SII-SWORD/CoKE huggingface dataset:
DNA polymerase V/Myb-binding protein 1A (DNA_pol_V/MYBBP1A)
Type: Family

Proteins of this family are predominantly nucleolar. Myb-binding protein 1A (MYBBP1A) is a transcription regulator that may play an important role in the cellular stress response . This family also includes the fifth essential DNA polymerase (Pol5p) of Schizosaccharomyces pombe (Fission yeast) and Saccharomyces cerevisiae (Baker's yeast) (

). Pol5p is localized exclusively to the nucleolus and binds near or at the enhancer region of rRNA-encoding DNA repeating units . This protein was originally thought to be a DNA polymerase, however, later reseach indicated its involvement in ribosome assembly .
O-antigen ligase-related domain (O-antigen_ligase-rel_domated)
Type: Domain

This entry represents a domain found in a group of bacterial proteins that is involved in the synthesis of O-antigen, a lipopolysaccharide found in the outer membrane in Gram-negative bacteria. This family includes O-antigen ligases such as E. coli RfaL (also known as WaaL) . This entry also includes PilO (

), which is an oligosaccharyltransferases involved in O-linked protein glycosylation .
Mediator complex, subunit Med6 (Mediator_Med6)
Type: Family

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.

Regulation of mRNA synthesis requires intermediary proteins that transduce regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Three types of intermediary factors that enable the basal transcription machinery to respond to transcriptional activator proteins bound to regulatory DNA sequences have been identified: (i) TAFIIs, which associate with TATA-binding protein (TBP) to form TFIID; (ii) mediator, which associates with RNA polymerase II to form a holo-polymerase; and (iii) coactivators such as human upstream stimulatory activity (USA), mammalian CBP/P300, yeast ADA complex, and HMG proteins. The interaction of these multiprotein complexes with activators and general transcription factors is essential for transcriptional regulation.

This family of proteins represent the transcriptional mediator protein subunit 6 that is required for activation of many RNA polymerase II promoters and which are conserved from yeast to humans .
Surfeit locus 6 (SURF6)
Type: Family

This entry represents the surfeit locus protein SURF6 from mammals and its homologues from plants and fungi.

In mammals, SURF6 is a component of the nucleolar matrix and has a strong binding capacity for nucleic acids . SURF6 is always found in the nucleolus regardless of the phase of the cell cycle suggesting that it is a structural protein constitutively present in nucleolar substructures. A role in rRNA processing has been proposed for this protein.
Protein of unknown function DUF658 (DUF658)
Type: Family

These are proteins of unknown function found in Lactococcus lactis and in their associated bacteriophage.
Domain of unknown function DUF659 (DUF659)
Type: Domain

These are transposase-like proteins with no known function.
Ribosomal biogenesis regulatory protein (Ribosom_reg)
Type: Family

This is a family of eukaryotic ribosomal biogenesis regulatory (Rrs1) proteins. Rrs1 was isolated as a factor related to a secretory defect that caused the transcriptional repression of both rRNA and ribosomal protein genes . This protein is known to localize in the nucleolus where it acts as a ribosome assembly factor. It also localizes at the nuclear periphery where it directly interacts with the membrane-spanning SUN domain protein Mps3 and silent information factor Sir4, both involved in telomere clustering and silencing .

The N-terminal region of Rrs1 plays a role in ribosome biogenesis via interaction with the N-terminal Brix domain of Rpf2. The topology of the Brix domain presents an incomplete duplication of the anticodon-binding domain (ABD) of class IIa aminoacyl-tRNA synthetases. The structure of the Rpf2-Rrs1 complex shows that the N-terminal region of Rrs1 completes the Brix domain of Rpf2 and creates a double anticodon-binding domain .
BLUF domain (BLUF_domain)
Type: Domain

The BLUF domain (named for sensors of Blue-Light Using FAD) is an FAD-binding protein domain. BLUF domains are present in various proteins, primarily from bacteria. For example a BLUF domain is found at the N terminus of the AppA protein from Rhodobacter sphaeroides . BLUF domains are involved in sensing blue-light (and possibly redox) using FAD, and are similar to the flavin-binding PAS domains and cryptochromes. Their predicted secondary structure reveals that the BLUF domains have a novel FAD-binding fold .
Late expression factor 8 (LEF-8) (LEF-8)
Type: Family

