SII-SWORD/CoKE huggingface dataset:
AAR2, C-terminal domain (AAR2_C)
Type: Domain

This entry consists of the C-terminal domain of eukaryotic Aar2 and Aar2-like proteins. This domain consists of 9 α-helices, 1 π-helix and 1 3(10)-helix.

Aar2 is a U5 small nuclear ribonucleoprotein (snRNP) particle assembly factor and part of Prp8, which forms a large complex containing U5 snRNA, Snu114, and seven Sm proteins (B, D1, D2, D3, E, F and G). Upon import of the complex into the nucleus, Aar2 phosphorylation leads to its release from Prp8 and replacement by Brr2p, thus playing an important role in Brr2p regulation and possibly safeguarding against non-specific RNA binding to Prp8 . Aar2p binds directly with the RNaseH-like domain in the C-terminal region of Prp8p . In yeast, Aar2 protein is involved in splicing pre-mRNA of the a1 cistron and other genes important for cell growth .
LigD polymerase domain, MtLigD-type (MtLigD_Pol-like)
Type: Domain

This entry represents the polymerase (Pol) domain of bacterial LigD proteins similar to Mycobacterium tuberculosis (Mt)LigD.

The LigD Pol domain belongs to the archaeal/eukaryal primase (AEP) superfamily . In prokaryotes, LigD along with Ku is required for non-homologous end joining (NHEJ)-mediated repair of DNA double-strand breaks (DSB) . NHEJ-mediated DNA DSB repair is error-prone. MtLigD is monomeric and contains an N-terminal Pol domain, a central phosphoesterase module, and a C-terminal ligase domain. It has been suggested that LigD Pol contributes to NHEJ-mediated DNA DSB repair in vivo, by filling in short 5'-overhangs with ribonucleotides; the filled in termini would then be sealed by the associated LigD ligase domain, resulting in short stretches of RNA incorporated into the genomic DNA. The MtLigD Pol domain is stimulated by manganese, is error-prone, and prefers adding rNTPs to dNTPs in vitro. The MtLigD Pol domain has been shown to prefer DNA gapped substrates containing a 5'-phosphate group at the gap .
Large ribosomal subunit protein mL46, NUDIX domain (Ribosomal_mL46_NUDIX)
Type: Domain

Mitochondrial ribosomal protein mL46 (also known as MRPL46) is a component of the large subunit (39S) of the mammalian mitochondrial ribosome and a member of the Nudix hydrolase superfamily. MRPs are thought to be involved in the maintenance of the mitochondrial DNA. In general, members of the Nudix superfamily require a divalent cation, such as Mg2+ or Mn2+, for activity and contain the Nudix motif, a highly conserved 23-residue block (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. MRP L46 appears to contain a modified NUDIX motif .

This entry represents the NUDIX motif-containing domain of mL46 from vertebrates.
LigD polymerase domain, PaeLigD-type (PaeLigD_Pol-like)
Type: Domain

This entry represents the polymerase (Pol) domain of bacterial LigD proteins similar to Pseudomonas aeruginosa (Pae) LigD.

The LigD Pol domain belongs to the archaeal/eukaryal primase (AEP) superfamily. In prokaryotes, LigD along with Ku is required for non-homologous end joining (NHEJ)-mediated repair of DNA double-strand breaks (DSB). NHEJ-mediated DNA DSB repair is error-prone. PaeLigD is monomeric, containing an N-terminal phosphoesterase module, a central polymerase (Pol) domain, and a C-terminal ATP-dependent ligase domain. It has been suggested that LigD Pol contributes to NHEJ-mediated DNA DSB repair in vivo, by filling in short 5'-overhangs with ribonucleotides; the filled in termini would then be sealed by the associated LigD ligase domain, resulting in short stretches of RNA incorporated into the genomic DNA. The PaeLigD Pol domain in vitro, in a manganese-dependent fashion, catalyzes templated extensions of 5'-overhang duplex DNA, and nontemplated single-nucleotide additions to blunt-end duplex DNA; it preferentially adds single ribonucleotides at blunt DNA ends. PaeLigD Pol adds a correctly paired rNTP to the DNA primer termini more rapidly than it does a correctly paired dNTP; it has higher infidelity as an RNA polymerase than it does as a DNA polymerase, which is in keeping with the mutagenic property of NHEJ-mediated DNA DSB repair .
LigD polymerase domain, type 3 (LigD_Pol-like_3)
Type: Domain

