SII-SWORD/CoKE huggingface dataset:
Putative glycosyltransferase CHP04372 (Glycosyl_04372)
Type: Domain

This domain occurs in proteins of various lengths, in contexts that include O-antigen biosynthesis regions of various Leptospira species. It shows distant sequence similarity to family 9 glycosyltransferases (

), including ADP-heptose:LPS heptosyltransferase (RfaF), an enzyme involved in LPS inner core region biosynthesis.
EgtB-related enzyme signature domain (EgtB_signatur)
Type: Domain

This entry represents a signature C-terminal region of a distinct clade in the EgtB subfamily, other members of which participate in ergothioneine biosynthesis .
Hercynine metabolism small protein (Small_EgtBD)
Type: Family

Hercynine is the betaine (trimethylated amino group) form of histidine. It is the precursor of ergothioneine, a thiourea derivative containing a sulfur atom in the imidazole ring. This small protein occurs in a conserved four-gene cyanobacterial cassette along with an EgtD, the methyltransferase that converts histidine to hercynine as in ergothioneine biosynthesis, and an EgtB homologue, likely to attach some thiol through its sulfur to the hercynine imidazole ring.
Quinoprotein relay system zinc metallohydrolase 1 (SoxH-rel_PQQ_1)
Type: Family

By homology, members of this family are Zn metallohydrolases in the same family as the SoxH protein associated with sulfate metabolism, Bacillus cereus beta-lactamase II (see PDB:1bc2), and, more distantly, hydroxyacylglutathione hydrolase (glyoxalase II). All members occur in genomes with both PQQ biosynthesis and a PQQ-dependent (quinoprotein) dehydrogenase that has a motif of two consecutive Cys residues (

). The Cys-Cys motif is associated with electron transfer by specialised cytochromes such as c551. All these genomes also include a fusion protein (

) whose domains resemble SoxY and SoxZ from thiosulfate oxidation. A conserved Cys in this fusion protein aligns to the Cys residue in SoxY that carries sulfur cycle intermediates. In many genomes, the genes for PQQ biosynthesis enzymes, PQQ-dependent enzymes, their associated cytochromes, and members of this family are clustered. Note that one to three closely related Zn metallohydrolases may occur; this family represents a specific clade among them.
Hercynine metabolism protein (Cyano_EgtBD)
Type: Family

Hercynine is the betaine (trimethylated amino group) form of histidine. It is the precursor of ergothioneine, a thiourea derivative containing a sulfur atom in the imidazole ring. This protein occurs in a conserved four-gene cyanobacterial cassette along with an EgtD, the methyltransferase that converts histidine to hercynine as in ergothioneine biosynthesis, an EgtB homologue that is likely to attach some thiol (e.g. gamma-glutamyl-cysteine) through its sulfur to the hercynine imidazole ring, and a small protein of unknown function (

). Members are distantly related to phage shock protein A (PspA).
Small integral membrane protein (Mollicut_2TM)
Type: Family

Members of this family occur in Mycoplasma mycoides and two species of Spiroplasma. The protein is small and hydrophobic with two predicted transmembrane (TM) regions.
Selenouridine synthase, SelU C-terminal-like subunit (Arch_SelU_Cterm)
Type: Family

This protein is involved in biosynthesis of a selenonucleotide, probably 2-selenouridine, in tRNA of some archaea, such as Methanococcus maripaludis. This protein resembles the C-terminal region of bacterial SelU .
Conserved hypothetical protein CHP04376 (CHP04376)
Type: Family

Members of this protein family resemble

and, more distantly, phage shock protein A (PspA). Members are mostly restricted to the Cyanobacteria.
3,5/4-Trihydroxycyclohexa-1,2-dione hydrolase (Myo_inos_IolD)
Type: Family

Members of this protein family, 3,5/4-trihydroxycyclohexa-1,2-dione hydrolase (IolD), represent one of eight enzymes in a pathway converting myo-inositol to acetyl-CoA. IolD hydrolyses the cyclic molecule 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione to yield 5-deoxy-D-glucuronic acid. TPP (thiamine pyrophosphate) is a cofactor .
Selenouridine synthase, SelU N-terminal-like subunit (Arch_SelU_Nterm)
Type: Family

