SII-SWORD/CoKE huggingface dataset:
Large tegument protein deneddylase (HSV_LTP)
Type: Family

All herpesviruses contain a Ubiquitin (Ub)-specific cysteine protease (USP) domain embedded within their large tegument protein. The herpesvirus tegument ubiquitin (Ub)-specific protease (htUSP) domain of ~200 amino acids adopts an α-β-α sandwich fold that features a central catalytic cleft, ideally suited to accommodate the C-terminal stretch of Ub. The catalytic triad Cys-His-Asp is strictly conserved, along with a putative oxyanion hole-forming Gln residue. The htUSP domain is a member of peptidase family C76 of clan CA .

BPLF1, the Epstein-Barr-virus-encoded member of this protease family, is a deneddylase that regulates virus production by modulating the activity of cullin-RING ligases. Homologues encoded by other herpesviruses share the deneddylase activity .
Proton/glutamate-aspartate symporter GltP (GltP)
Type: Family

GltP is a carrier protein of the Na(+)-independent, binding-protein-independent glutamate-aspartate transport system .
Large ribosomal subunit protein bL28/bL31-like superfamily (Ribosomal_bL28/bL31-like_sf)
Type: Homologous_superfamily

This superfamily includes ribosomal proteins with CxxC motifs, including bL28 and bL31 from the large subunit. In early ribosomal structures, L28p had been misinterpreted as L31p. In the ribosomal protein bL28 family there are sequences containing two CxxC pairs. Threading these sequences into this fold brings the four cysteines in a similar site to the zinc-binding site of glucocorticoid receptor-like zinc fingers. In the ribosomal protein bL31, there are also members with two CxxC pairs. However, these do not form a putative zinc-binding site in this fold.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Cytoplasmic envelopment protein 3 (HSV_CEP3_betahv)
Type: Family

This entry includes cytoplasmic envelopment protein 3 (or pp28) from herpesviruses. The pp28 protein from human cytomegalovirus is encoded by the UL99 gene. Protein pp28 is myristylated and found in the tegument of the virus particle . Mutation studies have shown that pp28 is essential for the virus to acquire is final membrane. The pp28 protein can be detected in a vesicle budded off from the Golgi, where the virus acquires its outer membrane . In order to be correctly localized, pp28 forms a complex with UL94 .
Cell division coordinator CpoB (CpoB)
Type: Family

CpoB coordinates the complexes involved in septal peptidoglycan synthesis (PBP1B-LpoB complex) and outer membrane constriction (Tol system). This coordination contributes to maintain the integrity of the cell envelope during division. CpoB localizes to the septum concurrent with PBP1B-LpoB and Tol at the onset of constriction and interacts with both complexes, regulating PBP1B activity in response to Tol energy state .
Envelope glycoprotein N (HSV_GN)
Type: Family

This entry represents viral glycoprotein N (also known as BLRF1, U46, 53, and UL73). These UL73-like envelope glycoproteins, which associate in a high molecular mass complex with their counterpart protein gM, induce neutralizing antibody responses in the host. These glycoproteins are highly polymorphic, particularly in the N-terminal region .
Envelope glycoprotein L (HSV_GL_alphagamma)
Type: Family

This entry includes envelope glycoprotein L (gL) from Herpesviruses. Glycoproteins H (gH) and L form a heterodimer which is required for the fusion of viral and plasma membranes enabling the virus to enter the host cell. In the complex, gH is inhibited until the complex binds to a host integrin and gL dissociates from the complex .
Ribitol-5-phosphate cytidylyltransferase (TarI)
Type: Family

Ribitol-5-phosphate cytidylyltransferase (TarI) is required for the synthesis of activated ribitol via the wall teichoic acid biosynthesis pathway. The enzyme catalyzes the transfer of the cytidylyl group of CTP to D-ribitol 5-phosphate to form CDP-ribitol .
Ribulose-5-phosphate reductase (TarJ)
Type: Family

TarJ is an NADPH-dependent alcohol dehydrogenase for the synthesis of ribitol 5-phosphate from ribulose 5-phosphate. Ribitol phosphate is a component of the cell wall teichoic acid in some bacteria, such as Streptococcus pneumoniae .
DNA replication helicase, Herpesvirus (HSV_HELI)
Type: Family

This entry contains Herpesviruse proteins that possesse helicase-like motifs and may function as the helicase subunit of the helicase/primase complex.
N-acetylglucosaminyldiphosphoundecaprenol N-acetyl-beta-D-mannosaminyltransferase (TagA_TarA)
Type: Family

TagA/TarA catalyzes the conversion of GlcNAc-PP-undecaprenol into ManNAc-GlcNAc-PP-undecaprenol . The tarA gene is part of an operon involved in the synthesis of the teichoic acid poly(glycerol phosphate) .
Ribonucleotide reductase small subunit, Herpesvirus (HSV_RIR2)
Type: Family

The beta (small) subunit of ribonucleotide reductase (RNR) is a member of a broad superfamily of ferritin-like diiron-carboxylate proteins.

