SII-SWORD/CoKE huggingface dataset:
6-phosphogluconate dehydrogenase, domain 2 (6PGD_dom2)
Type: Homologous_superfamily

This superfamily represents a multi-helical domain found in several NAD or NADP-utilizing dehydrogenases, including 6-phosphogluconate dehydrogenase , classes I and II ketol-acid reductoisomerases , L-3-hydroxyacyl CoA dehydrogenase , UDP-glucose dehydrogenase , glycerol-3-phosphate dehydrogenase , ketopantoate reductase , N-(1-D-carboxylethyl)-L-norvaline dehydrogenase , and mannitol 2-dehydrogenase . This domain, often found in the C-terminal region of the sequence, is also found in some Cytokine-like nuclear factor N-PAC proteins, which have chromatin gene reader activity involved in chromatin modification and regulation of gene expression in humans .
Ketopantoate reductase, N-terminal domain (KPR_N)
Type: Domain

Ketopantoate reductase catalyses the NADPH-dependent reduction of ketopantoate to pantoate on the pantothenate (vitamin B5) biosynthetic pathway. This entry represents the N-terminal domain of ketopantoate reductase. ketopantoate reductase. It has an alphabeta-fold of the Rossmann type .
Ryanodine receptor (Ryan_recept)
Type: Family

Ryanodine receptors are involved in communication between transverse-tubules and the sarcoplamic reticulum of cardiac and skeletal muscle. The proteins function as a Ca
2+
-release channels following depolarisation of transverse-tubules . The function is modulated by Ca
2+
, Mg2+, ATP and calmodulin. Deficiency in the ryanodine receptor may be the cause of malignant hyperthermia (MH) and of central core disease of muscle (CCD) . MH is an autosomal dominant disorder of skeletal muscle and is a principal cause of death due to anaesthesia.

Calcium release activity of the receptors resides in the C-terminal region of the protein, the remaining part of the molecule forming a 'foot' structure that spans the junctional gap between the sarcoplamic reticulum and the transverse-tubule. The foot structure may interact with the cytoplasmic region of the dihydropyridine receptor.

Analysis of the sequence reveals 10 potential transmembrane (TM) regions in the C-terminal fifth of the molecule and 2 further potential TM regions nearer to the centre . These may contribute to the formation of the Ca
2+
conducting pore. The rest of the sequence is hydrophilic, and presumably constitutes the cytoplasmic domain of the protein.
Trp repressor, bacterial (Trp_repress_bac)
Type: Family

The Trp repressor (TrpR) binds to at least five operators in the Escherichia coli genome, repressing gene expression. The operators at which it binds vary considerably in DNA sequence and location within the promoter; when bound to the Trp operon it recognises the sequence 5'-ACTAGT-3' and acts to prevent the initiation of transcription. The TrpR controls the trpEDCBA (trpO) operon and the genes for trpR, aroH, mtr and aroL, which are involved in the biosynthesis and uptake of the amino acid tryptophan . The repressor binds to the operators only in the presence of L-tryptophan, thereby controlling the intracellular level of its effector; the complex also regulates Trp repressor biosynthesis by binding to its own regulatory region. TrpR acts as a dimer that is composed of identical 6-helical subunits, where four of the helices form the core of the protein and intertwine with the corresponding helices from the other subunit.

This entry represents Trp repressors found in proteobacterial and chlamydial species.
CRISPR-associated protein Cas5, Tneap type (CRISPR-assoc_prot_Cas5_Tneap)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the Cas5 family of proteins (Tneap-type), which includes TM1800 from Thermotoga maritima . Cas5 is found within a cluster of three cas genes associated with CRISPR structures in many bacterial species, named cas1B, cas5 and cas6 .,
Mandelate racemase/muconate lactonizing enzyme, N-terminal domain (Mandelate_racemase_N_dom)
Type: Domain

This entry represents a domain found towards the N-terminal region of mandelate racemase and muconate lactonizing enzyme. These enzymes share a bidomain structure containing a capping domain and a C-terminal barrel domain. The N-terminal domain forms part of the capping domain .
Mandelate racemase/muconate lactonizing enzyme, C-terminal (Mandelate_racemase_C)
Type: Domain

Mandelate racemase

(MR) and muconate lactonising enzyme

(MLE) are two bacterial enzymes involved in aromatic acid catabolism. They catalyse mechanistically distinct reactions yet they are related at the level of their primary, quaternary (homooctamer) and tertiary structures . A number of other proteins also seem to be evolutionary related to these two enzymes. These include, various plasmid-encoded chloromuconate cycloisomerases

, Escherichia coli protein rspA , E. coli bifunctional DGOA protein, a number of D-galactonate dehydratases and D-mannonate dehydratases, and a hypothetical protein from Streptomyces ambofaciens .

