SII-SWORD/CoKE huggingface dataset:
D-xylose-proton symporter-like (XylE-like)
Type: Family

This entry includes bacterial transporters such as D-xylose-proton symporter (XylE or XylT), arabinose-proton symporter (AraE), galactose-proton symporter (GalP), major myo-inositol transporter IolT, glucose transport protein, putative metabolite transport proteins YfiG, YncC, and YwtG, and similar proteins

,

,

,

]. The symporters XylE, AraE, and GalP facilitate the uptake of D-xylose, arabinose, and galactose, respectively, across the boundary membrane with the concomitant transport of protons into the cell. IolT is involved in polyol metabolism and myo-inositol degradation into acetyl-CoA. The XylE-like subfamily belongs to the Glucose transporter-like (GLUT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins
StbB-like (StbB-like)
Type: Family

This entry represents a group of uncharacterised proteins found mainly in gamma- and betaproteobacteria. They are homologues of StbB that is part of an atypical plasmid stabilisation system. The latter is composed of two proteins, StbA and StbB, which act to balance plasmid physiology. StbA is essential to ensure faithful assortment of plasmid copies to daughter cells, whereas StbB is required for plasmid adequate localisation for conjugation .
E3 ubiquitin-protein ligase RNF182, RING finger, HC subclass (RNF182_RING-HC)
Type: Domain

This entry represents the C3HC4-type RING-HC finger of RNF182.
RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway , suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. It also plays a role in the inhibition of TLR-triggered innate immune response by mediating 'Lys'-48-linked ubiquitination and subsequent degradation of NF-kappa-B component RELA . RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.
Terminase, large subunit-like, virus (Gp19-like_virus)
Type: Family

This entry represents a group of proteins from tailed bacteriophages and bacterial prophages, including Terminase, large subunit from from Enterobacteria phage T3 and T7 (Gp19). This protein acts as an ATP driven molecular motor, necessary for viral DNA translocation into empty capsids, and as an endonuclease that cuts the viral genome at a unique and precise dsDNA sequence to initiate and to end a packaging reaction .

Many DNA viruses package their genomes in a reaction catalysed by a powerful DNA-packaging motor, a complex that consists of a dodecameric portal protein and a terminase that converts ATP hydrolysis into linear translation of DNA. The terminase is formed by a small subunit, which binds to packaging initiation sites to prepare for genome packaging, and a large subunit which has ATPase activity and binds directly to the portal protein. The small subunit is essential for binding to DNA and also activates the large subunit ATPase activity .
Small ribosomal subunit protein uS7m, fungi (Ribosomal_uS7m_fungi)
Type: Domain

The small ribosomal subunit protein uS7, also known as Ribosomal protein (RP)S7, is an important part of the translation process which is universally present in the small subunit of prokaryotic and eukaryotic ribosomes . Fungal and plants mitochondrial uS7 shows less homology to the mammalian than to bacterial uS7. The small subunits of bacteria and eukaryotes have the same shape of head, body, platform, beak, and shoulder . uS7 is located at the head of the small subunit and is a primary ribosomal RNA (rRNA) binding protein that assists in rRNA folding and the binding of other proteins during small subunit assembly in all species. uS7 is also involved in the formation of the mRNA exit channel at the interface of the large and small subunits.

This entry represents the structural domain of fungal uS7 .
Zinc finger and BTB domain-containing protein 39, BTB/POZ domain (ZBTB39_BTB_POZ)
Type: Domain

This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in human Zinc finger and BTB domain-containing protein 39 (ZBTB39) and similar proteins from vertebrates. ZBTB39 may be involved in transcriptional regulation. Its specific function is as yet unknown. It contains a BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids .
DLW-39-like (DLW39-like)
Type: Family

This entry represents a group of proteins specific to actinomycetes that are related to the small protein DLW-39. These proteins contain a highly hydrophobic stretch of about 15 amino acids, flanked by pairs of basic residues, and a C-terminal region, in which most members of the family share the motif (DLW). Members of this family are typically about 39 amino acids in length. This family is uncharacterised.
Tubulin-specific chaperone cofactor E-like protein, ubiquitin-like domain (TBCEL_Ubl)
Type: Domain