This protein is involved in biosynthesis of a selenonucleotide, probably 2-selenouridine, in tRNA of some archaea, such as Methanococcus maripaludis. This protein resembles the N-terminal region of bacterial SelU .
Outer membrane exchange protein TraA, N-terminal domain (Myxo_TraA_N)
Type: Domain

In Myxococcus xanthus, the TraA (MXAN_6895) and TraB (MXAN_6898) proteins (encoded within the traAB operon) serve as a bacterial transfer system required for contact-dependent exchange of outer membrane proteins. They are required in both donor and recipient cells. This entry represents the N-terminal domain of TraA. This domain is suggested to be similar to the PA14 domain (

); the processed PA14 domain may serve as a receptor for ligand binding .
Outer membrane beta-barrel protein, Proteobacteria (OMP_myx_plus_Proteobacteria)
Type: Domain

Proteins containing this domain are putative outer membrane β-barrel proteins from Proteobacteria. They are inferred by distant homologies to other families (e.g.

) and by the concentration of aromatic residues, especially Phe, in the OMP signal region.
Synergist-CTERM sorting domain (Synergist_CTERM)
Type: Domain

This entry represents a 27 residue domain containing features such as: 1) a short Gly/Ser-rich region that ends in an invariant Gly-Cys motif, 2) a highly hydrophobic probable transmembrane α helix with a nearly invariant Pro near the end, and 3) a cluster of basic residues (Arg, Lys), and then the end of the protein.
MXAN_4361/MXAN_4362 family small protein (MXAN_4361/MXAN_4362)
Type: Family

Members of this family are small proteins that appear to be restricted to and yet universal in the Myxococcales. The function is unknown. Members include two tandem loci in Myxococcus xanthus DK 1622, MXAN_4361 and MXAN_4362, although members are not in tandem in other Myxococcales.
IolE/MocC family (IolE/MocC)
Type: Family

Members of this family include the enzyme myo-inosose-2 dehydratase, product of the gene iolE, found in inositol utilisation cassettes in many species, and MocC, involved in rhizopine (L-3-O-methyl-scyllo-inosamine) catabolism in Rhizobium . Rhizopine is an inositol derivative.

IolE catalyses the dehydration of inosose (2-keto-myo-inositol, 2KMI or 2,4,6/3,5-pentahydroxycyclohexanone) to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione (D-2,3-diketo-4-deoxy-epi-inositol) .
Uncharacterised protein family CHP04562 (CHP04562)
Type: Family

Members of this family are proteins of unknown function, about 400 amino acids in length. Members are universal among the Myxococcales (a branch of the Deltaproteobacteria) and occur sporadically elsewhere.
Integral membrane protein (Integral_membrane)
Type: Family

Members of this protein are short (about 85-residue), low-complexity sequences of unknown function, with a highly hydrophobic N-terminal region of about 40 amino acids followed by a charged (Asp, Glu, Lys, and Arg-rich), sometimes repetitive C-terminal region. Members occur exclusively among the Mollicutes (Mycoplasma, Mesoplasma, Acholeplasma, Spiroplasma, Entomoplasma). The gene neighbourhood of this protein is not conserved.
Small ribosomal subunit protein bTHX/bTHXc/bTHXm (Ribosomal_bTHX/bTHXc/bTHXm)
Type: Family

This entry represents a lineage-specific bacterial ribosomal small subunit protein bTHX (previously THX), originally shown to exist in the genus Thermus . The protein is conserved for the first 26 amino acids, past which some members continue with additional sequence, often repetitive or low-complexity. This entry also includes 30S ribosomal proteins bTHXc/bTHXm from plant chloroplasts and mitochondria, which have additional N-terminal transit peptides .
Inositol 2-dehydrogenase (Myo_inos_IolG)
Type: Family

Members of this family are known or predicted inositol 2-dehydrogenase sequences co-clustered with other enzymes for catabolism of myo-inositol or closely related compounds. Inositol 2-dehydrogenase catalyses the first step in inositol catabolism, the oxidation of myo-inositol to 2-keto-myo-inositol (2KMI or 2-inosose) . Members of this family may vary somewhat in their ranges of acceptable substrates and some may act on analogues to myo-inositol rather than myo-inositol per se.
TyrR-like, helix-turn-helix domain (HTH_TyrR)
Type: Domain

This entry describes the C-terminal DNA-binding helix-turn-helix domain of several regulators of aromatic amino acid metabolism. Examples include TyrR in Escherichia coli and in Haemophilus influenzae, and PhhR in Pseudomonas putida . Most members of this family have a sigma-54 interaction domain . The TyrR protein of Escherichia coli can act both as a repressor and as an activator of transcription .
Quinoprotein relay system zinc metallohydrolase 2 (SoxH-rel_PQQ_2)
Type: Domain

This entry represent a domain found in a group of putative Zn metallohydrolases, which share homology with the sulfate metabolism associated protein SoxH, Bacillus cereus beta-lactamase II (see PDB:1bc2), and, more distantly, hydroxyacylglutathione hydrolase (glyoxalase II).