This entry represents the C-terminal region of these proteins.
CRISPR-associated protein Cas4 (CRISPR-assoc_prot_Cas4)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the Cas4 family of proteins. Cas4 proteins resembles the RecB family of exonucleases (

) and contains a cysteine-rich motif indicative of DNA binding. As such, Cas4 proteins may function as part of a hypothetical DNA repair system . Cas4 from the archaeon Sulfolobus solfataricus has been shown to be a 5' to 3' single stranded DNA exonuclease in vitro, and to contain an iron-sulfur cluster .

Cas4 is one of four protein families (Cas1 to Cas4) that are associated with CRISPR elements and always occur near a repeat cluster, usually in the order cas3-cas4-cas1-cas2.
Ribonucleotide reductase, adenosylcobalamin-dependent (RNR_NrdJ/NrdZ)
Type: Family

Ribonucleotide reductase (also known as ribonucleoside-diphosphate reductase) catalyses the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides providing the precursors necessary for DNA synthesis. Three main classes of ribonucleotide reductases (RNR) have been discovered that depend on different metal cofactors for the catalytic activity: class I enzymes contain a diiron-oxygen cluster, class II a cobalt containing cobalamin cofactor (vitamin B12), and class III an 4Fe-4S iron-sulfur cluster coupled to S-adenosylmethionine (SAM) .

This entry represents a group of adenosylcobalamin (AdoCbl or coenzymeB12)-dependent ribonucleotide reductases (Class II RNRs) related to the characterised species from Pyrococcus , Thermoplasma , Corynebacterium and Deinococcus . RNR's are responsible for the conversion of the ribose sugar of RNA into the deoxyribose sugar of DNA. This is the rate-limiting step of DNA biosynthesis. This model identifies genes in a wide range of deeply branching bacteria. All are structurally related to the class I (non-haem iron-dependent) RNRs. In most species this gene is known as NrdJ, while in mycobacteria it is called NrdZ.
Ribonucleoside-triphosphate reductase, adenosylcobalamin-dependent (RTP_Rdtase_AdoCbl-dep)
Type: Family

This entry represents a group of adenosylcobalamin (AdoCbl or coenzymeB12)-dependent ribonucleotide reductases (RNR) related to the characterised species from Lactococcus leichmannii . RNR's are responsible for the conversion of the ribose sugar of RNA into the deoxyribose sugar of DNA. This is the rate-limiting step of DNA biosynthesis. This model identifies NrdJ enzymes only in cyanobacteria, Lactococcus and certain bacteriophages. A separate model (

) identifies a larger group of divergent B12-dependent RNR's.
Ribonucleotide reductase, class I, alpha subunit, C-terminal (NrdE_NrdA_C)
Type: Domain

This entry represents the C-terminal region of the alpha (large) chain of the class I ribonucleotide reductase (RNR). RNR's are responsible for the conversion of the ribose sugar of RNA into the deoxyribose sugar of DNA. This is the rate-limiting step of DNA biosynthesis. Class I RNR's generate the required radical (on tyrosine) via a "non-heme" iron cofactor which resides in the beta (small) subunit. The alpha subunit contains the catalytic and allosteric regulatory sites. The mechanism of this enzyme requires molecular oxygen . Escherichia coli contains two versions of this enzyme which are regulated independently (NrdAB and NrdEF, where NrdA and NrdE are the large chains ). Most organisms contain only one, but the application of the gene symbols NrdA and NrdE are somewhat arbitrary. Members of this group are found in diverse clades of bacteria, eukaryotes as well as numerous DNA viruses and phage.
Tetrahydromethanopterin S-methyltransferase, F subunit (MeTrfase_F_su)
Type: Domain