This entry represents a ubiquitin-like domain present in Tubulin-specific chaperone cofactor E-like protein (TBCEL) and similar animal proteins. TBCEL, also termed leucine-rich repeat-containing protein 35 (LRRC35), or E-like (EL), is a regulator of tubulin stability, suggesting a link between tubulin turnover and vesicle transport. TBCEL is abundantly expressed in testis, but is also present in several tissues at a much lower level. It is required for the synchronous movement of the investment cones and is important for normal male fertility. This protein shows high sequence similarity to tubulin-specific chaperone cofactor E (TBCE), a component of the multimolecular complex required for tubulin heterodimer formation in all eukaryotic cells. It contains a leucine-rich repeat protein-protein interaction domain and a C-terminal ubiquitin-like (Ubl) domain, but does not harbour the cytoskeleton-associated protein with glycine-rich segment (CAP-Gly) domain found in TBCE .
BREX system phosphatase PglZ (BREX_PglZ)
Type: Family

This entry includes PglZ, an alkaline phosphatase-like protein associated with BREX (bacteriophage exclusion) type 1 systems . This system provides immunity against bacteriophage, it allows phage adsorption but blocks phage DNA replication. PglZ is predicted to have a phosphatase activity and is described as probable antitoxin component of a type II toxin-antitoxin (TA) system, that inhibits the toxic activity of its cognate toxin PglX . PglZ is one of the four genes (pglW, pglX, pglY, and pglZ) that were shown to be necessary and sufficient for the Pgl phenotype .
LysR-type transcriptional regulator TdcA/AbgR, PBP2 domain (TdcA/AbgR_PBP2)
Type: Domain

TdcA, a member of the LysR family, activates the expression of the anaerobically-regulated tdcABCDEFG operon which is involved in the degradation of L-serine and L-threonine to acetate and propionate, respectively. The tdc operon is comprised of one regulatory gene tdcA and six structural genes, tdcB to tdcG. The expression of the tdc operon is affected by several transcription factors including the cAMP receptor protein (CRP), integration host factor (IHF), histone-like protein (HU), and the operon specific regulators TdcA and TcdR .

This entry represents a substrate-binding domain that shows significant homology to the type 2 periplasmic binding proteins (PBP2), which are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap . After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis . This entry also includes the transcriptional regulator AbgR from E.coli.
Sensor histidine kinase ArsS-like (ArsS-like)
Type: Family

This entry represents a group of proteins from epsilonproteobacteria, including Sensor histidine kinase ArsS from Helicobacter pylori. ArsS is a sensor histidine kinase participating in a two-component system that controls the response to acid conditions encountered during the process of gastric colonisation and genes involved in biofilm formation and acid adaptation by acting on major ammonia-producing pathways .
Choice-of-anchor K domain (Choice_anch_K)
Type: Domain

The choice-of-anchor K is a rather uncommon extracellular domain of about 170 amino acid residues long. Several proteins containing this domain have C-terminal regions that target them for sorting to the cell surface, including PEP-CTERM (

) and its variant VPLPA-CTERM (

). The domain is found occasionally in RTX toxin-like proteins.
RCC1 and BTB domain-containing protein 1, BTB/POZ domain (RCBTB1_BTB_POZ)
Type: Domain

This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in human RCC1 and BTB domain-containing protein 1 (RCBTB1) and similar sequences from vertebrates. RCBTB1 is also called chronic lymphocytic leukemia deletion region gene 7 protein (CLLD7), CLL deletion region gene 7 protein, regulator of chromosome condensation and BTB domain-containing protein 1, or E4.5. It is a novel chromosome condensation regulator-like guanine nucleotide exchange factor that may be involved in cell cycle regulation by chromatin remodelling. It may also function as a tumour suppressor that regulates pathways of DNA damage/repair and apoptosis. RCBTB1 may also be a substrate adaptor for a cullin3 (CUL3) E3 ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Biallelic mutations in RCBTB1 may cause isolated and syndromic retinal dystrophy. It contains an RCC1 repeat, a BTB domain, and a BACK domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids .
Inner membrane protein YejM, enterobacterales (YejM_enterobact)
Type: Family

This entry represents a group of proteins from enterobacterales, including Inner membrane protein YejM from Escherichia coli (

). YejM (also known as LapC, PbgA) belongs to a regulatory system that controls the activity of LpxC, the enzyme that catalyses the first committed step in the LPS synthesis .

