SII-SWORD/CoKE huggingface dataset:
AmiS/UreI transporter (AmiSUreI_transpt)
Type: Family

Helicobacter pylori is a Gram-negative, ureolytic bacteria that can colonise the human stomach. It does not survive in a medium with a pH less than 4.0 unless urea is present, preferring a neutral pH. Gastric juice urea is able to rapidly access intrabacterial urease when the periplasmic pH falls below approximately 6.2 owing to pH-gating of a urea channel, UreI. UreI is a six-transmembrane segment protein that is homologous to the amiS genes of the amidase gene cluster and to UreI of Helicobacter hepaticus and Streptococcus salivarius. UreI in H. pylori and H. hepaticus can transport urea only at acidic pH, whereas that of S. salivarius is open at both neutral and acidic pH .

The amiS gene encodes an 18kDa protein with a high content of hydrophobic residues. It has six transmembrane helices. AmiB and AmiS resemble two components of an ABC transporter system .

This family includes UreI and proton gated urea channel as well as putative amide transporters .
DNA-binding protein 7a-e (DNA-bd_7a-e_arc)
Type: Family

This family includes DNA-binding protein 7a-e (DN7A-E) from hyperthermophilic archaebacterium. There are five 7kDa DNA-binding proteins, 7a-7e, found as monomers in the cell. These proteins may be involved in maintaining the integrity of the genome at high temperature . DNA-binding protein 7a (also known as Ssoa1) has RNA endonuclease activity with a narrow substrate specificity; the cleavage products are 3'-phosphooligonucleotides . Protein 7e shows the tightest DNA-binding ability . DN7d, also known as Sso7d, is a small chromatin protein that binds to DNA with high affinity in a non-cooperative manner without sequence preference . Sul7d compacts DNA by both DNA bending and bridging which allows DNA to be packaged into highly condensed structures .
Cytochrome c oxidase, subunit VIb (Cyt_c_oxidase_su6B)
Type: Family

Cytochrome c oxidase (

) is an oligomeric enzymatic complex that is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptide subunits. One of these subunits is the potentially haem-binding subunit, VIb, which is encoded in the nucleus . Subunit VIb is one of three mammalian subunits that lacks a transmembrane region. It is located on the cytosolic side of the membrane and helps form the dimer interface with the corresponding subunit on the other monomer complex .
InsA N-terminal zinc ribbon domain (InsA_N_dom_Znf)
Type: Domain

Insertion elements are mobile elements in DNA, usually encoding proteins required for transposition, for example transposases. Protein InsA is absolutely required for transposition of insertion element 1.

This entry represents a short zinc binding domain found in IS1 InsA family protein. It is found at the N terminus of the protein and may be a DNA-binding domain.
Antitermination protein (Antitermntn)
Type: Family

This entry consists of antitermination proteins found in bacteriophages, such as protein Q from phage lambda, and some bacterial homologues. Protein Q positively regulates expression of the phage late gene operon by binding to the bacterial host RNA polymerase (RNAP) and modifying it. This protein binds a specific DNA Q-binding element (QBE) and interacts with RNAP. The modified RNAP can read without pausing and through transcription terminators preceding late genes . It participates in the lysis-lysogeny decision by activating the expression of the late lytic genes . The structure of Q from bacteriophage 21 revealed that it forms a torus, that narrows and extends the RNAP RNA-exit channel and extrudes the linked RNA, preventing the formation of pause and terminator hairpins .
Flagellin phase1 repressor (Flag1_repressor)
Type: Family

Flagellin is the subunit which polymerises to form the filaments of bacterial flagella. The proteins in this family are transcriptional repressors of phase-1 flagellin genes.
RING finger protein Z, zinc finger (Z_RING_Znf)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the RING zinc finger domain of 'RING finger protein Z', a small polypeptide found in some negative-strand RNA viruses including Lassa fever virus, which plays a crucial role in virion assembly and budding. RING finger Z has been shown to interact with several host proteins, including promyelocytic leukemia protein and the eukaryotic translation initiation factor 4E . It is sufficient in the absence of any other viral proteins to release virus-like particles from the infected cell . This protein is also responsible for arenavirus superinfection exclusion; expression of this protein in a host cell strongly and specifically inhibits areanavirus transcription and replication .

