligase)
Type: Family

D-Pantothenate is synthesized via four enzymes from ketoisovalerate, which is an intermediate of branched-chain amino acid synthesis . Pantoate-beta-alanine ligase, also know as pantothenate synthase, (PanC;

) catalyzes the formation of pantothenate from pantoate and alanine in the pantothenate biosynthesis pathway .

PanC belongs to a large superfamily of nucleotidyltransferases that includes ATP sulfurylase (ATPS), phosphopantetheine adenylyltransferase (PPAT), and the amino-acyl tRNA synthetases. The enzymes of this family are structurally similar and share a dinucleotide-binding domain .
Cobalamin biosynthesis precorrin-8X methylmutase CobH/CbiC (Cbl_synth_CobH/CbiC)
Type: Domain

This entry represents CbiC and CobH precorrin-8X methylmutase (

), both as stand-alone enzymes and when CobJ forms part of a bifunctional enzyme. CobH and CbiC from the aerobic and anaerobic pathways, respectively, catalyse a methyl rearrangement in precorrin-8 that moves the methyl group from C-11 to C-12 to produce hydrogenobyrinic acid . Hydrogenobyrinic acid now contains all the major framework alterations associated with corrin synthesis .

CobH and CbiC can sometimes be fused to other enzymes in the cobalamin pathway to make bifunctional enzymes: e.g., with CobJ/CibH and with CbiX.

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .
Precorrin-6x reductase (Precorrin-6x_reduct)
Type: Family

Cobalamins (vitamin B12), both as deoxyadenosylcobalamin and methylcobalamin, are involved as cofactors in a variety of enzymatic reactions and are synthesized by some bacteria and archaea. About thirty enzymes are required to manufacture cobalamins, some of the most complex nonpolymeric molecules biosynthesized in the cell. Cobalamin biosynthesis can be divided into three distinct sections. The first results in the synthesis of the corrin ring component, cobinamide, from the ubiquitous tetrapyrrole primogenitor uroporphyrinogen III by a series of reactions including eight S-adenosyl-L- methionine-dependent methylations, ring contraction, cobalt chelation, decarboxylation, amidations, and 1-amino-2-propanol attachment. The second results in the synthesis of the lower axial ligand, dimethylbenzimidazole (DMB) and the third results in the assembly of the final coenzyme from the attachment of the corrin ring to the DMB as well as the addition of the upper coordinating ligand for the cobalt, either an adenosyl or a methyl group .

The precorrin-6x reductase (

) proteins cobK and cbiJ are involved in part I of the cobalamin biosynthesis pathway. They catalyses the NADPH-dependent reduction of precorrin-6x to a dihydro derivative named precorrin-6y .
ATP:cob(I)alamin adenosyltransferase CobA/CobO/BtuR (CblAdoTrfase_CobA)
Type: Family

ATP:cob(I)alamin (or ATP:corrinoid) adenosyltransferases (

), catalyse the conversion of cobalamin (vitamin B12) into its coenzyme form, adenosylcobalamin (AdoCbl)or coenzyme B12 . AdoCbl contains an adenosyl moiety liganded to the cobalt ion of cobalamin via a covalent Co-C bond. AdoCbl is required as a cofactor for the activity of certain enzymes.

ATP:cob(I)alamin adenosyltransferases are classed into three groups: CobA-type , EutT-type and PduO-type . Each of the three enzyme types appears to be specialised for particular AdoCbl-dependent enzymes or for the de novo synthesis AdoCbl. PduO and EutT are distantly related, sharing short conserved motifs, while CobA is evolutionarily unrelated and is an example of convergent evolution.

This entry represents the ATP:cob(I)alamin adenosyltransferases CobA (Salmonella typhimurium), CobO (Pseudomonas aeruginosa), and BtuR (Escherichia coli). There is a high degree of sequence identity between these proteins . CobA is a homodimer responsible for attaching the adenosyl moiety from ATP to the cobalt ion of the corrin ring, necessary for the conversion of cobalamin to adenosylcobalamin .
Molybdenum-binding protein ModE, N-terminal (ModE-bd_N)
Type: Domain

This entry represents the N-terminal domain of the ModE protein. ModE is a molybdate-activated repressor of the molybdate transport operon in E. coli. It consists of the N-terminal domain represented by this entry and two tandem copies of mop-like domain, where Mop proteins are a family of 68-residue molybdenum-pterin binding proteins of Clostridium pasteurianum. Proteins containing this domain also includes a few archaeal proteins that lack Mop-like domains. PSI-BLAST analysis shows similarity to helix-turn-helix regulatory proteins .