This entry represents a subgroup of polymerase (Pol) domains of bacterial LigD proteins. The LigD Pol domain belongs to the archaeal/eukaryal primase (AEP) superfamily. In prokaryotes, LigD along with Ku is required for non-homologous end joining (NHEJ)-mediated repair of DNA double-strand breaks (DSB)
. NHEJ-mediated DNA DSB repair is error-prone . It has been suggested that LigD Pol contributes to NHEJ-mediated repair DSB repair in vivo, by filling in short 5'-overhangs with ribonucleotides; the filled in termini would then be sealed by the associated LigD ligase domain, resulting in short stretches of RNA incorporated into the genomic DNA . The Pol domains of Pseudomonas aeruginosa (PaeLigD;

) and Mycobacterium tuberculosis (MtLigD;

) are stimulated by manganese, are error-prone, and prefer adding rNTPs to dNTPs in vitro. However, this subgroup of domains is distinct from PaeLigD and MtLigD, and awaits functional characterization.
NTP pyrophosphohydrolase, DR2231-like (NTP-PPase_DR2231-like)
Type: Family

This family includes a MazG-like NTP-PPase from Deinococcus radiodurans (DR2231), a putative NTP-PPase YP_001813558.1 from Exiguobacterium sibiricum and their bacterial homologues. DR2231 shows significant structural resemblance to MazG proteins, but is functionally related to the dimeric dUTPases . It can hydrolyze dUTP into dUMP. DR2231-like proteins contain a well conserved divalent ion binding motif, EXXEX(12-28)EXXD, which is the identity signature for the all-α-helical NTP-PPase superfamily. Unlike normal dimeric dUTPase-like proteins with a central four-helix bundle forming the active site, YP_001813558.1 displays a very unusual interlaced segment-swapped dimer. It potentially prefers to hydrolyze dCTPs or its derivatives. YP_001813558.1-like proteins contain a variant divalent ion binding motif, EXXEX(12-28)AXXD .
Sialidase, Influenza viruses A/B (Sialidase_Influenza_A/B)
Type: Domain

Sialidases or neuraminidases function to bind and hydrolyze terminal sialic acid residues from various glycoconjugates . Viral neuraminidases, such as this family from Influenza viruses A and B, play a vital role in pathogenesis. Influenza neuraminidase cleaves an alpha-ketosidic linkage between sialic acid and a neighbouring sugar residue . During budding of virus particles from the infected cell, the sialidase helps to prevent the newly formed viral particles from aggregating. The viral sialidase cleaves terminal sialic acid from glycan structures on the infected cell surface, promoting virus release and the spread of virus to neighbouring cells that are not yet infected. Also, sialidase modifies mucins in the respiratory tract and may improve access of the viral particle to its target cells. Sialidases have a six-bladed β-propeller fold .
RelA/SpoT, TGS domain (TGS_RelA/SpoT)
Type: Domain

RelA/SpoT homologue (RSH) proteins play a central role in bacterial stringent response. RelA (also referred to as ppGpp hydrolase/synthetase) and SpoT are activated during stress conditions and synthesize transcriptional modulators (p)ppGpp that allow bacteria to adapt to this condicions. They contain a TGS domain, named after the Threonyl-tRNA Synthetase, GTPase, and SpoT proteins where it occurs . This domain of RelA binds the CCA tail to orient the free 3' hydroxyl group of the terminal adenosine towards a β-strand, thus an aminoacylated tRNA at this position would be sterically impeded. This association suppresses auto-inhibition and activates the synthesis of (p)ppGpp and initiates the stringent response. .
Histidyl-anticodon-binding (HisRS_anticodon)
Type: Domain

Histidyl-tRNA synthetase (HisRS) belongs to class II aminoacyl-tRNA synthetases (aaRS) . This entry represents the anticodon binding domain, which is responsible for specificity in tRNA-binding, so that the activated amino acid is transferred to a ribose 3' OH group of the appropriate tRNA only.
Glutaredoxin, PICOT-like (GRX_PICOT-like)
Type: Domain

This entry represents a glutaredoxin (GRX) domain found in PICOT (also known as glutaredoxin-3 or PKC-interacting cousin of thioredoxin) and GRX-PICOT-like proteins. The non-PICOT members of this group contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contains three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium-independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity . Characterised non-PICOT proteins with this domain include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum .
Phosphatidylserine decarboxylase, eukaryotic type 1 (PSD_type1_euk)
Type: Family

A non-mitochondrial type I phosphatidylserine decarboxylase has been identified in Plasmodium falciparum .