The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions . There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'. The RING domain is a protein interaction domain which has been implicated in a range of diverse biological processes. Several 3D-structures for RING-fingers are known . The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is:

C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C

Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second.
Viral protein of unknown function DUF325 (DUF325)
Type: Family

This is a family of uncharacterised proteins from Alphabaculovirus.
MYG1 exonuclease (MYG1_exonuclease)
Type: Family

This family includes MYG1 exonuclease from human and its orthologues, a 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. It is involved in regulating spatially segregated organellar RNA processing, acting as a coordinator of nucleo-mitochondrial crosstalk . In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins . Overexpression of MYG1 has been associated with the autoimmune disorder vitiligo, suggesting that MYG1 may play some role in human innate immunity . Studies in yeast suggested a potential antiviral function of MYG1 .
Transcription initiation factor TFIID subunit 12 domain (TFIID_TAF12_dom)
Type: Domain

TBP-associated factor 12 (TAF12) is one of several TAFs that bind TBP and are involved in forming the TFIID complex. TAF12 interacts with TAF4 and makes a novel histone-like heterodimer that binds DNA and has a core promoter function of a subset of genes .

This entry represents a domain found in TAF12.

TFIID is one of several General Transcription Factors (GTFs), which also include TFIIA, TFIIB, TFIIE, TFIIF and TFIIH, that are involved in the accurate initiation of transcription by RNA polymerase II in eukaryotes. TFIID plays an important role in the recognition of promoter DNA and assembly of the pre-initiation complex. Human transcription initiation factor TFIID is composed of the TATA-binding protein (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription .
D-alanyl carrier protein (DltC)
Type: Family

This entry represents D-alanyl carrier protein DltC, which is part of the operon for incorporation of D-Ala residues into lipoteichoic acids (LTAs), which requires the activity of four gene products (DltA to DltD). DltA is a cytoplasmic D-alanine-D-alanyl carrier protein ligase that catalyses the D-alanylation of the D-alanyl carrier protein DltC (or Dcp); DltB is a transmembrane protein thought to be involved in the efflux of activated D-alanine to the site of acylation; and DltD is thought to be a membrane-associated protein that may have multifunctional activities (hydrolysis of mischarged DltC, facilitation of D-alanine ligation to DltC and D-alanylation of LTAs) .

These proteins are involved in the biosynthesis of D-alanyl-lipoteichoic acid in bacteria. They are major wall and membrane components of most Gram-positive bacteria . Streptococcus pneumoniae is one of the few species of low-G and C Gram-positive bacteria that do not contain d-alanine in teichoic acids . d-alanine residues are thought to protect this human pathogen against the actions of cationic antimicrobial peptides. Mammals use antimicrobial peptides to protect themselves from invasive infectious agents such as Group A streptococcus (GAS), which causes necrotising fasciitis and toxic shock syndrome . Teichoic acids and D-alanylation of teichoic acids are required for colony spreading in Staphylococcus aureus .
Acyl carrier protein (ACP)
Type: Family

There are two types of fatty acid synthase systems. The type I system is found in metazoans and is carried out by a multifunctional polypeptide with multiple active sites. In contrast, the type II system found in bacteria and plants consists of a set of discrete monofunctional proteins, each encoded by a separate gene. ACP1 is central to both of these pathways because it functions to ferry the pathway intermediates between active site centres or enzymes. ACPs are also critical to the function of other metabolic pathways such as polyketide synthases.
Nematode insulin-like peptide, beta type (Nem_insulin-like_b-type)
Type: Family

Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver . Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth .

This entry represents Caenorhabditis elegans insulin-like peptides , beta type.
Phytocyanin domain (Phytocyanin_dom)
Type: Domain

Among the blue copper proteins with a single type I (or "blue") mononuclear
copper site, the plant-specific phytocyanins constitute a distinct subfamily
that can be further subdivided into the families of uclacyanins, stellacyanins,
plantacyanins, and early nodulins. Stellacyanins have a blue copper
coordinated by two His, one Cys and one Gln. In plantacyanins and uclacyanins,
the ligands of the type-I Cu sites are two His, one Cys and one Met . Early nodulins lack amino acid residues that coordinate Cu, so they are believed to be involved in unknown processes without binding Cu . Phytocyanins are found in chloropasts of higher plants.