Molybdenum-dependent repression of transcription of the Escherichia coli modABCD operon, which encodes the high-affinity molybdate transporter, is mediated by the ModE protein. When molybdate or tungstate bind to ModE there is little change in its α-helical content, but a major change in the environment of tryptophan and tyrosine residues occurs . This is the N-terminal domain of molybdenum-binding proteins ModE, ModA, MopA and MopB. These proteins are involved in molybdenum transport. ModE acts both as a repressor and activator of the mod and moa operons, respectively, depending on the properties of the binding site .
Homocysteine-binding domain (HCY_dom)
Type: Domain

The homocysteine (Hcy) binding domain is an ~300-residue module which is found in a set of enzymes involved in alkyl transfer to thiols:

Prokaryotic and eukaryotic B12-dependent methionine synthase (MetH) (

), a large, modular protein that catalyses the transfer of a methyl group from methyltetrahydrofolate (CH3-H4folate) to Hcy to form methionine, using cobalamin as an intermediate methyl carrier.

Mammalian betaine-homocysteine S-methyltransferase (BHMT) (

). It catalyses the transfer of a methyl group from glycine betaine to Hcy, forming methionine and dimethylglycine.

Plant selenocysteine methyltransferase ([ec:2.1.1.-]).

Plant and fungal AdoMet homocysteine S-methyltransferases (

).

The Hcy-binding domain utilises a Zn(Cys)3 cluster to bind and activate Hcy. It has been shown to form a (β/α)8 barrel. The Hcy binding domain barrel is distorted to form the metal- and substrate-binding sites. To accommodate the substrate, strands 1 and 2 of the barrel are loosely joined by nonclassic hydrogen bonds; to accommodate the metal, strands 6 and 8 are drawn together and strand 7 is extruded from the end of the barrel. The cysteines ligating the catalytic zinc atom are located at the C-terminal ends of strands 6 and 8 .
Ribosome maturation factor RimP (Ribosome_maturation_RimP)
Type: Family

The RimP protein (also known as YlxS in Bacillus subtilis) facilitates maturation of the 30S ribosomal subunit, and is required for the efficient production of translationally competent ribosomes .
Bifunctional nuclease domain (Bi_nuclease_dom)
Type: Domain

The bifunctional nuclease (BFN) domain is specific to bacteria and plant organisms. It has both RNase and DNase activities .

The dimer of the BFN domain forms a wedge, each monomer being a basic triangular shape. The BFN domain is composed of an eight-stranded, distorted β-sheet consisting of a four-stranded, antiparallel β-sheet (B1, B2, B3, B8), and a four-stranded mixed β-sheet (B4, B5, B6, B7). The sheets are intercalated by three short α-helices (H1, H3, H4), while a longer α-helix (H2) forms the central core of the dimer interface .

Some proteins known to contain a BFN domain are listed below:

Thermotoga maritima TM0160, a conserved hypothetical protein.

Plant bifunctional nuclease in basal defense response (BBD) proteins, regulators in abscisic acid (ABA)-mediated defense responses.

This entry represents the BFN domain.
Multi-copper polyphenol oxidoreductase (Cu_polyphenol_OxRdtase)
Type: Family

Laccases are multi-copper oxidoreductases able to oxidise a wide variety of phenolic and non-phenolic compounds and are widely distributed among both prokaryotes and eukaryotes. There are two main active catalytic sites with conserved histidines that are capable of binding four copper atoms .

This family consists of polyphenol oxidases with laccase activity from bacteria. They may constitute a new laccase subfamily, as they lack sequence relatedness to known laccases . This family also includes laccase domain-containing protein 1 (Lacc1, FAMIN), which is thought to be a central regulator of immunometabolic function in humans .
Dinitrogenase iron-molybdenum cofactor biosynthesis (Di-Nase_FeMo-co_biosynth)
Type: Domain

This entry represents several Nif (B, X and Y) proteins, which are involved in the biosynthesis of the iron-molybdenum cofactor (FeMo-co) found in the dinitrogenase enzyme of the nitrogenase complex in nitrogen-fixing bacteria. The nitrogenase complex catalyses the reduction of atmospheric dinitrogen to ammonia, and is composed of an iron metalloprotein (dinitrogenase reductase; homodimer of NifH;

) and a Fe-Mo metalloprotein (dinitrogenase; heterotetramer of NifD and NifK;

). The pathway for the synthesis of the Fe-Mo cofactor involves several proteins, including NifB, NifE, NifH, NifN, NifQ, NifV and NifX. NifB appears to be an iron-sulphur source for FeMo-co biosynthesis, while NifX may be associated with the mature FeMo-co, in particular with the addition of homocitrate during the last step of biosynthesis . The NifX protein shows sequence similarity with the C terminus of NifB , as well as to the conserved protein MTH1175 from the archaeon Methanobacterium thermoautotrophicum, which displays a ribonuclease H-like motif of three layers, α/β/α, with a single mixed β-sheet .
D-aminoacyl-tRNA deacylase DTD (Daa-tRNA_deacyls_DTD)
Type: Family

This family consists of D-aminoacyl-tRNA deacylase DTD, also known as D-Tyr-tRNA(Tyr) deacylase. It is an enzyme that cleaves misacetylated D-aminoacyl-tRNA molecules into free tRNAs and D-amino acids . Cell growth inhibition by several D-amino acids can be explained by an in vivo production of D-aminoacyl-tRNA molecules.

