SII-SWORD/CoKE huggingface dataset:
Glutamate synthase large subunit-like protein (GltB)
Type: Family

Glutamate synthase (GOGAT, GltS) is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate (2-OG) and L-glutamine via intramolecular channeling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation . GOGAT is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor .

There are four classes of glutamate synthase (GOGAT) , :

Bacterial NADPH-dependent GOGAT (NADPH-GOGAT,

). This standard bacterial NADPH-GOGAT (GltS) is composed of a large (alpha, GltB) subunit, and a small (beta, GltD) subunit.

Ferredoxin-dependent GOGAT in cyanobacteria and plants (Fd-GOGAT from photosynthetic cells,

) displays a single-subunit structure corresponding to the large bacterial subunit.

Pyridine-linked GOGAT in both photosynthetic and nonphotosynthetic eukaryotes (eukaryotic GOGAT or NADH-GOGAT,

) displays a single-subunit structure corresponding to the fusion of the small and the large bacterial subunits.

The archaeal type with stand-alone proteins corresponding to the N-terminal, FMN-binding, and the C-terminal domains of the large subunit and to the small subunit.

The large (alpha, GltB) subunit of bacterial glutamate synthase (GOGAT) consists of three domains: the N-terminal amidotransferase domain (

), the central domain, and the C-terminal domain (

). This entry represents a stand-alone version of the central domain. The stand-alone form occurs in the archaeal-type of GOGAT, where the large subunit is represented by three separate proteins, corresponding to the three domains of the "standard" bacterial enzyme .

The second (central) domain of the bacterial GOGAT large subunit consists of a

linker domain and the FMN-binding domain (

). The FMN-binding domain has a β/α barrel topology. In this domain, the 2-iminoglutarate intermediate, formed upon the addition of ammonia onto 2-oxoglutarate, is reduced by the FMN cofactor producing the second molecule of L-glutamate . This domain also contains the enzyme 3Fe-4S cluster .All members of this entry contain the FMN-binding domain. However, they lack the

linker domain, and some have 1-3 copies of

(4Fe-4S binding domain) in the N-terminal region.

Originally, only the ORF encoding the central domain of GOGAT was recognised and annotated as GltB in archaea, and the rest of the large subunit was thought to be missing, which may lead to some misannotations . This led to speculations that the archaeal form of the GOGAT large subunit is the ancestral minimum form of the enzyme. Later analysis showed, however, that in all archaea where the large subunit has been found, its entire sequence is represented by three separate ORFs .
ANTAR transcription anti-termination regulator (ANTAR_transcrpt_antiterm_reg)
Type: Family

This group represents the stand-alone version of an RNA-binding ANTAR domain (AmiR-like) that affects anti-termination . This domain is most often found fused to the CheY-like receiver domain to form response regulator anti-terminator (

). Superficially, the coiled-coil and three-helix bundle that form this domain in AmiR (

) appear radically different from the compact HTH DNA-binding domain of the NarL protein. However, the last three helices in AmiR are very similar in length and hydropathy profiles to those of NarL and its homologues, and are arranged in a very similar topology, suggesting an evolutionary relationship . These C-terminal helices of AmiR appear to be essential for its transcription anti-termination activity . However, helix-turn-helix domains like those in NarL or OmpR are adapted to sequence-specific binding in the major groove of double-stranded B-form DNA. It is not clear how such a structure might function in a protein whose role is to prevent the formation of a termination stem-loop structure, by binding single-stranded RNA .
Methenyltetrahydromethanopterin dehydrogenase, Hmd-type (METHMP_Hmd)
Type: Family

The N(5),N(10)-methylenetetrahydromethanopterin dehydrogenase system of methanogenic archaea is composed of H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd,

, this group) and F420-dependent methylenetetrahydromethanopterin dehydrogenase (

). Hmd is an iron-sulphur-cluster-free enzyme that contains an intrinsic CO ligand bound to iron .

contains two distinct subgroups: one has been experimentally characterised as H2-forming N(5),N(10)-methenyltetrahydromethanopterin dehydrogenase (Hmd or HmdI,

), and the other one contains isozymes that have not been experimentally characterised (HmdII and HmdIII,

). Because all three isozyme forms are present in each of the corresponding sequenced genomes, it has been suggested that HmdII and HmdIII may not exhibit Hmd activity and may have a different biological function .

For additional information please see .
Peptidase M61 (Peptidase_M61)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to the MEROPS peptidase family M61 (glycyl aminopeptidase family, clan MA(E)).The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH. The type example is glycyl aminopeptidase from Sphingomonas capsulata.
Fosfomycin resistance kinase, FomA-type (Fosfomycin_R_FomA-type)
Type: Family

This entry represents a group of isopentenyl phosphate kinases (IPKs) from archaea and plants. They catalyze the formation of isopentenyl diphosphate (IPP), the building block of all isoprenoids . This entry also includes FomA protein from Streptomyces. IPKs and FomA are architecturally very similar .