Proteins containing this domain occur in genomes with both PQQ biosynthesis and a PQQ-dependent (quinoprotein) dehydrogenase that has a motif of two consecutive Cys residues (

). The Cys-Cys motif is associated with electron transfer by specialised cytochromes such as c551. All these genomes also include a fusion protein (

) whose domains resemble SoxY and SoxZ from thiosulfate oxidation. A conserved Cys in this fusion protein aligns to the Cys residue in SoxY that carries sulfur cycle intermediates. In many genomes, the genes for PQQ biosynthesis enzymes, PQQ-dependent enzymes, their associated cytochromes, and protein in this entry are clustered. Note that one to three closely related Zn metallohydrolases may occur; this entry represents a specific clade among them. Some proteins in this entry have a short additional N-terminal domain with four conserved Cys residues.
5-Dehydro-2-deoxygluconokinase (Myo_inos_IolC)
Type: Family

Members of this family are encoded from the iolC gene of known or putative inositol catabolism operons. Members with characterised function are 5-dehydro-2-deoxygluconokinases , which catalyse the fifth step in degradation from myo-inositol or closely related compounds. Note that many members of this family are fusion proteins with an additional C-terminal domain of unknown function, described by

.
Quinoprotein dehydrogenase-associated SoxYZ-like carrier (Fuse-rel_SoxYZ)
Type: Family

Members of this family are fusion proteins, with the N-terminal region similar to the sulfur oxidation protein SoxY (

) and the C-terminal region similar to sulfur oxidation protein SoxZ (

). Members occur exclusively in species with PQQ-dependent enzymes that have a Cys-Cys motif (

) for electron transfer to c550 family cytochrome. By homology to the sulfur moiety-binding subunit SoxY, we predict the conserved Cys in the Gly-Gly-Cys motif binds some unknown adduct .
Processed acidic surface protein (Acidic_LPXTA)
Type: Family

Members of this family are acidic surface proteins with an N-terminal signal peptide and a variant C-terminal sortase recognition sequence, LPXTA rather than LPXTG. The N-terminal region past the signal peptide is repeated a second or third time in many members of this family. Members occur in Firmicutes, encoded next to a dedicated sortase related to SrtC that assembles pilins, suggesting that this protein serves a structural rather than enzymatic role. Processing by the neighbouring sortase may result in polymerisation as well as surface attachment.
Polyketide synthase-associated domain (PKS_assoc_dom)
Type: Domain

This entry describes a rare domain found as the N-terminal region of a number of dinoflagellate-specific proteins that resemble type I polyketide synthases .
Sulfite dehydrogenase SoxC (Sulfite_DH_SoxC)
Type: Family

Members of this family are the sulfite dehydrogenase SoxC. All members have a twin-arginine translocation (TAT) signal for secretion of proteins with bound cofactor across the plasma membrane .
Putative ABC transporter periplasmic binding protein PhnD-like (ABC_peri_PhnD-like)
Type: Family

This entry represent a group of putative ABC transporter periplasmic binding proteins that belong to a larger family that includes phosphate, phosphite, and phosphonate transporters. It includes Prochlorococcus PhnD1, which binds strongly to inorganic phosphite and has very weak affinities to methylphosphonate (MPn) and phosphate .
B12 lower ligand biosynthesis radical SAM protein BzaD-like (BzaD-like)
Type: Family

This entry represents a group of radical SAM proteins mainly found in Clostridia, including the BzaD, also known as Putative variant cofactor biosynthesis B12-binding domain/radical SAM domain protein 1 (BzaD) from Eubacterium limosum . Members of this protein family are one of two tandem B12-binding domain/radical SAM domain proteins that occur in a genome context with a pair of homologues to ThiC (phosphomethylpyrimidine synthase,

), an enzyme that performs a complex rearrangement involved in thiamin biosynthesis, and a putative CobT (nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase), an enzyme of cobalamin biosynthesis.
Small ribosomal subunit protein eS1, archaeal (Ribosomal_eS1_arc)
Type: Family

This entry represents the small ribosomal subunit protein eS1, previously known as previously known as S3Ae, from Archaea.