The enzyme is found in bacteria and in eukaryotes but not in archaea. It has a β-barrel-like fold structure and forms homodimers in which two surface cavities serve as the active site for tRNA binding .
Domain of unknown function DUF155 (DUF155)
Type: Domain

This entry represents a domain found in RMND1 from mammals, Sif2/Sif3 from fission yeasts and Rmd1/Rmd8/YDR282C (Mrx10) from budding yeasts.

RMND1 and its yeast homologue, Mrx10, are mitochondrial proteins required for mitochondrial translation .
Metal-sensitive transcriptional repressor (Metal_Tscrpt_repr)
Type: Family

This is a family of metal-sensitive repressors, involved in resistance to metal ions. Members of this family bind copper, nickel or cobalt ions via conserved cysteine and histidine residues. In the absence of metal ions, these proteins bind to promoter regions and repress transcription. When bound to metal ions they are unable to bind DNA, leading to transcriptional derepression .
Phenylacetic acid degradation-related domain (PAAI_dom)
Type: Domain

This domain is found in the PAAI protein from Escherichia coli that may be involved in phenylacetic acid degradation and in a few others that may be transcription regulators . Most proteins containing this domain consist almost entirely of a single copy of this domain. A protein from Caenorhabditis elegans consists of two tandem copies of the domain. The domain is also found as the N-terminal region of an apparent initiation factor eIF-2B alpha subunit of Aquifex aeolicus.
N-acetylglucosaminyl phosphatidylinositol deacetylase-related (GlcNAc_PI_deacetylase-related)
Type: Family

Members of this family include N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase (

) that catalyses the second step in glycosylphosphatidylinositol (GPI) biosynthesis and 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (

), involved in the biosynthesis of mycothiol (an unusual thiol compound found in Actinobacteria) .
SOS response associated peptidase (SRAP) (SRAP)
Type: Family

The SRAP (SOS-response associated peptidase) family is characterised by the SRAP domain with a novel thiol autopeptidase activity, whose active site in human HMCES is comprised of the catalytic triad residues C2, E127, and H210 . SRAP proteins are evolutionarily conserved in all domains of life. For instance, human HMCES and E. coli YedK are similar in both sequence and structure . HMCES was originally identified as a possible reader of 5hmC in embryonic stem cell extracts using a double-stranded DNA molecule containing 5hmC as bait . The bacterial members have operonic associations with the SOS DNA damage response, mutagenic translesion DNA polymerases, non-homologous DNA-ending-joining networks that employ Ku and an ATP-dependent ligase, and other repair systems .
Lysine-2,3-aminomutase/glutamate 2,3-aminomutase (Lys_aminomutase/Glu_NH3_mut)
Type: Family

This entry represents the lysine-2,3-aminomutase (LAM) family of proteins. LAM catalyses the interconversion of L-alpha-lysine and L-beta-lysine, which proceeds by migration of the amino group from C2 to C3 concomitant with cross-migration of the 3-pro-R hydrogen of L-alpha-lysine to the 2-pro-R position of L-beta-lysine. Glutamate 2,3-aminomutase is closely related to LAM, but can be distinguished by architecture (longer N-terminal region, shorter C-terminal region) and replacement of key lysine-binding residues . Glutamate 2,3-aminomutase catalyses the interconversion of L-glutamate and L-beta-glutamate .
Uncharacterised membrane protein YitT (YitT)
Type: Family

This entry includes proteins with transmembrane domains, such as YitT from Bacillus subtilis. The function of YitT is not clear.
LUD domain (LUD_dom)
Type: Domain

This entry represents a domain found in lactate utilization proteins B (LutB) and C (LutC), as well as several uncharacterised proteins. LutB and LutC are encoded by the conserved LutABC operon in bacteria. They are involved in lactate utilization and is implicated in the oxidative conversion of L-lactate into pyruvate . Proteins containing this domain also include DVU3032 from Desulfovibrio. From the results of the genetic and biochemical experiments, DVU3032 has been predicted as a lactate dehydrogenase .
RNA methyltransferase RlmH (RlmH-like)
Type: Family

