SII-SWORD/CoKE huggingface dataset:
Relaxosome protein TraM (TRelaxosome_TraM)
Type: Family

TraM is a plasmid encoded DNA-binding protein that is essential for conjugative transfer of F-like plasmids (e.g. F, R1, R100 and pED208) between bacterial cells. Bacterial conjugation, a form of horizontal gene transfer between cells, is an important contributor to bacterial genetic diversity, enabling virulence and antibiotics resistance factors to rapidly spread in medically important human pathogens.

Mutation studies have shown that TraM is required for normal levels of transfer gene expression as well as for efficient site-specific single-stranded DNA cleavage at the origin of transfer (oriT). TraM tetramers bridge oriT to a key component of the conjugative pore, the coupling protein TraD. The N-terminal ribbon-helix-helix (RHH) domain of TraM is able to cooperatively bind DNA in a staggered arrangement without interaction between tetramers. This allows the C-terminal TraM tetramerization domains to be free to make multiple interactions with TraD, thus driving plasmid recruitment to the conjugative pore .
Borrelia P83100 (Borrelia_P83)
Type: Family

This family consists of several Borrelia P83/P100 antigen proteins.
Protein of unknown function DUF722 (DUF722)
Type: Family

This family contains several bacteriophage proteins of unknown function.
Choristoneura fumiferana antifreeze (Antifreeze_CF)
Type: Family

Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies . These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.

The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil . The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.

A second insect antifreeze from Tenebrio molitor (

) also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.
Protein of unknown function DUF723 (DUF723)
Type: Family

This family contains several uncharacterised proteins from Neisseria meningitidis. These proteins may have a role in DNA binding.
Protein of unknown function DUF724 (DUF724)
Type: Family

Proteins in this family may be involved in the polar growth of plant cells via transportation of RNAs .
Protein TsetseEP (TsetseEP)
Type: Domain

This domain can be found in tsetseEP, a gut protein from the tsetse Glossina morsitans. Towards the C terminus, the protein contains 59 (EP) repeats .
Receptor-recognising protein Gp38 (Receptor-recog_Gp38)
Type: Domain

T-even bacteriophages recognise their cellular receptors with the free ends of their six long tail fibres. The Gp38 protein from bacteriophage T2 and related phages is located at the tip of the tail fibre, where it recognises the host receptor . OmpC has been identified as the host receptor, and sequence variations appear to be an important determinant of host specificity .

Note this family is not related, either in sequence similairty or function, to the Gp38 protein from bacteriophage T4.
Transcription activator CII (Transcrpt_activ_CII)
Type: Family

The CII protein is a transcription activator, conserved in bacteriophage lambda and related phages, that plays a key role in the decision between lytic or lysogenic phage development. CII is regulated at multiple levels including transcription, translation initiation, mRNA stability, and proteolysis . Conditions that stabilise cII favour lysogenic development.

The lambda CII protein activates three specific promoters, binding to direct repeat sequences rather than the more usual inverted repeats. Structurally, CII is a homotetramer where each monomer is composed of four α helices and a disordered C terminus . The α helical region is responsible for DNA binding and multimerisation. The homotetramer has an unusual spatial arrangement that allows recognition of the direct repeat sequences.
Alpha-L-arabinofuranosidase B, arabinose-binding domain (AbfB_ABD)
Type: Domain

Alpha-L-arabinofuranosidase B (AkAbfB) comprises two domains: a catalytic domain and an arabinose-binding domain (ABD). This entry represents the ABD domain. ABD has a β-trefoil fold similar to that of carbohydrate-binding module (CBM) family 13 but also with a number of distinctive characteristics, suggesting that it could be classified into a new CBM family .
Tobravirus 2B (Tobravirus_2B)
Type: Family

This family consists of several tobravirus 2B proteins. It is known that the 2B protein is required for transmission by both Paratrichodorus pachydermus and Paratrichodorus anemones nematodes . Transmission of the tobraviruses Tobacco rattle virus by trichodorid vector nematodes requires the viral coat protein (CP) and the 2B protein, a nonstructural protein encoded by RNA2, the smaller of the two viral genomic RNAs. It is hypothesized that the 2B protein functions by interacting with a small, flexible domain located at the C terminus of the CP, forming a bridge between the virus particle and the internal surface of the vector nematode feeding apparatus .
Virulence-associated protein E-like domain (VapE-like_dom)
Type: Domain