Many archaea have evolved energy-yielding pathways marked by one-carbon biochemistry featuring novel cofactors and enzymes. This domain is mostly found in MtrF, where it covers the entire length of the protein. This polypeptide is one of eight subunits of the N5-methyltetrahydromethanopterin: coenzyme M methyltransferase complex found in methanogenic archaea. This is a membrane-associated enzyme complex that uses methyl-transfer reactions to drive a sodium-ion pump . MtrF itself is involved in the transfer of the methyl group from N5-methyltetrahydromethanopterin to coenzyme M. Subsequently, methane is produced by two-electron reduction of the methyl moiety in methyl-coenzyme M by another enzyme, methyl-coenzyme M reductase.

In some organisms this domain is found at the C-terminal region of what appears to be a fusion of the MtrA and MtrF proteins . The function of these proteins is unknown, though it is likely that they are involved in C1 metabolism.
Type 3 secretion system chaperone YscG/PscG (T3SS_YscG_PscG)
Type: Family

YscG is a molecular chaperone for YscE, where both are part of the type III secretion system that in Yersinia is designated Ysc (Yersinia secretion). The secretion system delivers effector proteins, designated Yops (Yersinia outer proteins), in Yersinia . This entry family includes YscG from Yersinia, and similar type III secretion proteins in other species such as PscG in Pseudomonas aeruginosa, which is required for type III secretion needle assembly .
Type III secretion system effector YopR (T3SS_YopR)
Type: Family

Proteins in this entry are type III secretion system effectors, named differently in different species and designated YopR in Yersinia and AscH in Aeromonas salmonicida subsp. salmonicida . Yersinia employs a type III secretion system (T3SS) to secrete and translocate virulence factors into to the cytoplasm of mammalian host cells. One of the secreted virulence factors is YopR (Yersinia outer protein R, named Type 3 secretion system regulator YopR), encoded by the YscH (Yersinia secretion H) gene . This Yop protein is unusual in that it is released to the extracellular environment rather than injected directly into the target cell as are most Yop proteins . These are regulatory proteins that control the polymerisation of the needle .
Ribonucleotide reductase alpha chain (RNR_alpha)
Type: Family

Proteins in this entry represent a small clade of ribonucleoside-diphosphate reductase alpha chains which are sufficiently divergent from the usual Class I ribonucleotide reductase (RNR) alpha chains (NrdE or NrdA,

) to form a distinct group. The genes from Thermus thermophilus, Dichelobacter and Salinibacter are adjacent to the usual RNR beta chain.
Type III secretion system effector delivery regulator TyeA-related (T3SS_TyeA-rel)
Type: Domain

This entry represents a sequence region found in both small proteins of about 90 amino acids where it covers the whole sequence, and longer proteins of about 360 residues where it occurs in the C-terminal region. Some of the longer proteins (HrpJ) have N-terminal regions that contain

. These proteins belong to bacterial type III secretion systems, and include TyeA from the well-studied Yersinia systems. TyeA appears to be involved in calcium-responsive regulation of the delivery of type III effectors .
Iron hydrogenase, subset (Fe_hydrogenase_subset)
Type: Domain

This model describes iron-only hydrogenases of anaerobic and microaerophilic bacteria and protozoa. These proteins represent a subdivision within a larger family which includes proteins such as nuclear prelamin A recognition factor in animals. These proteins show some heterogeneity in terms of periplasmic, cytosolic or hydrogenosomic location, NAD or NADP dependence, and overall protein length.
Type III secretion system chaperone YscB (T3SS_YscB)
Type: Family

Members of this family include YscB of Yersinia and functionally equivalent (but differently named) proteins from type III secretion systems of other pathogens that affect animal cells. In Yersinia pestis, the secretion of effector proteins, termed Yersinia outer proteins (Yops), is regulated by the activity of the YopN/SycN/YscB/TyeA complex. YscB acts, along with SycN (

), as a chaperone for YopN, a key part of a complex that regulates type III secretion so that it responds to contact with the eukaryotic target cell .
Type III secretion system needle length determinant, C-terminal domain (T3SS_YscP_C)
Type: Domain

