SII-SWORD/CoKE huggingface dataset:
Der GTPase-activating protein YihI (YihI)
Type: Family

This entry represents Der GTPase-activating protein YihI from Escherichia coli (strain K12) and similar proteins predominantly found in Gammaproteobacteria. YihI is a GTPase activating protein (GAP) that modifies the activity of Der, a 50S ribosomal subunit stability factor. The stimulation is specific to Der as YihI does not stimulate the GTPase activity of Era or ObgE. The interaction of YihI with Der requires only the C-terminal 78 amino acids of YihI . A yihI deletion mutant is viable and shows a shorter lag period, but the same post-lag growth rate as a wild-type strain. yihI is expressed during the lag period. Overexpression of yihI inhibits cell growth and biogenesis of the 50S ribosomal subunit . YihI is an unusual, highly hydrophilic protein with an uneven distribution of charged residues, resulting in an N-terminal region with high pI and a C-terminal region with low pI .
RelB antitoxin/Antitoxin DinJ (RelB/DinJ)
Type: Family

Plasmids may be maintained stably in bacterial populations through the action of addiction modules, in which a toxin and antidote are encoded in a cassette on the plasmid. In any daughter cell that lacks the plasmid, the toxin persists and is lethal after the antidote protein is depleted. Toxin/antitoxin pairs are also found on main chromosomes, and likely represent selfish DNA. Sequences in the seed for this alignment all were found adjacent to toxin genes. Several toxin/antitoxin pairs may occur in a single species. RelE and RelB form a toxin-antitoxin system; RelE cleaves mRNA during translation on the ribosome . RelB binds and inhibits RelE and it regulates transcription by operator binding and conditional cooperativity controlled by RelE. RelE and RelB form a V-shaped heterotetrameric complex which has a ribbon-helix-helix (RHH) dimerization domain at the apex. .

DinJ is an antitoxin component of a toxin-antitoxin (TA) module. It is a labile antitoxin that counteracts the effect of the YafQ toxin . It forms a heterotetrameric complex with YafQ and the structure of this complex revealed that the N-terminal region of DinJ folds into a ribbon-helix-helix motif that dimerises for DNA recognition, and the C-terminal portion of each DinJ wraps around a YafQ molecule . Together, they they bind their own promoter, and by analogy to other TA modules probably repress its expression. Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation .
Protein of unknown function DUF416 (DUF416)
Type: Family

This is a bacterial family of uncharacterised proteins.
Inner membrane protein RclC-like (RclC-like)
Type: Family

This family of uncharacterised proteins appears to be restricted to proteobacteria. It includes inner membrane protein RclC (YkgD) from
Escherichia coli
, which is a reactive chlorine-specific transcription factor . These proteins are related to the DoxX family

. Members of this family form a confident homodimeric structure, for example UniProtKB:A0A4R5FQM0 iPTM=0.94.
Opacity-associated protein A, LysM-like domain (LysM_Opacity-associatedA)
Type: Domain

The OapA domain gets its name from the Haemophilus influenzae protein OapA, which is required for the expression of colony opacity, thus opacity- associated protein A . The OapA protein is required for efficient nasopharyngeal mucosal colonization, and its expression is associated with a distinctive transparent colony phenotype. OapA is thought to be a secreted protein, and its expression exhibits high-frequency phase variation . The OapA protein contains a C-terminal OapA domain, which in the E. coli protein YtfB has been shown to bind to peptidoglycan . A screen to identify factors that affect cell division in E. coli discovered that overproducing a fragment of YtfB, including its OapA domain, caused cells to grow as long filaments . OapA domains are commonly associated with other domains that are involved in breaking peptidoglycan cross-links such as

. The OapA domain is distantly related to

another peptidoglycan binding domain.

This domain is also found in the cell wall peptidoglycan (PG) DD-endopeptidases ShyA and ShyB essential for cell growth and elongation .
Transglycosylase-associated protein (Transgly_assoc)
Type: Family

This bacterial protein is predicted to be an integral membrane protein. Some family members have been annotated as transglycosylase-associated proteins, but no experimental evidence is provided. This family was annotated based on the information in

.
Pseudouridine-5'-phosphate glycosidase (PsuG)
Type: Family

Members of this entry catalyse the hydrolysis of pseudouridine 5'-phosphate (PsiMP) to ribose 5-phosphate and uracil .