This entry represents the eukaryotic type 1 subfamily.

Phosphatidylserine decarboxylase plays a pivotal role in the synthesis of phospholipid by the mitochondria. The substrate phosphatidylserine is synthesized extramitochondrially and must be translocated to the mitochondria prior to decarboxylation .
Phosphatidylserine decarboxylases

is responsible for conversion of phosphatidylserine to phosphatidylethanolamine and plays a central role in the biosynthesis of aminophospholipids .

Phosphatidylserine decarboxylases (PSDs) have been classified in two types. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha and beta subunits .
Tripartite terminase subunit 3 (HSV_TRM3)
Type: Family

This family includes proteins that are required for DNA packing in viruses of the Herpesviridae family. The tripartite terminase is a complex of three subunits, (TRM1, TRM2 and TRM3) that forms in the host cytoplasm. The complex moves to the host nucleus where it interacts with the capsid portal vertex, which forms a ring permitting genomic DNA to translocate to the viral capsule. Subunit TRM3 (also known as UL15) is an RNase H-like nuclease that cleaves concatenated viral DNA into unit length genomes .
tRNA 5-carboxymethoxyuridine methyltransferase (Cmo5U_methylTrfase)
Type: Family

Post-transcriptional modifications at the anticodon first (wobble) position of tRNA play critical roles in precise decoding of genetic codes.
tRNA 5-carboxymethoxyuridine (cmo5U) methyltransferase (also known as CmoM and SmtA), is a Class I S-adenosyl-L-methionine-dependent methyltransferase (SAM MTase). It methylates cmo5U to form mcmo5U (5-methoxycarbonylmethoxyuridine) in the presence of S-Adenosyl methionine (AdoMet). This terminal methylation of mcmo5U contributes to the decoding ability of tRNA(Ala1) .

CmoM may form a homodimer, with each subunit containing one molecule each of AdoMet, sulfate, acetate and 2-mercaptoethanol as ligands. Highly conserved residues in the catalytic centre are thought to be essential for normal methyltransferase activity .
D-aminoacyl-tRNA deacylase DTD3 (Deacylase_DTD3)
Type: Family

D-aminoacyl-tRNA deacylase (also known as D-tyrosyl-tRNA deacylase or DTD) helps cells to counteract the accumulation of harmful D-aminoacyl-tRNAs by removing D-aminoacyl moieties from the 3'-end of tRNA. Three distinct deacylases have been discovered: DTD1 is predicted to occur in most bacteria and eukaryotes, DTD2 has homologues in most archaea and in plants, and DTD3 is found in cyanobacteria .

This entry represents DTD3. DTD3 behaves as a metalloenzyme and has been shown to confer resistance against D-tyrosine .
Nucleoside permease NupG (NupG)
Type: Family

Nucleoside permease NupG is a member of the nucleoside:H+ symporter (NHS) family . NupG can transport a wide range of nucleosides and deoxynucleosides . It can also transport xanthosine, but with a very low affinity .
Regulatory protein E2 (Reg_prot_E2)
Type: Family

Regulatory protein E2 exists as a homodimer and interacts with a homodimer of E1 to improve the specificity of the DNA binding of E1. Once the complex is bound to DNA, E2 is released . E2 also binds to the E2RE response element (5'-ACCNNNNNNGGT-3'), which is present in multiple copies in the viral genome. Binding of E2 to this element either activates or represses transcription .
Fused isobutyryl-CoA mutase (IcmF)
Type: Family

G-protein metallochaperones ensure fidelity during cofactor assembly for a variety of metalloproteins, including adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase. IcmF is a natural fusion protein of AdoCbl-dependent isobutyryl-CoA mutase and its corresponding G-protein chaperone . It exhibits both GTPase activity and AdoCbl-dependent isomerase activity, interconverting isobutyryl-CoA and n-butyryl-CoA. It can also interconvert pivalyl-CoA and isovaleryl-CoA, albeit with low efficiency, which has biotechnological potential . IcmF structure has been reported .
Elongation of very long chain fatty acids protein 7 (ELOVL7)
Type: Family