The YejM(PbgA) structure was shown to contain five N-terminal transmembrane helices upon which the C-terminal periplasmic domain sits and an interfacial domain made of three-helical bundle that connects them .
Small protein MgtS (MgtS)
Type: Family

This entry includes Small protein MgtS from Escherichia coli (previously known as YneM), and similar short sequences from enterobacterales. MgtS, the product of a small open reading frame (smORF), is a small inner membrane protein that modulates Mg2 concentrations through its effects on the P-type transporter MgtA. MgtS is induced by very low concentrations of Mg2 in a PhoPQ-dependent manner and acts by binding and stabilising MgtA to increase the intracellular Mg2 levels and maintain cell integrity upon Mg2 depletion . It forms a single transmembrane helix .
Deaminated glutathione amidase (De_GSH_amidase)
Type: Family

This entry represents a group of proteins predominantly found in proteobacteria, including deaminated glutathione amidase from Escherichia coli (YbeM), an enzyme that hydrolyses deaminated glutathione (dGSH) to 2-oxoglutarate and L-cysteinylglycine. It may function as a metabolite repair enzyme .
Heteromeric transposase endonuclease subunit TnsA-like (TnsA-like)
Type: Family

This entry represents a group of proteins from actinomycetes that resemble the endonuclease subunit TsnA of the multimeric transposase of Tn7 and its relatives. Members of this family occur in genomic neighbourhoods that suggest a similar role in transposition.
SPW_0924-like (SPW_0924-like)
Type: Family

This entry represent a family of small (less than 44 amino acid residues) uncharacterised proteins, that are found exclusively in the Actinobacteria (mostly Streptomyces). The N-terminal half is organised like a signal peptide, beginning Met-Arg and then continuing with a hydrophobic stretch that is unusually rich in alanine. The C-terminal region has a nearly invariant motif TSPxPLLTTVP. The function of these proteins is unknown.
Cyclin-dependent kinase 20-like, catalytic domain (CDK20-like_STKc)
Type: Domain

This entry represents the catalytic domain of CDK20/CCRK, which is also found in the putative cyclin-dependent kinase F-2, a poorly characterised protein from rice.

Cyclin-dependent kinases (CDKs) are the catalytic subunits of a large family of serine/threonine protein kinases (STKs). Cyclin-dependent kinase 20 (CDK20), also known as Cell cycle-related kinase (CCRK), was previously called p42 . Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) is a key regulator of cell cycle checkpoints controlling cell proliferation/growth, which is essential for the activation of CDK2 . It is indispensable for cell growth and has been implicated in the development of multiple cancers , such as in the progression of glioblastoma multiforme .

In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure . CDK20 also plays an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes .
F-box only protein 8, F-box domain (FBXO8_F-box)
Type: Domain

This entry represents the F-box domain of F-box only protein 8 (FBXO8, also called FBX8, or F-box/SEC7 protein FBS). FBXO8 is a novel component of F-box proteins which contains an F-box domain and a Sec7 domain. This protein was originally identified as a Skp1-binding protein. It is involved in the ubiquitin-dependent proteolytic pathway. It acts as a metastasis suppressor that functions through mTOR signaling pathway . FBXO8 may promote the activation of ADP-ribosylation factor (ARF) through replacement of GDP with GTP . The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.
Transposase IS1249 (IS1249_transpos)
Type: Family

Members of this family belong to the IS1249 subfamily branch of the broader IS256 family of transposases. This group differs from the main branch by having an N-terminal region with two pairs of closely spaced Cys residues.
Beta-alanine-activating enzyme, AMP-binding domain (AASDH_AMP)
Type: Domain