The phytocyanin domain has a core of seven polypeptide strands arranged as a
β-sandwich comprising two β-sheets, β-sheet I and β-sheet II. β-sheet I consists of three β-strands and β-sheet II
consists of four β-strands. A disulfide bridge close the metal centre is
characteristic for phytocyanins, in contrast to azurins, pseudoazurins, and
plastocyanins, where a disulfide bond is located on the distal side of the
β-barrel. This disuldide bridge may play a crucial role in maintaining the
tertiary structure of the protein and/or the formation of the copper binding
centre because one of the His ligands of copper is followed directly by a
bridging Cys residue . Some members of this group of proteins may not bind copper due to the lack of key residues.
Rubrerythrin, diiron-binding domain (Rr_diiron-bd_dom)
Type: Domain

This entry represents the N-terminal diiron-binding domain of Rr, which has a has a ferritin-like fold .

Rubrerythrin (Rr) is a fusion protein containing an N-terminal diiron-binding domain and a C-terminal domain homologous to rubredoxin . This protein has been related to the response to oxidative stress .

The 3-D structure of Desulphovibrio vulgaris rubrerythrin has been solved . The structure reveals a tetramer of two-domain
subunits. In each monomer, the N-terminal 146 residues form a four-α-helix bundle containing the diiron-oxo site (centre I), and the C-terminal 45 residues form a rubredoxin-like FeS4 domain.
Large ribosomal subunit protein uL24 (Ribosomal_uL24)
Type: Family

Ribosomal protein uL24 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues.

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 .
CD40 ligand (CD40L)
Type: Family

CD40 ligand (CD40L) is a transmembrane protein belonging to the Tumour Necrosis Factor (TNF) superfamily. It can be found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas . CD40L is importance for effective interaction with CD40 and the subsequent intracellular signalling . It is involved in B-cell proliferation and immunoglobulin class switching .

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
HhH-GPD domain (HhH-GPD_domain)
Type: Domain

The HhH-GPD superfamily gets its name from its hallmark helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate . This domain is found in a diverse range of structurally related DNA repair proteins that include: endonuclease III,

and DNA glycosylase MutY, an A/G-specific adenine glycosylase. Both of these enzymes have a C-terminal iron-sulphur cluster loop (FCL). The methyl-CPG binding protein (MBD4) also contain a related domain that is a thymine DNA glycosylase . The family also includes DNA-3-methyladenine glycosylase II

, 8-oxoguanine DNA glycosylases and other members of the AlkA family.
Potassium channel, inwardly rectifying, Kir3.4 (K_chnl_inward-rec_Kir3.4)
Type: Family

Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release . To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x .

Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N-and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero-or homomeric .

The Kir3.x channel family is gated by G-proteins following G-protein coupled receptor (GPCR) activation. They are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G-protein beta-gamma subunits released from G-protein heterotrimers of the G(i/o) family upon appropriate receptor stimulation.

Kir3.4 is thought to associate with Kir3.1, to form hetero-tetrameric acetylcholine-activated K+ channels, in the heart. Their activation, following stimulation of the vagus nerve, leads to slowing of the heart, and reduction in contractile force. In the brain, Kir3.4 distribution has been found to be quite restricted, being found in some neuronal populations, such as Purkinje cells and neurones of the globus pallidus and the ventral pallidum . A recent study has suggested that Kir3.4 may confer mechano-sensitive properties on Kir channels, since channels containing it are inactivated by membrane stretch forces .

Mutations of the Kir3.4 gene have been linked to Long QT syndrome 13 (LQT13) and Hyperaldosteronism, familial, 3 (HALD3) .
Type III secretion system lipoprotein SctJ (T3SS_SctJ)
Type: Family

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior. There have been four secretion systems described in animal enteropathogens such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia .

The type III secretion system is of great interest as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis . However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself, type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.

One of the outer membrane protein subunit families, termed "K" here for nomenclature purposes, aids in the structural assembly of the invasion complex . It is also described as a lipoprotein. Members of this family include the Salmonella PrgK and SsaJ , MxiJ from Shigella , YscJ from Yersinia, and from the plant enteropathogens NolT (Rhizobium) and HrcJ Erwinia). The flagellar M-ring protein FliF also shares a low level of similarity, presumably due to evolution of the type III secretion system from the flagellar biosynthetic pathway.
Eukaryotic peptide chain release factor GTP-binding subunit (Sup35)
Type: Family

Sup35 (also known as eRF3) is a translation termination factor that mediates mRNA decay through the regulation of deadenylation .