It is also reported to be involved in the synthesis of indigoidine, which is a blue pigment synthesised by Erwinia chrysanthemi implicated in pathogenicity and protection from oxidative stress. IdgA is involved in indigoidine biosynthesis, but its specific function is unknown .
Uncharacterised protein family, zinc metallopeptidase putative (Uncharacterised_pept_Zn_put)
Type: Family

Members of this family of bacterial proteins are described as hypothetical proteins or zinc metallopeptidases. The majority have a HExxH zinc-binding motif characteristic of neutral zinc metallopeptidases, however there is no evidence to support their function as metallopeptidases.
GrpB/Dephospho-CoA kinase (GrpB/CoaE)
Type: Family

This family has been suggested to belong to the nucleotidyltransferase superfamily . It occurs at the C terminus of dephospho-CoA kinase (CoaE) in a number of cases, where it plays a role in the proper folding of the enzyme .
Polysaccharide pyruvyl transferase (Polysacch_pyruvyl_Trfase)
Type: Domain

Pyruvyl-transferases are involved in peptidoglycan-associated polymer biosynthesis. CsaB in Bacillus anthracis is necessary for the non-covalent anchoring of proteins containing an SLH (S-layer homology) domain to peptidoglycan-associated pyruvylated polysaccharides. WcaK and AmsJ are involved in the biosynthesis of colanic acid in Escherichia coli and of amylovoran in Erwinia amylovora .
Endonuclease I (Endonuclease-I)
Type: Family

Bacterial periplasmic or secreted (

) Escherichia coli endonuclease I (EndoI) is a sequence independent endonuclease located in the periplasm. It is inhibited by different RNA species. It is thought to normally generate double strand breaks in DNA, except in the presence of high salt concentrations and RNA, when it generates single strand breaks in DNA. Its biological role is unknown . Other family members are known to be extracellular . This family also includes a non-specific, Mg
2+
-activated ribonuclease precursor (

) .
Sporulation stage V, protein S (SpoVS)
Type: Family

In Bacillus subtilis this protein interferes with sporulation at an early stage and this inhibitory effect is overcome by SpoIIB and SpoVG. SpoVS seems to play a positive role in allowing progression beyond stage V of sporulation. Null mutations in the spoVS gene block sporulation at stage V, impairing the development of heat resistance and coat assembly .
CopC domain (CopC_dom)
Type: Domain

Copper resistance protein C (CopC) is a bacterial blue copper protein that binds 1 atom of copper per protein molecule. Along with CopA, CopC mediates copper resistance by sequestration of copper in the periplasm .

The structure of CopC consists of a Greek key β-barrel fold .
Domain of unknown function DUF418 (DUF418)
Type: Domain

This domain of unknown function is found in probable integral membrane proteins.
Transposase, Tc5, C-terminal (Transposase_Tc5_C)
Type: Domain

This domain corresponds to a C-terminal cysteine rich region that probably binds to a metal ion and could be DNA-binding. It is found in association with the DDE superfamily domain (

).
Uncharacterised protein YjbR (YjbR)
Type: Family

YjbR is predicted to contain the DNA binding domain comprising the 'double wing' motif .
Protein of unknown function DUF420 (DUF420)
Type: Family

This is a predicted membrane protein with four transmembrane helices.
YetF, C-terminal domain (DUF421)
Type: Domain

This domain is found at the C-terminal end of the YetF protein, which contains three N-terminal transmembrane helices.
Bisanhydrobacterioruberin hydratase CruF-like (CruF-like)
Type: Family

This family consists of bacterial and archaeal proteins. The representative member is CruF, a C50 carotenoid 2',3'-hydratase involved in the synthesis of the C50 carotenoid bacterioruberin in the halophilic archaeon Haloarcula japonica .
Protein of unknown function DUF424 (DUF424)
Type: Family

Members of this family of uncharacterised proteins are found in bacteria and archaea.
tRNA (guanine(9)-N1)-methyltransferase, eukaryotic (tRNA_m1G_MeTrfase_euk)
Type: Family

In transfer RNA many different modified nucleosides are found, especially in the anticodon region.
tRNA (guanine-N1-)-methyltransferase

is one of several nucleases operating together with the tRNA-modifying enzymes before the formation of the mature tRNA. It catalyses the reaction:

S-adenosyl-L-methionine + tRNA ->S-adenosyl-L-homocysteine + tRNA containing N1-methylguanine

Methylating guanosine(G) to N1-methylguanine (1-methylguanosine (m1G)) at position 37 of tRNAs that read CUN (leucine), CCN(proline), and CGG (arginine) codons. The presence of m1G improves the cellular growth rate and the polypeptide steptime and also prevents the tRNA from shifting the reading frame .