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 .
Cardiolipin synthase A (CL_synthase_A)
Type: Family

Most bacteria use an enzyme belonging to the phospholipase D family as cardiolipin synthase. In contrast, eukaryotes and most actinobacteria use a cardiolipin synthase of the CDP-alcohol phosphatidyltransferase family .

This entry represents the ClsA sub-subfamily of cardiolipin synthases that belong to the phospholipase D family. These proteins catalyse the reversible phosphatidyl group transfer from one phosphatidylglycerol molecule to another to form cardiolipin (diphosphatidylglycerol) and glycerol . Bacillus subtilis has three genes (clsA, ywjE and ywiE) for CL synthase; the main role in CL synthesis being played by clsA .
Endonuclease III-like protein 1 (NTH1)
Type: Family

This entry includes human endonuclease III-like protein 1 (NTH1) and its homologues from animals, yeasts and plants. NTH1 is a bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyses the first step in base excision repair (BER), the primary pathway for the repair of oxidative DNA damage . In budding yeasts it is also known as Ntg1, which has an a paralogue, Ntg2 . Yeast Ntg1 creates a double-strand break at mtDNA origins that stimulates replication in response to oxidative stress .
Transcription termination/antitermination protein NusA, bacterial (NusA_bac)
Type: Family

NusA, or N utilisation substance protein A, is a multidomain regulator of transcript elongation in bacteria and archaea. This entry represents bacterial NusA, which interacts with elongating complexes and the nascent RNA transcript in ways that stimulate pausing and termination, but that can be switched to antipausing and antitermination by other accessory proteins . It is also involved in both DNA repair and damage tolerance pathways .
PAN2-PAN3 deadenylation complex catalytic subunit PAN2 (PAN2)
Type: Family

Pan2 is a catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of the two eukaryotic poly(A) nuclease complexes (Ccr4-Caf1 and Pan2-Pan3) involved in mRNA decay . Pan2 is involved in the initial stage of deadenylation of mRNA, which is required for poly(A) tail shortening .

Regulation of mRNA decay rates in eukaryotic cells affects gene expression . The Pan2-Pan3 complex shortens cytoplasmic mRNA 3' polyA tails to regulate mRNA stability . In the complex Pan2 provides the catalytic activity, whereas Pan3 mediates Pan2 recruitment to mRNA targets .
PAN2-PAN3 deadenylation complex subunit PAN3 (PAN3)
Type: Family

Pan3 is a regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of the two eukaryotic poly(A) nuclease complexes (Ccr4-Caf1 and Pan2-Pan3) involved in mRNA decay . It contains a PABP-interacting motif 2 (PAM2) that binds to the C-terminal domain of polyA binding proteins (PABPs) . It recruits the Pan2-Pan3 complex to mRNA through the Pan3-PABP interaction .

Regulation of mRNA decay rates in eukaryotic cells affects gene expression . The Pan2-Pan3 complex shortens cytoplasmic mRNA 3' polyA tails to regulate mRNA stability . In the complex Pan2 provides the catalytic activity, whereas Pan3 mediates Pan2 recruitment to mRNA targets .
Regulator of telomere elongation helicase 1 (RTEL1)
Type: Family

Regulator of telomere elongation helicase 1 (Rtel1) is the animal functional analogue of yeast Srs2, which is a DNA helicase and DNA-dependent ATPase involved in DNA repair and checkpoint recovery . Rtel1 is an essential DNA helicase that disassembles a variety of DNA secondary structures to facilitate DNA replication, repair, and recombination processes, and to maintain both telomeric and genomic stability . It is recruited by Trf2 to telomeres in S phase to promote T-Loop unwinding . It is also required for the export and the correct cytoplasmic trafficking of the small nuclear (sn) RNA pre-U2, a component of the major spliceosome complex . Human Rtel1 is implicated in the etiology of Dyskeratosis congenital (DC, is an inherited bone marrow failure and cancer predisposition syndrome) . Point mutations in its helicase domains, and truncations which result in loss of its C terminus have been discovered in DC families. It acts as anti-recombinase and antagonises homologous recombination by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis . Rtel1 is also a candidate gene influencing glioma susceptibility .
DNA primase DnaG, bacteria (DnaG_bac)
Type: Family