Fosfomycin (L-(cis)-1,2-epoxy propyl phosphonic acid) is an antibiotic produced by some species of Streptomyces and Pseudomonas. As an analogue of phosphoenolpyruvate (PEP), this compound irreversibly inhibits PEP UDP-N-acetylglucosamine-3-O-enolpyruvyltransferase (enolpyruvyltransferase), which catalyses the first step of peptidoglycan biosynthesis . FomA is one of the fosfomycin resistance kinases. Together with FomB (encoded in the fosfomycin biosynthetic gene cluster of Streptomyces wedmorensis), FomA confer fosfomycin resistance on Escherichia coli . FomA catalyses phosphorylation of fosfomycin to fosfomycin monophosphate, and FomB phosphorylation of fosfomycin monophosphate to fosfomycin diphosphate, in the presence of ATP and a magnesium ion . Surprisingly, while FomA homologues are present in many organisms, including fosfomycin-producing ones, no homologues of FomB are detected to date.

FomA and related sequences are members of the Amino Acid Kinase Superfamily (AAK).
Ku80 (Ku80)
Type: Family

This group consists of eukaryotic proteins containing the Ku80 domain. In eukaryotes it has been shown that Ku protein is involved in repairing DNA double-strand breaks by non-homologous end-joining . Ku is a heterodimer of approximately 70kDa and 80kDa subunits . Both these subunits have strong sequence similarity and it has been suggested that they may have evolved by gene duplication from a homodimeric ancestor in eukaryotes . The prokaryotic Ku members are homodimers and they have been predicted to be involved in the DNA repair system, which is mechanistically similar to the eukaryotic non-homologous end joining . Recent findings have implicated yeast Ku in telomeric structure maintenance in addition to non-homologous end-joining . Some of the phenotypes of Ku-knockout mice may indicate a similar role for Ku at mammalian telomeres .

Evolutionary notes: With the currently available phyletic information it is difficult to determine the correct evolutionary trajectory of the Ku domain. It is possible that the core Ku domain was present in bacteria and archaea even before the presence of the eukaryotes. Eukaryotes might have vertically inherited the Ku-core protein from a common ancestor shared with a certain archaeal lineage or through horizontal transfer from bacteria. Alternatively, the core Ku domain could have evolved in the eukaryotic lineage and then horizontally transferred to the prokaryotes. Sequencing of additional archaeal genomes and those of early-branching eukaryotes may help resolve the evolutionary history of the Ku domain.

Structure notes: The eukaryotic Ku heterodimer is comprised of an α/β N-terminal domain, a central β-barrel domain and a helical C-terminal arm . Structural analysis of the Ku70/80 heterodimer bound to DNA indicates that subunit contacts lead to the formation of a highly charged channel through which the DNA passes without making any contacts with the DNA bases .

For additional information please see .
Alginate O-acetyltransferase AlgI/D-alanyl transfer protein DltB (Ac/AlaTfrase_AlgI/DltB)
Type: Family

The biochemically characterised members of this group are enzymes that transfer organic acids, typically fatty acids, onto hydroxyl groups of membrane-embedded targets. They contain a characteristic domain for O-acyl transferases,

, in which a conserved histidine has been suggested to be the active site residue . These enzymes are multispan membrane proteins involved in the modification of bacterial surface and extracellular polyliposaccharides that play a variety of roles in bacterial survival. Based on sequence similarity this family has been classified into two subgroups:

1. DltB (

): DltB orthologues are present in Gram-positive bacteria. The dlt operon is responsible for D-alanine esterification of both lipoteichoic acid and wall teichoic acid. The dlt operon contains five genes, dltA-dltE; dltB codes for the enzyme that transfers D-alanine to the wall lipotechtoic acids .

2. AlgI (

): AlgI homologues are present mainly in Gram-negative bacteria, though there are a few members from Gram-positive bacteria. The
algI
gene is often linked to genes for type II membrane proteins that have the conserved amino acid motifs: P[x]K and RTD[x]HW. In Gram-negative bacteria, AlgI is involved in the synthesis of alginate (linear polymer of alpha L-gulunorate and beta-D-mannuronate linked by beta1-4 glycosidic bonds) . AlgI paralogues in Pseudomonas syringae and Pseudomonas fluorescens are involved in the O-acetylation of cellulose . In the Gram-positive strain Clostridium acetobutylicum, an
algI
homologue is also adjacent to the cellulose biosynthetic genes.
NUDIX hydrolase, YfcD, predicted (NUDIX_hydrolase_YfcD_pred)
Type: Family

This entry represents a family of uncharacterised proteins that contain a NUDIX hydrolase domain (

).
[NiFe]-hydrogenase-3-type complex Eha, EhaR (NiFe_hyd_3_EhaR)
Type: Family

[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster .

Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family . Members of this subgroup include:

Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coli

CO-induced hydrogenase (Coo) from Rhodospirillum rubrum

Mbh hydrogenase from Pyrococcus furiosus

Eha and Ehb hydrogenases from Methanothermobacter species

Ech hydrogenase from Methanosarcina barkeri

Energy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe] hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe] hydrogenases function as ion pumps.

Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S] polyferredoxin, ten other predicted integral membrane proteins (EhaA

, EhaB

, EhaC

, EhaD

, EhaE

, EhaF

, EhaG

, EhaI

, EhaK

, EhaL

and

) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) . The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.

This entry represents proteins that are predicted to be the hydrophilic EhaR subunits of Eha-type energy-converting [NiFe] hydrogenase complexes.
Trehalose phosphatase-like (TPP-like)
Type: Family

This entry represents a family of bacterial proteins that includes Trehalose phosphatase from Pseudomonas aeruginosa (TPP). This enzyme hydrolyses the metabolite trehalose 6-phosphate (T6P), whose accumulation may result in a lethal phenotype. The protein adopts the overall fold of the HAD superfamily (

) with a Rossmann fold and an α/β cap domain .
Uncharacterised conserved protein, UCP033642 (UCP033642)
Type: Family

There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.
Uncharacterised conserved protein, DsbB-like (Uncharacterised_DsbB)
Type: Family

This entry represents a family of conserved hypothetical proteins with DsbB domain.
Chondroitin sulfate ABC endolyase (Chondroitinase_ABC_I)
Type: Family

Chondroitin sulfate ABC endolyase is a broad-specificity glycosaminoglycan lyase, which degrades the polysaccharides chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate and to a lesser extent hyaluronan . It is able to promote functional recovery in the injured central nervous system (CNS), via its role in the disruption of the normal organisation of the extracellular matrix .
Calcineurin-like phosphoesterase (Calcineurin-like_Pesterase)
Type: Family

These conserved animal proteins contain one copy of the calcineurin-like phosphoesterase domain (

) and possess motifs characteristic of a variety of enzymatically active phosphoesterases , including acid and alkaline phosphatases, phosphoprotein phosphatases, 5'-nucleotidase, bis(5'-nucleosyl)-tetraphosphatase (symmetrical), sphingomyelin phosphodiesterase, 2',3'-cylic-nucleotide 2'-phosphodiesterase, and 3',5'-nucleotide phosphodiesterase CpdA. Two human genes have been identified. One, expressed in fetal brain, was isolated from the chromosome 11p13 region associated with mental retardation component of the WAGR (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) syndrome. The other, expressed in adult tissues, was mapped to chromosome 22 .
5-deoxy-glucuronate isomerase, IolB (Deoxy-glucuronate_isom_IolB)
Type: Family

Members of this family include several bacterial myo-inositol catabolism (IolB) proteins. The Bacillus subtilis inositol operon (iolABCDEFGHIJ) is involved in myo-inositol catabolism. Glucose repression of the iol operon induced by inositol is exerted through catabolite repression mediated by CcpA and the iol induction system mediated by IolR . IolB catalyses the isomerisation of 5-deoxy-D-glucuronic acid to produce 2-deoxy-5-keto-D-gluconic acid .
Cytochrome P450, cholesterol 7-alpha-monooxygenase-type (Cyt_P450_CYP7A1-type)
Type: Family

This group represents cytochrome P450, CYP7A1 type. Gene cyp7a1 codes for the enzyme cholesterol 7-alpha-monooxygenase, which catalyses a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. This enzyme is important for cholesterol homeostasis . Some of the enzymes belonging to this group are 7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase, also involved in bile acid biosynthesis, and prostacyclin synthase, which catalyses the isomerization of prostaglandin H2 to prostacyclin (prostaglandin I2).
Mst1/2 SARAH domain (Mst1_2_SARAH_domain)
Type: Domain

This entry represents the C-terminal SARAH domain of Serine/threonine-protein kinase 4 (STK4) (also known as Mst1) and STK4 (also known as Mst2). The Mst1 SARAH domain interacts with Rassf1 and Rassf5 by forming a heterodimer which mediates the apoptosis process .