The mechanism of the trmD3-induced frameshift involving mutant tRNA(Pro) and tRNA(Leu) species has been investigated . It has been suggested that the conformation of the anticodon loop may be a major determining element for the formation of m1G37 in vivo .
Photolyase PhrB-like (PhrB-like)
Type: Family

This entry includes PhrB from Agrobacterium fabrum and related proteins. PhrB is a photolyase involved in the repair of UV-induced (6-4) lesions in DNA. It catalyzes the photoreactivation of (6-4) pyrimidine-pyrimidone photoproducts by using blue-light energy .
Nucleoid-associated protein NdpA (Nucleoid_associated_NdpA)
Type: Family

The Escherichia coli nucleoid contains DNA in a condensed but functional form. Analysis of proteins released from isolated spermidine nucleoids after treatment with DNase I revealed significant amounts of two proteins not previously detected in wild-type E. coli. Partial amino-terminal sequencing has identified them as the products of rdgC and yejK. These proteins are strongly conserved in Gram-negative bacteria, suggesting that they have important cellular roles .

This entry represents the product of gene yejK, nucleoid associated protein NdpA.
Positive regulator of sigma(E), RseC/MucC (SigmaE_reg_RseC_MucC)
Type: Family

This bacterial family of integral membrane proteins represents a positive regulator of the sigma(E) transcription factor, namely RseC/MucC. The sigma(E) transcription factor is up-regulated by cell envelope protein misfolding, and regulates the expression of genes that are collectively termed ECF (devoted to Extra-Cellular Functions) . In Pseudomonas aeruginosa, derepression of sigma(E) is associated with the alginate-overproducing phenotype characteristic of chronic respiratory tract colonization in cystic fibrosis patients. The mechanism by which RseC/MucC positively regulates the sigma(E) transcription factor is unknown. RseC is also thought to have a role in thiamine biosynthesis in Salmonella typhimurium . In addition, this family also includes an N-terminal part of RnfF, a Rhodobacter capsulatus protein, of unknown function, that is essential for nitrogen fixation. This protein also contains a domain found in ApbE protein

.
Invasion gene expression up-regulator, SirB (SirB)
Type: Family

SirB up-regulates Salmonella typhimurium invasion gene transcription. It is, however, not essential for the expression of these genes. Its function is unknown .
Domain of unknown function DUF427 (DUF427)
Type: Domain

This domain consists of 10 β-strands and 2 short α-helices forming a β-tent fold .
Protein of unknown function DUF429 (DUF429)
Type: Family

This is a family of uncharacterised proteins.
Protein arginine N-methyltransferase SFM1-like (SFM1-like)
Type: Family

This entry includes Protein arginine N-methyltransferase SFM1 from Saccharomyces cerevisiae and similar proteins from fungi and archaea. Sfm1 is a S-adenosyl-L-methionine-dependent protein-arginine N-methyltransferase that monomethylates ribosomal protein S3 (RPS3) at 'Arg-146' .
Transferrin receptor-like, dimerisation domain (TFR-like_dimer_dom)
Type: Domain

This entry represents the dimerisation domain found in the transferrin receptor, as well as in a number of other proteins including glutamate carboxypeptidase II and N-acetylated-alpha-linked acidic dipeptidase like protein.

The transferrin receptor (TfR) assists iron uptake into vertebrate cells through a cycle of endo- and exocytosis of the iron transport protein transferrin (Tf). TfR binds iron-loaded (diferric) Tf at the cell surface and carries it to the endosome, where the iron dissociates from Tf. The apo-Tf remains bound to TfR until it reaches the cell surface, where apo-Tf is replaced by diferric Tf from the serum to begin the cycle again. Human TfR is a homodimeric type II transmembrane protein. The crystal structure of a TfR monomer reveals a 3-domain structure: a protease-like domain that closely resembles carboxy- and amino-peptidases; an apical domain consisting of a β-sandwich; and a helical dimerisation domain. The dimerisation domain consists of a 4-helical bundle that makes contact with each of the three domains in the dimer partner .
Protein of unknown function DUF432 (DUF432)
Type: Family

This is an archaeal protein of unknown function.
Protein of unknown function DUF433 (DUF433)
Type: Family