DNA primase DnaG catalyses the synthesis of short RNA molecules used as primers for the DNA polymerase during DNA replication . The DNA primases of bacteria and bacteriophages are classified into one group, whereas the primases of eukaryotes and archaea belong to a second group. Bacterial primase DnaG works together with replicative helicase, DnaB, to unwind the DNA template and initiate thousands of regularly-spaced Okazaki fragments to promote fork progression in the lagging strand .
Mitochondrial glycine transporter Hem25/SLC25A38 (Hem25/SLC25A38)
Type: Family

This entry includes a group of mitochondrial glycine transporters, including Hem25 from budding yeasts and SLC25A38 from humans. They transport glycine into mitochondria for initiation of heme biosynthesis .

Solute carrier family 25 member 38 (SLC25A38) belongs to the SLC25 family, whose members are inner mitochondrial membrane transporters promoting the exchange of one metabolite for another across the inner mitochondrial membrane. Mutations in the SLC25A38 gene cause nonsyndromic autosomal recessive congenital sideroblastic anemia .
Elongation factor G, chloroplastic (EF_G_plantC)
Type: Family

Bacterial translation elongation factor G (EF-G) catalyses translocation during peptide elongation and mediates ribosomal disassembly during ribosome recycling with the aid of the ribosomal recycling factor (RRF). This entry represents plant plastid EF-G (also known as SCO1), which displays a 59% homology to prokaryotic EF-G proteins. It is a chloroplast-localised elongation factor involved in protein synthesis in plastids. In Arabidopsis, the mutations in sco1 affect the chloroplast mRNA translation that does not only influence chlorophyll accumulation during chloroplast formation in cotyledons, but also other developmental processes such as germination and flowering .
Ubiquitin carboxyl-terminal hydrolase 16 (UBP16)
Type: Family

Ubiquitin carboxyl-terminal hydrolase 16 (UBP16 or Ubp-M), also known as ubiquitin-specific protease 16 (USP16), is a histone H2A deubiquitinase required for cell cycle M phase progression. It also regulates gene expression in G1/S phase. In Xenopus embryos, it regulates embryonic anterior-posterior patterning through the regulation of Hox gene expression . USP16 is a critical regulator of DNA damage response that fine-tunes DNA damage-induced histone ubiquitin foci formation .
Exosome complex component Csl4, archaea (Exosome_Csl4_arc)
Type: Family

Csl4 is a non-catalytic component of the exosome, a complex involved in RNA processing and degradation . he exosome consists of Rrp4, Rrp41, Rrp42 and Csl4. The subunits Rrp41 and Rrp42 form a phosphorolytically active hexamer, with an RNA-binding cap on the top consisting of a homotrimer of either Rrp4 or Csl4. The presence of different proteins in the cap may enable interactions with different substrates. It has been shown that the archaeal DnaG protein needs Csl4 for binding to the exosome. DnaG is a poly(A)-binding protein and enhances the degradation of adenine-rich transcripts by the Csl4-exosome .
Ribosome-releasing factor 2, mitochondrial (EFG2)
Type: Family

Bacterial translation elongation factor G (EF-G) catalyses translocation during peptide elongation and mediates ribosomal disassembly during ribosome recycling with the aid of the ribosomal recycling factor (RRF). Human mitochondria contains two EF-G homologues, EF-G1 and EF-G2. This entry represents EF-G2, also known as ribosome-releasing factor 2 (RRF2), which mediates ribosome recycling with human mitochondrial RRF, but lacks translocation activity . This entry also includes EFG2 homologues from other animals and fungi. Its budding yeast homologue, known as Mef2, is required for respiratory growth and is essential for mitochondrial genome maintenance .
Outer membrane lipoprotein RcsF (RcsF)
Type: Family

The Rcs signalling system consists of the RcsCDB phosphorelay signalling pathway and two proteins that modulate the activity of the system, RcsA and RcsF. The Rcs system regulates pathways involved in maintenance of cell wall integrity, cell division, motility, and virulence. RcsF is a outer membrane (OM) lipoprotein that mediates the signalling to the sensor RcsC . RcsF functions to sense defects such as changes in lipopolysaccharide .