Proteins with this domain include YscP of the Yersinia type III secretion system and equivalent proteins in other pathogenic bacterial type III secretion systems. The entry describes the conserved C-terminal region. The N-terminal regions are poorly conserved, variable in length and often contain low-complexity sequences.
Type IV pilus secretin PilQ (Pilus_4_PilQ)
Type: Family

A number of proteins homologous to PilQ are involved in type IV pilus formation, competence for transformation, type III secretion, and type II secretion (also referred to as the main terminal branch of the general secretion pathway). Members of this family include PilQ itself, which is a component of the type IV pilus structure, from a number of species. In Haemophilus influenzae, the member of this family ComE is associated with the uptake of exogenous DNA, rather than with formation of a type IV pilus . HofQ from E. coli is also a member of this group involved in DNA uptake; in this case exogenous DNA is used as a nutrient source .
Type II secretion system protein GspD (T2SS_GspD)
Type: Family

General secretion pathway protein D (GspD) is the secretin component of the type II secretion system. GspD is closely homologous to the type IV pilus outer membrane secretin PilQ (

) and to the type III secretion system pore YscC/HrcC (

). The N-terminal part of GspD extends into the periplasm and may interact with secreted proteins as well as T2SS partner proteins .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Acetaldehyde dehydrogenase, acetylating (Acetaldehyde_DH_acetylating)
Type: Family

Aldehyde dehydrogenases (

and

) are enzymes which oxidize a wide variety of aliphatic and aromatic aldehydes using NAD(P) as a cofactor. In eukaryotes, at least twenty distinct aldehyde dehydrogenase families have been classified . Many aldehyde dehydrogenases have also been found in prokaryotic species. A glutamic acid and a cysteine residue have been implicated in the catalytic activity of mammalian aldehyde dehydrogenase, though these residues are not necessarily conserved in all the enzymes of this family.

The acetaldehyde dehydrogenase family (

) of bacterial enzymes catalyse the formation of acetyl-CoA from acetaldehyde in the degradation of phenols, cresols and catechol . Proteins in this entry occur in bacterial species and are annotated as probable acetaldehyde dehydrogenases, though this function has not been experimentally verified.
Pilus biogenesis, MshL (Pilus_biogenesis_MshL)
Type: Family

Proteins containing this region are predicted secretins, that is, outer membrane pore proteins associated with delivery of proteins from the periplasm to the outside of the cell. Related proteins include the GspD type II secretion family, the YscC/HrcC family type III secretion family, and the PilQ type IV pilus formation family. These proteins are found in gene clusters associated with MSHA (mannose-sensitive haemagglutinin) and related pili, and appear to be the secretin of this pilus system.
Pilus formation type IVB, outer membrane PilN (Pilus_4B_PilN)
Type: Family

Several related protein families encode outer membrane pore proteins for type II secretion, type III secretion, and type IV pilus formation. Proteins in this entry appear to be secretins for pilus formation, although they are quite different from PilQ. Members include the PilN lipoprotein of the plasmid R64 thin pilus, a type IV pilus. Some proteins may be examples of bundle-forming pilus B (bfpB).
Pilus biogenesis/stability type IV, PilW (Pilus_4_PilW)
Type: Family

Proteins in this entry are designated PilF and PilW . This outer membrane protein is required both for pilus stability and for pilus functions such as adherence to human cells. Members of this family contain copies of the TPR (tetratricopeptide repeat) domain.
Pilus biogenesis CpaD (Pilus_CpaD)
Type: Family

Proteins in this entry consist of a pilus biogenesis protein, CpaD, from Caulobacter, and homologues in other bacteria, including three in the root nodule bacterium Bradyrhizobium japonicum. The molecular function of the homologues is not known.
Pilus modification type IV, PilV (Pilus_4_PilV)
Type: Family

Pilus systems categorized as type IV pilins differ greatly from one another, with some showing greater similarity to type II or type III secretion systems than to each other. Members of this protein family represent the PilV protein of type IV pilus systems found in
Pseudomonas aeruginosa PAO1,
Pseudomonas syringae pv. tomato str. DC3000,
Neisseria meningitidis MC58,
Xylella fastidiosa 9a5c, and other species.
Dot/Icm secretion system ATPase DotB (Dot_Icm_DotB)
Type: Family