This entry includes a group of uncharacterised proteins, including VapB45 from Mycobacterium tuberculosis. VapB45 is possibly the antitoxin component of a type II toxin-antitoxin (TA) module. Its cognate toxin is VapC45 .
Domain of unknown function DUF434 (DUF434)
Type: Domain

The function of DUF434 is not known.
Glutamate--cysteine ligase (Glu_cys_ligase)
Type: Domain

This is a group of bacterial glutamate-cysteine ligases that carry out the first step of the glutathione biosynthesis pathway according to the following equation:
ATP + L-glutamate + L-cysteine = ADP + phosphate + L-glutamyl-L-cysteine
(L-aminohexanoate can replace glutamate).
Thiamin pyrophosphokinase, catalytic domain (TPK_catalytic)
Type: Domain

Thiamin pyrophosphokinase (TPK,

) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. The structure of thiamin pyrophosphokinase suggests that the enzyme may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis .
Lipid/polyisoprenoid-binding, YceI-like (Lipid/polyisoprenoid-bd_YceI)
Type: Domain

This entry represents the lipid-binding protein YceI from Escherichia coli and the polyisoprenoid-binding protein TTHA0802 from Thermus thermophilus . Both these proteins share a common domain with an 8-stranded β-barrel fold, which resembles the lipocalin fold, although no sequence homology exists with lipocalins. In TTHA0802, the protein binds the polyisoprenoid chain within the pore of the barrel via hydrophobic interactions . Sequence homologues of this core structure are present in a wide range of bacteria and archaea. The crystal structures of Yce1 and TTHA0802 suggest that this family of proteins plays an important role in isoprenoid quinone metabolism and/or transport and/or storage .
Thiamin pyrophosphokinase, thiamin-binding domain (Thiamin_PyroPKinase_B1-bd)
Type: Domain

Thiamin pyrophosphokinase (TPK,

) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. The structure of thiamin pyrophosphokinase suggest that the enzyme may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis .
ASCH domain (ASCH_domain)
Type: Domain

The ASCH domain adopts a β-barrel fold similar to that of the PUA domain (

). It is thought to function as an RNA-binding domain during coactivation, RNA-processing and possibly during prokaryotic translation regulation .
Sarcosine oxidase, gamma subunit (SoxG)
Type: Family

Sarcosine oxidase is a hetero-tetrameric enzyme that contains both covalently bound FMN and non-covalently bound FAD and NAD
+
. This enzyme catalyzes the oxidative demethylation of sarcosine to yield glycine, H
2
O
2
, and 5,10-CH2-tetrahydrofolate (H4folate) in a reaction requiring H4folate and O
2
.
dsDNA mimic, putative (dsDNA_mimic_put)
Type: Family

This entry represents hypothetical proteins such as HI1450, which is believed to act as a putative dsDNA mimic. HI1450 is an acidic protein with a core structure consisting of α(2)-β(4), where the α-helices are packed against the side of an anti-parallel 4-stranded β meander. As such, it has some similarity to the dsDNA mimics uracil-DNA glycosylase inhibitor and nuclease A inhibitor (NuiA), including the distribution of surface charges and the position of the hydrophobic cavity . DNA mimics act to inhibit or regulate dsDNA-binding proteins.
Tic22-like (Tic22-like)
Type: Family

Chloroplast function requires the import of nuclear encoded proteins from the cytoplasm across the chloroplast double membrane. This is accompished by two protein complexes, the Toc complex located at the outer membrane and the Tic complex loacted at the inner membrane . The Toc complex recognises specific proteins by a cleavable N-terminal sequence and is primarily responsible for translocation through the outer membrane, while the Tic complex translocates the protein through the inner membrane.

This entry represents Tic22, a core member of the Tic complex. Tic22 is a soluble protein and the only Tic complex component of the intermembrane space that has been shown to interact with preproteins during import. It may also act as a chaperone that prevent misfolding or missorting of the preprotein to the intermembrane space and potentially serve as a component that links the Toc and Tic complexes .
Tim44-like domain (Tim44-like_dom)
Type: Domain

Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane . Tim44 is thought to bind phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region . This entry represents the C-terminal region of Tim44 that has been shown to form a stable proteolytic fragment in yeast. This region is also found in a set of smaller bacterial proteins. The molecular function of the bacterial members is unknown, but transport seems likely. The crystal structure of the C terminus of Tim44 has revealed a large hydrophobic pocket which might play an important role in interacting with the acyl chains of lipid molecules in the mitochondrial membrane .
Domain of unknown function DUF438 (DUF438)
Type: Domain

This is a a group of uncharacterised proteins.
Taxis protein CheF1/F2 (CheF1/F2)
Type: Family

This protein family represents Taxis protein CheF1/F2 from Halobacterium salinarum and similar proteins found in archaea. CheF1/2 are archaea-specific adaptor proteins that link the bacterial-like chemotaxis signal transduction system to the archaeal motility machinery .