The SARAH (Sav/Rassf/Hpo) domain is found at the C terminus in three classes of eukaryotic tumour suppressors that give the domain its name. In the Sav (Salvador) and Hpo (Hippo) families, the SARAH domain mediates signal transduction from Hpo via the Sav scaffolding protein to the downstream component Wts (Warts); the phosphorylation of Wts by Hpo triggers cell cycle arrest and apoptosis by down-regulating cyclin E, Diap 1 and other targets . The SARAH domain is also involved in dimerisation, as in the human Hpo orthologue, Mst1, which homodimerises via its C-terminal SARAH domain. The SARAH domain is found associated with other domains, such as protein kinase domains, WW/rsp5/WWP domain (

), C1 domain (

), LIM domain (

), or the Ras-associating (RA) domain (

).
Gurmarin/antimicrobial peptide (Gurmarin/antimicrobial_peptd)
Type: Family

This peptide has six cysteines involved in three disulphide bonds.
The presence of a 'disulphide through disulphide knot' structurally defines this protein as a knottin: the peptide contains a global fold which involves a cysteine-knotted three-stranded antiparallel β-sheet along with a flexible loop and four beta-reverse turns. It also has an amphiphilic character which is the main structural basis of its biological function . The peptides in this entry belong to the AMP family.
Protein CotJB, domain (CotJB_dom)
Type: Domain

The cotJ operon proteins affect spore coat composition, and is controlled by sigma E. The genes, which include CotJB, are either required for the normal formation of the inner layers of the coat or are themselves structural components of the coat . CotJB has been identified as a spore coat protein .
Protein of unknown function DUF3842 (DUF3842)
Type: Family

This family of proteins has no known function.
Spore surface protein CDIF630_02480 (CDIF630_02480-like)
Type: Family

This family of proteins, previously known as DUF3787, represents the spore surface protein CDIF630_02480 from Clostridioides difficile and related proteins found in Clostridia. CDIF630_02480 contribute to maintain proper thickness of the spore coat and exosporium layers . Members of this family contain a conserved TAAW sequence motif that may be functionally important.
Protein of unknown function DUF3785 (DUF3785)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are approximately 140 amino acids in length and share two CXXC motifs suggesting these are zinc binding proteins. In clostridia proteins are found in an operon with three signalling proteins, suggesting that they are involved in DNA-binding transcription regulator downstream of an as yet unknown signalling pathway.
Protein of unknown function DUF3841 (DUF3841)
Type: Family

This family of proteins has no known function.
Domain of unknown function DUF3837 (DUF3837)
Type: Domain

This entry represents a small, compact all-α helical domain of unknown function. This domain is currently only found in Clostridiales species.
Protein of unknown function DUF3822 (DUF3822)
Type: Family

This is a family of uncharacterised bacterial proteins. However, structural-similarity searches indicate the family takes on an actin-like ATPase fold.
Protein of unknown function DUF3843 (DUF3843)
Type: Family

A family of uncharacterised proteins found by clustering human gut metagenomic sequences .
Protein of unknown function DUF3847 (DUF3847)
Type: Family

This entry represents a family of uncharacterised proteins that were found by clustering human gut metagenomic sequences .
Protein of unknown function DUF3851 (DUF3851)
Type: Family

This entry represents a family of uncharacterised proteins that were found by clustering human gut metagenomic sequences .
Protein of unknown function DUF3813 (DUF3813)
Type: Family

This entry represents a family of proteins mainly found in Bacillus, including Uncharacterized protein YizC from Bacillus subtilis (strain 168). YizC might be involved in sporulation .
Protein of unknown function DUF3867 (DUF3867)
Type: Family

This entry represents a family of functionally uncharacterised proteins that are found in bacteria. Proteins in this family are approximately 190 amino acids in length.
Protein of unknown function DUF3809 (DUF3809)
Type: Family

This group of proteins is found in the Deinococci bacteria. It is functionally uncharacterised.
Protein of unknown function DUF3780 (DUF3780)
Type: Family

This family of proteins have no known function. There are two conserved sequence motifs: PEERWWL and GWR. This family is found in a very sporadic set of bacterial species, suggesting that it may have been horizontally transferred. One protein (

) is annotated as occurring on a plasmid.
Beta-lactamase-inhibitor protein BLIP domain superfamily (BLIP_dom_sf)
Type: Homologous_superfamily

The beta-lactamase-inhibitor protein (BLIP) is produced by Streptomyces species. BLIP acts as a potent inhibitor of beta-lactamases such as TEM-1, which is the most widespread resistance enzyme to penicillin antibiotics. BLIP binds competitively to TEM-1 and makes direct contacts with TEM-1 active site residues. BLIP is able to inhibit a variety of class A beta-lactamases, possibly through flexibility of its two domains. The two tandemly repeated domains of BLIP have an α(2)-β(4) structure, the β-hairpin loop from domain 1 inserting into the active site of beta-lactamase . BLIP shows no sequence similarity with BLIP-II, even though both bind to and inhibit TEM-1 .

This superfamily represents the structural domains of BLIP .