This entry representes the N-terminal AMB-binding domain (also known as adenylation domain) present in human Beta-alanine-activating enzyme (AASDH) and similar proteins mainly found in vertebrates. AASDH, also known as Acyl-CoA synthetase family member 4 (ACSF4), comprises a putative AMP-binding domain similar to those of bacterial non-ribosomal peptide synthetases, a putative phosphopantetheine attachment site, and a C-terminal PQQDH (pyrroloquinoline quinone dehydrogenase)-related domain .
RNA endonuclease, cap-snatching, bunyaviral (CapSnatch_bunyavir)
Type: Domain

This entry represents a domain from an RNA endonuclease region associated with cap-snatching for mRNA production by RNA viruses . This domain usually is part of a multifunctional protein, the L protein responsible for RNA-dependent RNA polymerase activity. Cap-snatching is a viral alternative to synthesizing a eukaryotic-like mRNA cap itself . Members of this group are found in bunyavirales.
Ecdysone-induced protein 78C-like, ligand binding domain (NR_LBD_DmE78-like)
Type: Domain

This entry represents the ligand binding domain (LBD) of Drosophila E78 and its homologues.

Drosophila ecdysone-induced protein 78 (E78) is a transcription factor belonging to the nuclear receptor superfamily. E78 is a product of the ecdysone-inducible gene found in an early late puff locus at position 78C during the onset of Drosophila metamorphosis . It is expressed throughout the germline during oogenesis, and is important for proper egg production and for the maternal control of early embryogenesis . Two isoforms of E78, E78A and E78B, are expressed from two nested transcription units.

An E78 orthologue from the Platyhelminth Schistosoma mansoni (SmE78) has also been identified . It is the first E78 orthologue known outside of the molting animals - the Ecdysozoa. SmE78 may be involved in transduction of an ecdysone signal in S. mansoni (

), consistent with its function in Drosophila. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, E78-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a non-conserved hinge and a C-terminal ligand binding domain (LBD) .
NGRR domain (NGRR_dom)
Type: Domain

This entry represents a domain that is found in the N-terminal region of proteins with extended collagen-like Gly-rich repeat regions, from which its name originates (N-terminal-to-Gly-Rich-Repeat). This domain is identified in proteins from order Bacillales. Its function is unknown.
Potassium voltage-gated channel subfamily F member 1-like, BTB/POZ domain (KCNF1-like_BTB_POZ)
Type: Domain

This entry represents BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain present in human Potassium voltage-gated channel subfamily F member 1 (KCNF1) and similar potassium voltage-gated channel proteins from vertebrates. Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCNF1 functions as a regulatory alpha-subunit of voltage-gated potassium channel that, when coassembled with Kv2.1, can modulate gating in a physiologically relevant manner. It forms hetero-tetrameric channels (with other alpha subunits) through its BTB/POZ domain, also known as tetramerisation (T1) domain, which is a versatile protein-protein interaction motif .
MazG-like, C-terminal domain (NTP-PPase_MazG-like_C)
Type: Domain

MazG is a NTP-PPase that hydrolyzes all canonical NTPs into their corresponding nucleoside monophosphates and pyrophosphate . The prototype of this family is MazG proteins from Escherichia coli (EcMazG) that represents the most abundant form consisting two sequence-related domains in tandem; this entry represents the C-terminal MazG-like domain.

EcMazG functions as a regulator of cellular response to starvation by lowering the cellular concentration of guanosine 3',5'-bispyrophosphate (ppGpp). EcMazG exists as a dimer. Each monomer contains two tandem MazG-like domains with similarly folded globular structures. However, only the C-terminal domain has well-ordered active sites and exhibits an NTPase activity responsible for the regulation of bacterial cell survival under nutritional stress . Divalent ions, such as Mg2 or Mn2, are required for activity, along with structural features such as EEXX(E/D) motifs and key basic catalytic residues. It has been shown that the C-terminal NTPase activity is responsible for regulation of bacterial cell survival under nutritional stress.
Mobilization protein BfmA-like, N-terminal domain (BfmA-like_N)
Type: Domain

This entry represents the N-terminal domain of the mobilisation protein BfmA from Bacteroides fragilis (