CheF1 interact with the chemotaxis proteins CheY, CheD and CheC2 as well as the flagella-accessory proteins FlaCE and FlaD, and is essential for any tactic response. This protein is conserved in almost all chemotactic archaea.

CheF2 is found in a very limited set of haloarchaea and is thought to have a less important role in chemotaxis .
Uncharacterised protein family UPF0756, transmembrame (UPF0756_TM)
Type: Family

This entry contains proteins of unknown function. They are predicted to be transmembrane proteins with 4 TM domains.
Protein of unknown function DUF445 (DUF445)
Type: Family

This entry represents a large family of proteins with unknown function. They are predicted to be transmembrane (TM) proteins with 2 or 3 TM domains.
Protein of unknown function UCP006257 (UCP006257)
Type: Family

This family of uncharacterised conserved proteins includes YqcC from Escherichia coli.
Prokaryotic chromosome segregation/condensation protein MukE (Scp_MukE)
Type: Family

MukE is involved in the segregation and condensation of prokaryotic chromosomes. MukE along with MukF (

) interact with MukB (

) in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli . The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC . ScpA (

) and ScpB (

) have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.
DUF447, N-terminal domain (DUF447_N)
Type: Domain

This entry represents a domain found N-terminal in archaeal and bacterial proteins of unknown function. It adopts an FMN-binding split β-barrel structure and binds to flavin mononucleotide (FMN)

. This domain is found N-terminal to

.
TRAP transporter, small membrane protein DctQ (TRAP_DctQ)
Type: Family

The tripartite ATP-independent periplasmic (TRAP) transporters are substrate-binding protein (SBP)-dependent secondary transporters ubiquitous in prokaryotes, but absent from eukaryotes. They are comprised of an SBP of the DctP or TAXI families and two integral membrane proteins of unequal sizes that form the DctQ and DctM protein families (the small and large membrane components respectively). The TRAP transporter for sialic acid consists of the SBP siaP, and siaQM (termed siaT in some cases), encoding the fused integral membrane protein .

This family consists of DctQ homologues found in TRAP transporters .
Sporulation stage V, protein R (Spore_V_R)
Type: Family

One of the family members

is Bacillus subtilis stage V sporulation protein R, which is involved in spore cortex formation .

Stage V sporulation protein R is involved in spore cortex formation . Little is known about cortex biosynthesis, except that it depends on several sigma E controlled genes, including spoVR . YcgB has been suggested to be part of a conserved signalling pathway with YeaH and YeaG. This pathway may be involved in nitrogen metabolism (see Supplementary note 5 in )
Vancomycin resistance VanW (Vancomycin_resist_VanW)
Type: Family

Members of this family include vancomycin resistance protein W (VanW). Genes encoding members of this family have been found in vancomycin resistance gene clusters vanB and vanG . The function of VanW is unknown.
D-galactarate/Altronate dehydratase, second domain (GD_AH_second)
Type: Domain

This entry represents the middle domain of D-galactarate dehydratase (GarD,

) and altronate dehydratase (

) . When purified, both enzymes are catalytically inactive in the absence of added Fe
2+
, Mn
2+
, and beta-mercaptoethanol. Synergistic activation of altronate hydrolase activity is seen in the presence of both iron and manganese ions, suggesting that the enzyme may have two ion binding sites. Mn
2+
appears to be part of the enzyme active centre, but the function of the single bound Fe
2+
ion is unknown. The hydratase has no Fe-S core . In the crystal structure, GarD forms dimers, each monomer consisting of three domains: the N-terminal β-clip SAF domain connected by a long linker to the second domain which contains three parallel β-strands surrounded by three α-helices and that serves as a dimerisation interface between monomers, and a C-terminal α/β domain with a novel topology resembling a Rossmann fold, with an unusual helix crossover . This entry represents the second domain and it interacts with the C-terminal domain from the second chain to form a dimerisation surface .

This domain is also found in (2R)-sulfolactate sulfo-lyase subunit beta (suyB) (

) from Chromohalobacter salexigens .