This entry includes the ribonucleoside-diphosphate reductase small subunit from Herpesviruses.
Ribonucleoside-diphosphate reductase large subunit-like protein, Betaherpesviruses (HSV_RIR1_betahv)
Type: Family

Ribonucleotide reductase (RNR,

) catalyses the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in their genomes.

Ribonucleotide reductase is an oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain .

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals, the function of each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction process by hydrogen atom abstraction from the ribonucleotide . The radical-based reaction involves five cysteines: two of these are located at adjacent anti-parallel strands in a new type of ten-stranded α/β-barrel; two others reside at the carboxyl end in a flexible arm; and the fifth, in a loop in the centre of the barrel, is positioned to initiate the radical reaction . There are several regions of similarity in the sequence of the large chain of prokaryotes, eukaryotes and viruses spread across 3 domains: an N-terminal domain common to the mammalian and bacterial enzymes; a C-terminal domain common to the mammalian and viral ribonucleotide reductases; and a central domain common to all three .

This entry represents the ribonucleotide reductase large subunit from Betaherpesviruses.
Ribonucleotide reductase large subunit, Alphaherpesviruses (HSV_RIR1)
Type: Family

Ribonucleotide reductase (RNR,

) catalyses the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in their genomes.

Ribonucleotide reductase is an oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain .

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals, the function of each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction process by hydrogen atom abstraction from the ribonucleotide . The radical-based reaction involves five cysteines: two of these are located at adjacent anti-parallel strands in a new type of ten-stranded α/β-barrel; two others reside at the carboxyl end in a flexible arm; and the fifth, in a loop in the centre of the barrel, is positioned to initiate the radical reaction . There are several regions of similarity in the sequence of the large chain of prokaryotes, eukaryotes and viruses spread across 3 domains: an N-terminal domain common to the mammalian and bacterial enzymes; a C-terminal domain common to the mammalian and viral ribonucleotide reductases; and a central domain common to all three .

This entry represents the ribonucleotide reductase large subunit from Alphaherpesviruses.
Endolytic peptidoglycan transglycosylase RlpA (RlpA)
Type: Family

Rare lipoprotein A (RlpA) is an outer membrane protein that localises to the septal ring and scattered foci along the lateral wall in Escherichia coli. In Pseudomonas aeruginosa, RlpA is a lytic transglycosylase with preference for naked glycan strands that is needed for efficient separation of daughter cells and maintenance of rod shape .
Inhibitor of hydrogen peroxide resistance (IprA)
Type: Family

IprA (inhibitor of hydrogen peroxide resistance) is a protein conserved across Enterobacteriaceae. Its deletion results in increased resistance to oxidative stress .
Viral alkaline exonuclease (Viral_alk_exo)
Type: Family

This entry includes alkaline exonucleases from members of the Herpesviridae and Baculoviridae, both DNA-containing virus families .
Bacterial renalase (Bac_renal)
Type: Family

A bacterial form of renalase has been identified in Pseudomonas that has the same substrate specificity profile as human renalase, but with a marked preference for substrates derived from beta-NAD+. It catalyzes the oxidation of the 1,2-dihydro- and 1,6-dihydro- isomeric forms of beta-NAD(P) back to beta-NAD(P)+ . This could serve to protect dehydrogenase enzymes from inhibition by these isomers.
Succinate--CoA ligase [GDP-forming] subunit beta, mitochondrial (Succ_CoA_betaG_euk)
Type: Family

This entry includes the beta subunit of the mitochondrial, GTP-forming succinate--CoA ligase (SUCLG;

) from eukaryotes. The ligase functions in the citric acid cycle (TCA), and is a heterodimer of an alpha and beta subunit. It couples the hydrolysis of succinyl-CoA to the synthesis of GTP which is the only substrate-level phosphorylation step in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit. ATP-forming succinate--CoA ligase has the same alpha subunit but a different beta subunit .
Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial (Succ_CoA_betaA_euk)
Type: Family

This entry includes the beta subunit of the mitochondrial, ATP-forming succinate--CoA ligase (SUCLA;

) from eukaryotes. The ligase functions in the citric acid cycle (TCA), and is a heterodimer of an alpha and beta subunit. It couples the hydrolysis of succinyl-CoA to the synthesis of ATP which is the only substrate-level phosphorylation step in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit. GTP-forming succinate--CoA ligase has the same alpha subunit but a different beta subunit . Deficiency of SUCLA activity is associated with encephalomyopathy and mitochondrial DNA depletion .
Chromodomain-helicase-DNA-binding protein 8 (CHD8)
Type: Family