Elongation of very long chain fatty acids protein 7 (ELOVL7, also known as Very long chain fatty acid elongase 7) is an enzyme of the long-chain fatty acid elongation cycle . It is a transmembrane protein found in the endoplasmic reticulum with the active site within one of the transmembrane regions. ELOVL7 adds two carbons per cycle to the chains of long and very long fatty acids with higher activity towards C18 acyl-CoAs. ELOVL7 has been implicated in prostate cancer growth and the gene is regulated by the androgen pathway through SREBP1 .
tRNA (guanosine(18)-2'-O)-methyltransferase (TrmH)
Type: Family

tRNA (guanosine(18)-2'-O)-methyltransferase (also known as tRNA [Gm18] methyltransferase, and TrmH) catalyses the 2'-O methylation of guanosine at position 18 (Gua18) in the D loop of tRNA . In the reaction, S-adenosyl-L-methionine (AdoMet) functions as a methyl group donor and is converted to S-adenosyl-L-homocysteine (AdoHcy). The methylation of tRNA nucleotides helps to stabilize the L-shaped tRNA structure and improve their molecular recognition .

TrmH enzymes can be classified into two types based on their substrate tRNA specificity. Type I TrmH, which includes Thermus thermophilus TrmH, can modify all tRNA species. Type II TrmH, which includes Echerichia coli TrmH and Saccharomyces cerevisiae TrmH, modifies only a subset of tRNA species .
(4S)-4-hydroxy-5-phosphonooxypentane-2,3-dione isomerase (LsrG)
Type: Family

Autoinducers are signal molecules involved in quorum sensing, the process of chemical communication that bacteria use to assess cell population density and synchronize behaviour. The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2).

A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the lsr operon, induced by AI-2. This operon consists of a transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes that are responsible for processing the phosphorylated signal, thereby terminating induction of the lsr operon .

LsrG catalyzes the conversion of (4S)-4-hydroxy-5-phosphonooxypentane-2,3-dione (P-DPD) to 3-hydroxy-5-phosphonooxypentane-2,4-dione (P-HPD) .
3-hydroxy-5-phosphonooxypentane-2,4-dione thiolase (LsrF)
Type: Family

Autoinducers are signal molecules involved in quorum sensing, the process of chemical communication that bacteria use to assess cell population density and synchronize behaviour. The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2).

A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the lsr operon, induced by AI-2. This operon consists of a transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes that are responsible for processing the phosphorylated signal, thereby terminating induction of the lsr operon .

One of the enzymes responsible for processing the phosphorylated signal is LsrF. LsrF catalyzes the transfer of an acetyl moiety from 3-hydroxy-5-phosphonooxypentane-2,4-dione to CoA to form glycerone phosphate and acetyl-CoA .
Thioredoxin/glutathione peroxidase BtuE (BtuE)
Type: Family

Thioredoxin/glutathione peroxidase BtuE is a non-specific peroxidase that can use thioredoxin or glutathione as a reducing agent .

In vitro, BtuE preferentially utilises thioredoxin A or C to decompose hydrogen peroxide as well as cumene, tert-butyl, and linoleic acid hydroperoxides. Thus, it has been suggested that lipid peroxides could be the real, physiological substrates of BtuE .
Elongation of very long chain fatty acids protein 6 (ELOVL6)
Type: Family

Elongation of very long chain fatty acids protein 6 (ELOVL6, also known very long chain fatty acid elongase 6) is a membrane-bound enzyme located in the endoplasmic reticulum that is component of the long-chain fatty acids elongation cycle . ELOVL6 adds two carbons per cycle to long- and very long-chain fatty acids with a preference for 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs .
Autoinducer-2 kinase (AI-2_kinase)
Type: Family

Autoinducers are signal molecules involved in quorum sensing, the process of chemical communication that bacteria use to assess cell population density and synchronize behaviour. The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2).

A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the lsr operon, induced by AI-2. This operon consists of a transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes that are responsible for processing the phosphorylated signal, thereby terminating induction of the lsr operon .