Methyltransferases (Mtases) are responsible for the transfer of methyl groups between two molecules. The transfer of the methyl group from the ubiquitous S-adenosyl-L-methionine (AdoMet) to nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms. The reactions are catalysed by Mtases and modify DNA, RNA, proteins or small molecules, such as catechol, for regulatory purposes. Members of this family are predicted to be Mtases based on the crystal structure (1TO0) and its close structural homology to other structures (1VHK,1MXI,1IPA,1K3R) that have methyltransferase activity .
C4-type zinc ribbon domain (Zf-RING_7)
Type: Domain

This entry represents a Zn-ribbon domain rich in aromatic and positively charged amino acid residues. This C-terminal Zn-ribbon domain consists of two β-strands acting as a scaffold for the two Zn knuckles. Both pairs of cysteines making up the two Zn knuckles are situated at highly conserved sharp β-turns, an arrangement that facilitates the tetrahedral coordination of the divalent Zn ion. The two Zn-knuckle cysteine motifs are separated by 20 residues, 9 of which form an α-helix (helix 4) .Structural modelling suggests this domain may bind nucleic acids . The domain appears to bind flaA-mRNA, thus contributing to flagellum formation and motility .
Queuosine precursor transporter (YhhQ)
Type: Family

This entry includes queuosine (Q) precursor transporter from
Escherichia coli
, which is required for the import and rescue of the queuosine precursors 7-cyano-7-deazaguanine (preQ0) and 7-aminomethyl-7-deazaguanine (preQ1) . Membranes are impermeable to purines; therefore, transporters are required for the salvage of Q precursors.
Protein of unknown function DUF166 (DUF166)
Type: Family

This family had been implicated to catalyse the synthesis of thymidine monophosphate (dTMP) from deoxyuridine monophosphate (dUMP). The physiological co-substrate has not yet been identified . Previous designation of this famliy as being thymidylate synthase from one paper, has been suggested to be erroneous .

A member of this family from Methanococcus maripaludis was found to be important for fitness during autotrophic growth and may have an accessory role in carbon dioxide assimilation .
Protein of unknown function DUF167 (DUF167)
Type: Family

This entry describes a group of proteins of unknown function found in all cellular organisms. Structures for two of these proteins, YggU from Escherichia coli and MTH637 from the archaea Methanobacterium thermoautotrophicum, have been determined; they have a core 2-layer α/β structure consisting of β(2)-loop-α-β(2)-α structural elements .
Protein of unknown function DUF169 (DUF169)
Type: Family

This entry describes proteins of unknown function.
Sulfur carrier ThiS/MoaD-like (ThiS/MoaD-like)
Type: Family

ThiS (thiaminS) is a 66 aa protein involved in sulphur transfer. ThiS is coded in the thiCEFSGH operon in Escherichia coli. This family of proteins have two conserved Glycines at the COOH terminus. Thiocarboxylate is formed at the last G in the activation process. Sulphur is transferred from ThiI to ThiS in a reaction catalysed by IscS . MoaD, a protein involved in sulphur transfer during molybdopterin synthesis, is about the same length and shows limited sequence similarity to ThiS. Both have the conserved GG at the COOH end .

ThiS/MoaD proteins serve as sulfur carriers in thiamine and tungsten/molybdenum cofactor biosynthesis. Proteins in this entry also include TtuB from Thermus thermophilus. TtuB functions as the sulfur donor in the sulfurtransferase reaction catalyzed by TtuA . It is also required for the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine (m5s2U or s2T). This modification allows thermal stabilization of tRNAs in thermophilic microorganisms, and is essential for cell growth at high temperatures .
Putative RNA methyltransferase C9orf114-like (Put_MeTrfase-C9orf114-like)
Type: Family

This entry includes the putative methyltransferase C9orf114 from human, also known as SPOUT1, and its homologues . It is required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase . It is also involved in chromosome alignment . SPOUT1 binds specifically to miRNA MIR145 hairpin and regulates MIR145 expression at a postranscriptional level .

Members of this family have a TIM barrel-like fold with a deep C-terminal trefoil knot. The arrangement of its hydrophilic and hydrophobic surfaces are opposite to that of the classic TIM barrel proteins.
Translational regulator CsrA (CsrA)
Type: Family

The RNA-binding protein CsrA (carbon storage regulator) is a new kind of global regulator, which facilitates specific mRNA decay . CsrA is entirely contained within a globular complex of approximately 18 CsrA-H6 subunits and a single RNA, CsrB. CsrA binds to the CsrB RNA molecule to form the Csr regulatory system which has a strong negative regulatory effect on glycogen biosynthesis, glyconeogenesis and glycogen catabolism and a positive regulatory effect on glycolysis .