Late expression factor 8 (LEF-8) is one of the primary components of RNA polymerase produced by polyhedrosis viruses. LEF-8 shows homology to the second largest subunit of prokaryotic DNA-directed RNA polymerase .
CC domain (CC_domain)
Type: Domain

This short domain contains four conserved cysteines that are probably required for the formation of two disulphide bonds. The domain is found in Chtb-1 from Caenorhabditis elegans and similar nematode proteins. The domain is named after the characteristic CC motif.

Chitin binding domain (ChtBD2) containing chtb-1 (chtb-1) is predicted to enable chitin binding activity. It is also predicted to be located in the extracellular region.
Poxvirus F11 (Poxvirus_F11)
Type: Family

This entry represents the poxvirus Protein F11 from Vaccinia virus, also known as Protein OPG055, and similar sequences from poxvirus. They are early virus proteins. F11 stimulates increases in peripheral microtubule dynamics and may increase the motility of the infected cells, contributing to cell-to-cell spread of the virus. It seems to inhibit the signalling via the GTPase RHOA and DIAPH1/mDia .
YHS domain (YHS_dom)
Type: Domain

This short presumed domain is about 50 amino acid residues long. It often contains two cysteines that may be functionally important. This domain is found in cation transporting ATPases, some oxygenase components of multicomponent enzymatic monooxigenases, and in a set of uncharacterised membrane proteins including

. This domain is named after three of the most conserved amino acids it contains. The domain may be metal binding. This domain is duplicated in some copper transporting ATPases.
Poxvirus VLTF3, late transcription factor (Poxvirus_VLTF3)
Type: Family

Members of this family are approximately 26kDa, and are involved in trans-activation of late transcription .
Poxvirus A51 (Poxvirus_A51)
Type: Family

This entry represents Vaccinia virus A51, also known as Protein OPG181, and its homologues from poxvirus. This protein associates with ubiquitin and stabilises host microtubules, promotes viral protein stability, and plays an essential role in viral replication in vertebrate cells .
RAB6-interacting golgin (GORAB)
Type: Family

This entry represents RAB6-interacting golgin, including SCYL1BP1 (also known as GORAB) from humans. SCYL1BP1 localises to the Golgi apparatus and interacts with Rab6 . Therefore, SCYL1BP1 is identified as a golgin, a protein that tether vesicles to the Golgi apparatus.
Ribosome biogenesis protein BMS1/TSR1, C-terminal (BMS1_TSR1_C)
Type: Domain

This domain is found at the C terminus of the ribosome biogenesis protein BMS1 and TSR1 families, which may act as a molecular switch during maturation of the 40S ribosomal subunit in the nucleolus.
Peptidase M55, D-aminopeptidase (Peptidase_M55)
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 MEROPS peptidase family M55 (DppA aminopeptidase family, clan MN). The type example is Bacillus subtilis DppA, which is a binuclear zinc-dependent D-specific aminopeptidase. The structure reveals that DppA is an example of a self-compartmentalising protease, of which the proteasome is the most extensively studied. The DppA enzyme is composed of identical 30kDa subunits organised in a decamer with 52 point-group symmetry. A 20 A wide channel runs through the complex, giving access to a central chamber holding the active sites. DppA and its homologues are characterised by the presence of the SXDXEG motif . The only known substrates are D-Ala-D-Ala and D-Ala-Gly-Gly.
AstE/AspA barrel-sandwich hybrid domain (Aste_AspA_hybrid_dom)
Type: Domain

This entry represents the barrel-sandwich hybrid domain found in Succinylglutamate desuccinylase (AstE), aspartoacylase (AspA) and related enzymes. AstE catalyses the fifth and last step in arginine catabolism by the arginine succinyltransferase pathway whereas AspA cleaves acylaspartate into a fatty acid and aspartate. Mutations in human AspA lead to Canavan disease disease . The domain represented by this entry has similarity to known barrel-sandwich domains that are defined by sandwich of half-barrel shaped β-sheets. This domain is also described as shielding domain as it was found to cover the enzyme active site and thus limiting its accessibility .
SIP-like, Rossmann fold domain (SIP_rossman_dom)
Type: Domain

This entry represents the domain found C-terminal in SIPs, mostly found in gram-negative bacteria such as

which could belong to SIP subgroup I. This domain has a three-layer αβα architecture with a Rossmann fold topology . This entry also includes Mycobactin import ATP-binding/permease protein IrtA, where this domain is found in the N-terminal region in between

and

.