Autoinducer-2 kinase (also known as LsrK) phosphorylates AI-2. Phosphorylation serves to trap and activate AI-2 within the cell . Phosphorylated AI-2 (phospho-DPD) binds and inactivates the transcriptional repressor protein LsrR thereby inducing the expression of the lsr operon and potentially other LsrR-regulated, quorum sensing-related genes .
Elongation of very long chain fatty acids protein 5 (ELOVL5)
Type: Family

Elongation of very long chain fatty acids protein 5 (ELOVL5) is a component of the the long-chain fatty acids elongation cycle. It is a transmembrane enzyme in the endoplasmic reticulum that adds two carbons per cycle to long- and very long-chain fatty acids with a preference for polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA .
Elongation of very long chain fatty acids protein 4 (ELOVL4)
Type: Family

Elongation of very long chain fatty acids protein 4 (ELOVL4, also known as very long chain fatty acid elongase 4) is a component of the the long-chain fatty acids elongation cycle. It is a transmembrane enzyme in the endoplasmic reticulum that adds two carbons per cycle to long- and very long-chain fatty acids with a preference for elongating C24:0 and C26:0 acyl-CoAs .
Elongation of very long chain fatty acids protein 3 (ELOVL3)
Type: Family

Elongation of very long chain fatty acids protein 3 (ELOVL3, also known as very long chain fatty acid elongase 3) is a component of the the long-chain fatty acids elongation cycle . It is a transmembrane enzyme in the endoplasmic reticulum that adds two carbons per cycle to long- and very long-chain fatty acids with a higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs .
Elongation of very long chain fatty acids protein 2 (ELOVL2)
Type: Family

Elongation of very long chain fatty acids protein 2 (ELOVL2, also known as very long chain fatty acid elongase 2) is a component of the the long-chain fatty acids elongation cycle . It is a transmembrane enzyme in the endoplasmic reticulum that adds two carbons per cycle to long- and very long-chain fatty acids acting on polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. It catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA), acting specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA.
Elongation of very long chain fatty acids protein 1 (ELOVL1)
Type: Family

Elongation of very long chain fatty acids protein 1 (ELOVL1, very long chain fatty acid elongase 1) is a component of the the long-chain fatty acids elongation cycle . It is a transmembrane enzyme in the endoplasmic reticulum that catalyses the elongation of saturated and monounsaturated C22-C26-VLCFAs (very long-chain fatty acids) . Mutations in this enzyme cause ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy .
Palmitoyltransferase PFA4 (PFA4)
Type: Family

Palmitoyltransferase PFA4 mediates the reversible addition of palmitate to target proteins, allowing them to associate with membranes . Saccharomyces cerevisiae PFA4 has been shown to palmitoylate several amino acid permeases , and to palmitoylate chitin synthase CHS3, which is required for its proper export from the ER .
Tyrosine recombinase XerH (XerH)
Type: Family

Bacteria with circular chromosomes generally contain site-specific tyrosine Xer recombinases that act at cognate dif sites near where replication terminates and resolve chromosome dimers to free monomers. Helicobacter pylori, Campylobacter and other members of H. pylori's epsilon subgroup of Gram-negative proteobacteria seem to contain just a single Xer recombinase, XerH . XerH, FtsK and an intact difH sequence are required for site-specific recombination at difH sites in H. pylori .
Protein-lysine N-methyltransferase EFM6 (EFM6)
Type: Family

Protein-lysine N-methyltransferase EFM6 is an S-adenosyl-L-methionine-dependent enzyme that methylates elongation factor 1-alpha (TEF1 and TEF2) at a lysine residue .
DNA primase (HSV_PRIM)
Type: Family

DNA primase (UL70) is the essential primase component of the helicase/primase complex which unwinds the DNA at replication forks and generates single-stranded DNA for both leading and lagging strand synthesis. The helicase/primase is a complex of UL70, UL102 (a component with no known function) and UL105 (the helicase) . The primase initiates primer synthesis and thereby produces large amount of short RNA primers on the lagging strand that the polymerase elongates using dNTPs. UL70 activity relies upon two aspartic acid residues .
Tyrosine recombinase XerA (XerA)
Type: Family

XerA is a site-specific tyrosine recombinase found in archaea. It displays the canonical two-domain structure of tyrosine-recombinases (with the two-domains folded as a C-shaped clamp) and assembles as an apo-dimer .

XerA is most likely used for chromosome dimer resolution in archaea, and it thought to bind to the dif site .