This entry includes chromodomain-helicase-DNA-binding protein 8 (CHD8) from animals. CHD8 regulates transcription. It acts as a repressor in several pathways: repressing transcription by remodeling chromatin structure (binding to histone H3 di- and trimethylated on Lys4) and recruiting histone H1 to target genes ; suppressing p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity ; and a negative regulator of Wnt signaling pathway, regulating beta-catenin activity . By interacting with CTCF, it is involved in epigenetic remodeling . CHD8 can also act as a transcription activator, participating in efficient U6 RNA polymerase III transcription by interacting with ZNF143. Gene knockout is embryonically lethal . CHD8 has been linked to autism spectrum disorder (ASD) .
E3 ubiquitin-protein ligase RNF168 (RNF168)
Type: Family

RNF168 is a RING-type ubiquitin E3 ligases with roles in the DNA damage response to double-strand breaks (DSBs). It works in concert with another RING-type ubiquitin E3 ligase, RNF8, targeting histones H2A and H2AX. RNF168 amplifies the RNF8-dependent H2A ubiquitination of K-63, promoting the formation ubiquitin conjugates that contribute to the ubiquitin-dependent signals necessary for recruitment of downstream regulators of the DSB response pathway . Interestingly, RNF168 also catalyses H2A monoubiquitination on K13-15; this seems to be the first step of H2A ubiquitination that drives the DNA damage signaling .
Scavenger receptor class A member 5 (SCARA5)
Type: Family

Scara5 is a ferritin receptor that mediates non-transferrin iron delivery. It binds serum ferritin and then stimulates its endocytosis from the cell surface. It was identified as a cell type-specific alternatively mechanism of iron traffic during organogenesis . It has been classified as belonging to class A scavenger receptors .
Kintoun (Kintoun)
Type: Family

Kintoun (also known as ktu or dynein assembly factor 2, axonemal) is a cytoplasmic protein conserved from ciliated unicellular organisms to mammals. It is required for cytoplasmic pre-assembly of axonemal dynein arm complexes before intraflagellar transport loads them for the ciliary compartment. Its homologue in single-celled alga Chlamydomonas is known as PF13. A mutation in Ktu/PF13 has been identified in some patients with primary ciliary dyskinesia (PCD). In the absence of Ktu/PF13, both dynein arms (inner and outer) are missing or defective in the axoneme, leading to a loss of motility .
Peptidase A3B domain (Peptidase_A3B)
Type: Domain

This entry includes the aspartic peptidase domain from the P3 polyprotein of Pararetroviruses (such as rico tngro bacilliform virus), a member of the family Caulimoviridae. P3 contains a putative movement protein (MP), the capsid protein (CP), the aspartate protease (PR) and the reverse transcriptase (RT) with a ribonuclease H activity. PR proteolytically processes P3. The sequence DSGS is believed to be the RTBV protease active site . The RTBV PR domain forms peptidase family A3 subfamily B .
Zinc finger CCHC HIVEP-type (Znf_CCHC_HIVEP)
Type: Domain

The entry includes the HIVEP-type CCHC zinc finger. The HIVEP family of zinc finger (Znf) proteins regulates a diverse array of developmental and biological processes through direct DNA binding, as well as interaction with other transcription factors and components of signal transduction pathways. Three vertebrate paralogous genes have been identified, HIVEP (also called ZAS or Shn)-1, -2 and -3, as well as the closely related Drosophila gene, Schnurri. HIVEP and the Drosophila Schnurri proteins contain two pairs of C2H2 Znf and, with the exception of the HIVEP2 family, a conserved CCHC-type Znf. In addition, Drosophila Schnurri contains a conserved carboxyl-terminal Znf triplet that is not found in the vertebrate members. Sequence conservation between vertebrate HIVEP and the Drosophila Schnurri proteins is generally low with the exception of the two pairs of C2H2 Znf, which are highly conserved .
ATP-dependent RNA helicase DHX29 (DHX29)
Type: Family

ATP-dependent RNA helicase DHX29 is a DExH-box protein involved in eukaryotic translation initiation. Eukaryotic translation initiation begins with assembly of a 43S preinitiation complex which then attaches to the mRNA and starts scanning the 5'-UTR to the initiation codon. DHX29 is required to bind to the 40S subunit of the 43S preinitiation complex to allow highly structured 5'-UTRs to be scanned. DHX29 has been shown to hydrolyze ATP, GTP, UTP and CTP, and promotes 48S complex formation .
Zinc finger CCHC FOG-type (Znf_CCHC_FOG)
Type: Domain

This entry includes the FOG-type CCHC zinc finger.