) and similar sequences mainly found in bacteroidetes. BfmA was identified as a mobilisation protein for a pathogenicity island that includes fragilysin (Bacteroides fragilis toxin, or BFT) and the fragilysin family metalloproteinase MP-II. BfmA has partner proteins BfmB (a member of

) and BfmC. The distantly related protein BtgA, also found in Bacteroides fragilis, is a mobilisation factor for antibiotic resistance .
EMYY-motif containing lipoprotein (EMYY_lipop)
Type: Family

Members of this family are lipoproteins, about 300 amino acid residues long, found broadly in the genus Staphylococcus and in some related species. Most of these proteins contain an N-terminal lipoprotein lipid attachment site.
YdcK-like (YdcK-like)
Type: Family

This entry includes YdcK and its homologues, an uncharacterised protein from Escherichia coli (

). This protein is predicted to be distantly related to LpxA-like enzymes and, similarly, to adopt a single-stranded left-handed β-helix. Members of this family are found mainly in gammaproteobacteria.
MazG-like, N-terminal domain (NTP-PPase_MazG-like_N)
Type: Domain

MazG is a NTP-PPase that hydrolyzes all canonical NTPs into their corresponding nucleoside monophosphates and pyrophosphate . The prototype of this family is MazG proteins from Escherichia coli (EcMazG) that represents the most abundant form consisting two sequence-related domains in tandem.

EcMazG functions as a regulator of cellular response to starvation by lowering the cellular concentration of guanosine 3',5'-bispyrophosphate (ppGpp). EcMazG exists as a dimer. Each monomer contains two tandem MazG-like domains with similarly folded globular structures. However, only the C-terminal domain has well-ordered active sites and exhibits an NTPase activity responsible for the regulation of bacterial cell survival under nutritional stress . Divalent ions, such as Mg2 or Mn2, are required for activity, along with structural features such as EEXX(E/D) motifs and key basic catalytic residues. It has been shown that the C-terminal NTPase activity is responsible for regulation of bacterial cell survival under nutritional stress.

This entry represents the N-terminal MazG-like domain. It has been suggested that the N-terminal domain of EcMazG might have a house-cleaning function by hydrolyzing noncanonical NTPs whose incorporation into the nascent DNA leads to increased mutagenesis and DNA damage. This entry also includes mycobacterial MazG (MtMazG), which, unlike EcMazG, contains one MazG-like domain, homologous to EcMazG N-terminal domain containing key residues required for Mg2 coordination and substrate binding .
HMG domain-containing protein 4, HMG-box (HMGXB4_HMG-box)
Type: Domain

HMG box-containing protein 4 (HMGXB4), also known as high mobility group protein 2-like 1 (HMG2L1), or protein HMGBCG, is a non-histone chromosomal protein that negatively regulates Wnt/beta-catenin signaling during development. It plays a role in the hematopoietic system . This entry represents the HMG-box of HMGXB4 and closely related proteins.
Uncharacterized protein y4cF-like (Y4cF-like)
Type: Family

This entry represents a group of proteins from alphaproteobacteria that contain the domain of unknown function DUF1612 (

), including the uncharacterized protein y4cF from Sinorhizobium fredii. Members often also possess the HTH DNA binding domain (

), suggesting DNA-binding activity. RHE_PE00001 from Rhizobium etli (

), which also belongs to this family, was shown to be essential for growth on rich medium, despite being encoded on a plasmid .
Type IV secretion system, ComB10-like (T4SS_ComB10-like)
Type: Family

This entry represents the DNA type IV secretion system protein ComB10 (

), a VirB10 homologue from Helicobacter pylori. ComB10 is an outer membrane-associated component of a DNA-translocating type IV secretion system (T4SS) involved in competence. In contrast to most T4SS that translocate protein toxins and other virulence factors into host cells , ComB10 as found in Helicobacter, and the T4SS of Agrobacterium, translocate DNA and function in DNA uptake or release .

The structure of the C-terminal periplasmic domain of ComB10 was determined (

) and consists of a β-barrel capped on both sides with β-hairpins, one of which containing an α-helical insertion that protrudes from the top of the barrel and it is anticipated to be involved in protein-protein interactions .