Siderophore-interacting proteins (SIPs) are flavin-dependent enzymes that catalyse the release of iron from the siderophore complex by facilitating the reduction of Fe(III) to Fe(II). Structural and kinetic studies of these enzymes have identified two different families: the ferric siderophore reductases (FSRs) and the SIPs. FSRs contain an iron-sulphur cluster, which is absent in SIPs. SIPs can be further classified into two subgroups, which differ in cofactor preference. Subgroup I is characterised by having a longer α-helical C-terminal and preferring NADH, while subgroup II SIPs have an extended N-terminal and utilise NADPH .

Mycobactin import ATP-binding/permease protein IrtA is part of the IrtAB complex, an ATP-binding cassette (ABC) transporter that plays a crucial role in iron acquisition in Mycobacterium tuberculosis. IrtAB is responsible for importing iron-loaded siderophores called mycobactins and carboxymycobactins into the bacterial cell .
Hydrogenase/Urease accessory protein HupE/UreJ protein (HupE_UreJ)
Type: Family

This family of proteins are hydrogenase/urease accessory proteins. R. leguminosarum HupE is a transmembrane nickel permease that may be required for hydrogen uptake . UreJ is a transmembrane protein shareing homology with HupE. Its function is not clear .
Conjugal transfer TrbC/type IV secretion VirB2 (TrbC/VirB2)
Type: Family

Conjugal transfer protein, TrbC has been identified as a subunit of the pilus precursor in bacteria. The protein undergoes three processing steps before gaining its mature cyclic structure. This family also contains several VirB2 type IV secretion proteins. The virB2 gene encodes a putative type IV secretion system and is known to be a pathogenicity factor in Bartonella species .
Ribosome modulation factor (Ribosome_modulation_factor)
Type: Family

This entry contains ribosome modulation factors (RMF). They associate with 70s ribosomes and converts them to a dimeric form (100S ribosomes) which appear during the transition from the exponential growth phase to the stationary phase of Escherichia coli cells .

It has been proposed that RMF mediates the formation of a 'storage ribosome', the 100S particle, in stationary phase by inactivating excess ribosomes to protect them from degradation and to maintain the required balance between the concentrations of ribosomes and protein synthesis factors in order to maintain translational elongation efficiency .

This entry also contains some phage proteins.
Arginine N-succinyltransferase AstA/AruG (Arg_succinylTrfase_AstA/AruG)
Type: Family

Arginine N-succinyltransferase catalyses the transfer of succinyl-CoA to arginine to produce succinylarginine. This is the first step in arginine catabolism via the arginine succinyltransferase pathway. Six major L-arginine-degrading pathways have been described for prokaryotes . Arginine succinyltransferase AstA (

) is the first enzyme of the succinyltransferase (AST) pathway operon consists of five genes . In a few species, such as Pseudomonas aeruginosa, arginine succinyltransferase consist of a heterodimer of subunits alpha (AstA) and beta (AruG) .
SERRATE/Ars2 , C-terminal (SERRATE/Ars2_C)
Type: Domain

This domain can be found in the C terminus of the SERRATE (SE) from plants and its homologue, Ars2, from animals. They play a role in nuclear RNA metabolism. They interact with the nuclear cap-binding complex (CBC) and mediates interactions with diverse RNA processing and transport machineries in a transcript-dependent manner. Interestingly, the plant SERRATE does not have the RNA recognition motif (RRM) domain found in metazoans and S. pombe .
Cyclodeaminase/cyclohydrolase (Cyclodeamin/CycHdrlase)
Type: Domain