Zinc fingers (Znfs) are among the most common of all protein domains. They have traditionally been regarded as sequence-specific DNA-binding motifs. However it has also become apparent that many Znfs mediate specific protein-protein interactions. Transcriptional cofactors of the Friend of GATA (FOG) family are diverse in sequence but their individual Znf regions share considerable homology. They contain either eight or nine Znfs that are related to the classical CCHH Znfs (which have a conserved C-X(2,5)-C-X(12)-H-X(2,5)-H sequence). Several of the fingers in each FOG protein, however, have an altered consensus sequence in which the final zinc binding histidine is replaced with a cysteine. It is only these variant CCHC ZbFs that mediate interactions with GATA N-terminal zinc fingers (NFs) .

The FOG-type CCHC zinc finger comprises a short β hairpin followed by an α helix. It resembles classical CCHH fingers in structure. The only notable difference is a short extended portion of the polypeptide backbone before the fourth zinc ligand. Two of the residues implicated in GATA binding are located on the extended portion of the backbone, immediately preceding the final cysteine. Thus, the CCHC topology appears to play a key role in facilitating the interaction. The residues that are implicated in GATA binding are largely conserved across FOG family CCHC Znfs, although three of the residues that affect the binding affinity show some variation .

Some proteins known to contain a FOG-type CCHC zinc finger are listed below:

Vertebrate Friend of GATA-1 (FOG-1), a zinc finger protein that interacts physically with the erythroid DNA-binding protein GATA-1 and modulates its transcriptional activity.

Mammalian FOG-2, associates with GATA-1 and other mammalian GATA factors.

Drosophila melanogaster U-shaped (Ush), interacts with the GATA factors Pannier and Serpent to control development in the fly.
Extended PHD (ePHD) domain (EPHD)
Type: Domain

The extended plant homeodomain (ePHD) domain contains an N-terminal pre-PHD (C2HC zinc finger), a long linker, and a noncanonical PHD finger (C4HC3 zinc finger). The ePHD domain can bind dsDNA but not histones .

The pre-PHD-type C2HC zinc finger and the PHD finger in the ePHD domain are associated with each other via extensive hydrophobic interactions and numerous hydrogen bonding interactions and folded as an intact structural module. The pre-PHD-type C2HC zinc finger consists of two α-helices separated by an anti-parallel β-sheet. Three cysteine residues and one histidine residue from the N-terminal loop, β2-strand, and α2-helix coordinate one zinc ion (designated Zn1). The C-terminal part of the ePHD domain is a PHD finger, consisting of one short antiparallel β-sheet and one long antiparallel β-sheet that are linked by one α-helix. Like other PHD fingers, the PHD finger of the ePHD domain consists of two interleaved zinc fingers. A pair of bound zinc ions (designated Zn2 and Zn3) specifically stabilizes the characteristic cross-braced folding topology of the PHD finger. Each zinc ion is coordinated by a combination of four cysteine and histidine residues in which the Zn3 ion is coordinated by a C3H motif instead of a C4 motif .

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

Vertebrate plant homeodomain finger 6 (PHF6), a multidomain protein that comprises four nuclear localization signals and two ePHD domains. It is implicated in chromatin regulation and neural development.

Vertebrate MLL1/2/3/4, histone methyltransferases.

Vertebrate JMJD2A/B/C, histone demethylases.

Vertebrate Bromodomain- and PHD finger-containing protein 1, 2, and 3 (BRPF1/2/3), a component of MOZ (monocytic leukemia zinc finger)/MORF (MOZ- related factor) histone acetyltransferase complex.

Vertebrate JADE1/2/3, components of the HBO1 complex which has a histone H4-specific acetyltransferase activity.

AF10/17, subunits of the multimeric DOT1L complex that mediates H3K79 methylation.

Caenorhabditis elegans
protein lin-49, a component of a histone modifying complex.

Yeast NuA3 HAT complex component NTO1.
Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta (AcCoA_carboxyl_beta)
Type: Domain

All of the members in this family are biotin dependent carboxylases . The carboxyl transferase domain carries out the following reaction; transcarboxylation from biotin to an acceptor molecule. There are two recognised types of carboxyl transferase. One of them uses acyl-CoA and the other uses 2-oxoacid as the acceptor molecule of carbon dioxide. All of the members in this family utilise acyl-CoA as the acceptor molecule.

In bacteria, the acetyl coenzyme A carboxylase (ACC) is a complex consisting of two subunits: alpha and beta. This domain also recognizes the bacterial ACC beta-subunit.