Proteins in this entry are the DotB component of Dot/Icm secretion systems, as found in the obligate intracellular pathogens Legionella pneumophila and Coxiella burnetii. While this system resembles type IV secretion systems and has been called a form of type IV, the literature now seems to favor calling this the Dot/Icm system. This family is most closely related to the TraJ proteins of plasmid transfer (

), rather than to proteins of other type IV secretion systems.
ATPase, plasmid transfer, TraJ (ATPase_plasmid-transfer_TraJ)
Type: Family

Proteins in this entry are predicted ATPases associated with plasmid transfer loci in bacteria. This family is most similar to the DotB ATPase (

) of a type-IV secretion-like system of the obligate intracellular pathogens Legionella pneumophila and Coxiella burnetii.
Dot/Icm secretion system IcmQ (Dot_Icm_IcmQ)
Type: Family

Proteins in this entry are the IcmQ component of Dot/Icm secretion systems, as found in the obligate intracellular pathogens Legionella pneumophila and Coxiella burnetii. While this system resembles type IV secretion systems and has been called a form of type IV, the literature now seems to favor calling this the Dot/Icm system. This protein was shown to be essential for translocation .
Ethanolamine utilisation EutJ (EutJ)
Type: Family

Salmonella typhimurium is capable of growth on ethanolamine as a sole source of carbon nitrogen and energy . During growth on this compound the cells form a multimolecular structure known as a metabolosome, which is similar to the carboxysome used by some photosynthetic bacteria to fix CO2, and is thought to contain the enzymes needed to metabolise this compound to acetyl-CoA. The metabolosome is not directly involved in the biochemistry of ethanolamine utilization -instead its role is thought to be to concentrate the enzymes involved in this process, while also protecting the cell from the build-up of toxic intermediates . The genes involved in growth on ethanolamine are encoded in a 17-gene operon known as the ethanolamine utilization (eut) operon. EutJ shows similarity to chaperonins and may play a role in assembly of the metabolosme , though it is not necessary for growth on this compound.
Flagellar, putative (Flagellar_put)
Type: Family

Proteins in this entry are encoded in a subset of bacterial flagellar operons, generally between genes designated flgD and flgE, in species as diverse as Bacillus halodurans and various other Firmicutes, Geobacter sulfurreducens, and Bdellovibrio bacteriovorus. The specific molecular function of this protein is unknown.
TrpR homologue YerC/YecD (YecD_YerC)
Type: Family

These proteins are found mostly in the Firmicutes (Bacillus and other related Gram-positive bacteria). They are similar in sequence to the trp operon repressor TrpR

, but represent a distinct clade. At least one species, Xylella fastidiosa, in the Proteobacteria, has a member of both this family and

. Several genomes with a member of this family do not synthesize tryptophan, and members of this family should not be considered trp operon repressors without new evidence.
Type II secretion system protein GspE (T2SS_GspE)
Type: Family

GspE is a cytoplasmic hexameric ATPase of the type II secretion system. It contains three domains (N1E, N2E and CTE) of which the N1E domain is associated with the cytoplasmic domain of the inner membrane protein GspL .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Muconate/chloromuconate cycloisomerase (Chloromuconate_cycloisomerase)
Type: Family

This family consists of muconate cycloisomerase (or Muconate Lactonizing Enzyme (MLE);

) and chloromuconate cycloisomerase (or chloromuconate lactonizing enzymes (Cl-MLEs);

), enzymes that often overlap in specificity. It does not include more distantly related proteins such as mandelate racemase (

).

MLE, a homooctameric enzyme, catalyses the conversion of cis,cis-muconate to muconolactone in the catechol branch of the beta-ketoadipate pathway . This pathway is used in soil microbes to breakdown lignin-derived aromatics, catechol and protocatechuate, to citric acid cycle intermediates. Some bacterial species are also capable of dehalogenating chloroaromatic compounds by the action of Cl-MLEs. MLEs are members of the enolase superfamily characterised by the presence of an enolate anion intermediate which is generated by abstraction of the alpha-proton of the carboxylate substrate by an active site residue and that is stabilised by coordination to the essential Mg2+ ion .