Enzymes containing the cyclodeaminase domain function in channelling one-carbon units to the folate pool. In most cases, this domain catalyses the cyclisation of formimidoyltetrahydrofolate to methenyltetrahydrofolate as shown in reaction (1). In the methylotrophic bacterium Methylobacterium extorquens, however, it catalyses the interconversion of formyltetrahydrofolate and methylenetetrahydrofolate ,as shown in reaction (2)

(1) 5-formimidoyltetrahydrofolate = 5,10-methenyltetrahydrofolate + NH(3)

(2) 10- formyltetrahydrofolate = 5,10-methenyltetrahydrofolate + H(2)O

In prokaryotes, this domain mostly occurs on its own, while in eukaryotes it is fused to a glutamate formiminotransferase domain (which catalyses the previous step in the pathway) to form the bifunctional enzyme formiminotransferase-cyclodeaminase . The eukaryotic enzyme is a circular tetramer of homodimers , while the prokaryotic enzyme is a dimer .

The crystal structure of the cyclodeaminase enzyme (

) from Thermaotoga maritima has been studied . It is a homodimer, where each monomer is composed of six α helices arranged in an up and down helical bundle, forming a novel fold. The location of the active site is not known, but sequence alignments revealed two clusters of conserved residues located in a deep pocket within the dimmer interface. This pocket was large enough to accommodate the reaction product and it was postulated that this is the active site.
5-keto 4-deoxyuronate isomerase (KduI)
Type: Family

This family of bacterial proteins have been characterised as 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase. It is coded for by kdul and is involved in the fourth step in pectin degradation.

4-deoxy-L-threo-5-hexosulose uronate = 3-deoxy-D-glycero-2,5-hexodiulosonate

Although this enzyme is found in Escherichia coli, its role is uncertain since E. coli is not known to degrade the polysaccharides which are potential sources of 5-keto-4-deoxyuronate .
RNA polymerase sigma factor 54, core-binding domain (RNA_pol_sigma_54_core-bd)
Type: Domain

Bacterial core RNA polymerases (with subunit composition alpha2-β-β') must combine with a sigma subunit to transcribe from specific DNA promoter sequences. This domain, the core-binding domain of sigma factor 54, is a four-helical domain with negative charge that binds and makes a direct interaction with the core RNA polymerase to form an enhancer dependent holoenzyme and triggers the initiation of transcription .
Flp/Fap pilin component (Flp_Fap)
Type: Family

This entry is for the fimbriae associated protein Flp/Fap pilin component.
IraD/Gp25-like (IraD/Gp25-like)
Type: Domain

This domain is found in baseplate protein Gp25 from phage T4 and related phages, and Gp25-like proteins from bacteria . Gp25 is a component of the conserved wedge in the inner part of the baseplate and serves as a nucleus for sheath polymerisation, playing a critical role in sheath assembly and contraction . The EPR motif (Glu-Pro-Arg, residues 85-87 of gp25) is conserved across all members of the family including orthologs from the RpoS-mediated general stress response system (called IraD) . This motif interacts with the 'core bundle' composed of orthologs of T4 gp6 and gp7 proteins in contractile injection systems.
Carbohydrate-selective porin OprB (Carb-sel_porin_OprB)
Type: Family

The carbohydrate-selective porin OprB family includes the Pseudomonas aeruginosa porin B, a substrate-selective channel for a variety of different sugars. This protein may facilitate diffusion of a variety of diverse compounds, but is probably restricted to carbohydrates, and does facilitate glucose fusion across the outer membrane.
Bacterioopsin activator-type, HTH domain (HTH_bacterioopsin)
Type: Domain

Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. This entry represents the HTH DNA binding domain found in bacterioopsin transcriptional activator from Halobacterium salinarium (Halobacterium halobium) and other proteins, mainly from Halobacteria.
CHORD domain (CHORD_dom)
Type: Domain

Cysteine- and histidine-rich domains (CHORDs) are 60-amino acid modules that bind two zinc ions. They are usually arranged in tandem and are found in all tested eukaryotes, with the exception of yeast, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. Six cysteine and two histidine residues are invariant within the CHORD domain. Three other residues are also invariant and some positions are confined to positive, negative, or aromatic amino acids .
CS domain (CS_dom)
Type: Domain

The bipartite CS domain, which was named after CHORD-containing proteins and SGT1 , is a ~100-residue protein-protein interaction module. The CS domain can be found in stand-alone form, as well as fused with other domains, such as CHORD (

), SGS (

), TPR (

), cytochrome b5 (

) or b5 reductase, in multidomain proteins .

The CS domain has a compact antiparallel β-sandwich fold consisting of seven β-strands .

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

Eukaryotic proteins of the SGT1 family.

Eukaryotic Rar1, related to pathogenic resistance in plants, and to development in animals.

Eukaryotic nuclear movement protein nudC.

Eukaryotic proteins of the p23/wos2 family, which act as co-chaperone.

Animal b5+b5R flavo-hemo cytochrome NAD(P)H oxydoreductase type B.

Mammalian integrin beta-1-binding protein 2 (melusin).
LRAT domain (LRAT_dom)
Type: Domain

This domain (LRAT domain) is found in a variety of proteins, including lecithin retinol acyltransferase (LRAT), HRAS-like suppressors (HRASLS1-5) and proteins FAM84A and FAM84B. Acyltransferase LRAT is the main enzyme that catalyzes vitamin A esterification . HRASLS enzymes are also referred to as LRAT-like proteins because of their sequence homology to LRAT .

The basic structural motif of the LRAT domain is composed of a four-strand antiparallel β-sheet and three α-helices. The longest α-helix (alpha3) is packed against the β-sheet, and the two other shorter α-helices are located on the sides. A highly conserved catalytic Cys, identified as the acylation site, is located near the N terminus of alpha3. This arrangement defines the active site location, which is embedded into a well defined groove formed by the extended loops between beta1-beta2, beta3-beta4, and the N terminus of the alpha3 helix. The side chain of the Cys is packed against a β-sheet core of the domain, placing it in close proximity to a conserved His from the beta2 strand. The β-sheet is spread open on one end allowing formation of a hydrogen bond between the His and the Cys. The third polar residue in this catalytic triad is a polar residue in the neighboring beta3 strand. The Cys residue was shown to act as a nucleophile and form a covalent thiol-acyl intermediate in the catalytic process .
Lysis protein S (Lysis_S)
Type: Family

This entry contains a family of small hydrophobic holin proteins with one or more transmembrane domains. Members of this family fall into the holin superfamily II, and Phage 21 S holin is the prototype for this superfamily. It has two transmembrane segments with both the N- and C-termini on the cytoplasmic side of the inner membrane in E. coli. Holins are a diverse family of proteins that cause bacterial membrane lysis during late-protein synthesis. It is thought that the temporal precision of holin-mediated lysis may occur through the build up of a holin oligomer which causes the lysis .
BON domain (BON_dom)
Type: Domain

The BON domain is typically ~60 residues long and has an α/β fold. There is a conserved glycine residue and several hydrophobic regions which suggests a binding function, and, actually, it contains a phospholipid-binding site

,

]. Most proteobacteria seem to possess one or two BON-containing proteins, typically of the OsmY-type proteins ; outside of this group the distribution is more disparate.

The OsmY protein is an Escherichia coli 20kDa outer membrane or periplasmic protein that is expressed in response to a variety of stress conditions, in particular, helping to provide protection against osmotic shock. One hypothesis is that OsmY prevents shrinkage of the cytoplasmic compartment by contacting the phospholipid interfaces surrounding the periplasmic space. The domain architecture of two BON domains alone suggests that these domains contact the surfaces of phospholipids, with each domain contacting a membrane .

In the potassium binding protein Kbp, this domain is able to bind K .

This domain is also found in ArfA, a membrane protein required for supporting bacterial growth in acidic environments .
DMSO reductase anchor subunit (DmsC) (DmsC)
Type: Family

The terminal electron transfer enzyme dimethyl sulphoxide reductase of Escherichia coli is a heterotrimeric enzyme composed of a membrane extrinsic catalytic dimer (DmsAB) and a membrane intrinsic polytopic anchor subunit (DmsC) . This family represents DmsC.