This domain is found in VapE (virulence-associated protein E,

) from Dichelobacter nodosus and similar proteins, mainly from bacteria.
RNA polymerase, 22kDa subunit, poxviral (RNA_Pol_22kDa_poxvir)
Type: Family

Vaccinia viral RNA synthesis is carried out by a virus coded, multi-subunit, eukaryotic-like RNA polymerase. RNA polymerase subunits are synthesized throughout infection and the assembled RNA polymerase is packaged into nascent virions late in infection. The RNA polymerase exists in two different forms, one specific for early genes and one specific for late genes. Both forms of the RNA polymerase have in common eight subunits, ranging in size from 147 to 7kDa This family consists of several poxvirus DNA-dependent RNA polymerase 22kDa subunits.
Baculovirus occlusion-derived virus envelope, E25 (Baculo_ODV-E25)
Type: Family

This family consists of several nucleopolyhedrovirus occlusion-derived virus envelope E25 proteins. The N terminus of this protein is extremely hydrophobic, studies suggest that this defined hydrophobic domain is sufficient to direct the protein to induced membrane microvesicles within a baculovirus-infected cell nucleus and the viral envelope. In addition, movement of the protein into the nuclear envelope may initiate through cytoplasmic membranes, such as endoplasmic reticulum, and that transport into the nucleus may be mediated through the outer and inner nuclear membrane .
Copper resistance B precursor (Cu-R_B_prcur)
Type: Family

This family consists of several bacterial copper resistance proteins. Copper is essential and serves as a cofactor for more than 30 enzymes yet a surplus of copper is toxic and leads to free radical formation and oxidation of biomolecules. Therefore, copper homeostasis is a key requisite for every organism. CopB serves to extrude copper when it approaches toxic levels and has been shown to act as an ATPase (

).
SH3-binding 5 (SH3BP5)
Type: Family

This family consists of several eukaryotic SH3 domain-binding protein 5 or c-Jun N-terminal kinase (JNK)-interacting proteins (SH3BP5 or Sab). Sab binds to and serves as a substrate for JNK in vitro, and has been found to interact with the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk). Inspection of the sequence of Sab reveals the presence of two putative mitogen-activated protein kinase interaction motifs (KIMs) similar to that found in the JNK docking domain of the c-Jun transcription factor, and four potential serine-proline JNK phosphorylation sites in the C-terminal half of the molecule .

This entry also includes REI-1 and REI-2 from C. elegans. REI-1 is a guanine nucleotide exchange factors (GEFs) for RAB-11. It functions in early embryos .
Protein of unknown function DUF726 (DUF726)
Type: Family

This family consists of transmembrane and coiled-coil domain-containing proteins found in animal and plant organisms, uncharacterised membrane proteins in eukaryotes, and uncharacterised proteins in prokaryotes. Some of these proteins have an alpha/beta hydrolase domain

.
Phospholipase-like (PLipase-like)
Type: Family

This family contains several phospholipase-like proteins from Arabidopsis thaliana and other members of the Streptophyta which are homologous to PEARLI 4.
Aspartyl beta-hydroxylase/Triadin domain (Asp-B-hydro/Triadin_dom)
Type: Domain

This domain is found in members of the junctin, junctate and aspartyl beta-hydroxylase protein families. Junctate is an integral ER/SR membrane calcium binding protein, which comes from an alternatively spliced form of the same gene that generates aspartyl beta-hydroxylase and junctin . Aspartyl beta-hydroxylase catalyses the post-translational hydroxylation of aspartic acid or asparagine residues contained within epidermal growth factor (EGF) domains of proteins .

This domain is also found in several eukaryotic triadin proteins. Triadin is a ryanodine receptor and calsequestrin binding protein located in junctional sarcoplasmic reticulum of striated muscles .
Flagellar transcriptional activator FlhC (FlhC)
Type: Family

This family consists of several bacterial flagellar transcriptional activator (FlhC) proteins. FlhC combines with FlhD to form a regulatory complex in Escherichia coli, this complex has been shown to be a global regulator involved in many cellular processes as well as a flagellar transcriptional activator .
Neuroendocrine 7B2 precursor (Secretogranin_V)
Type: Family

Prohormone convertases (PCs) 1 and 2 are a family of eukaryotic subtilisins thought to mediate the proteolytic cleavage of many peptide precursors . Protein 7B2 (secretogranin V) functions as a molecular chaperone for PC2, preventing its premature activation in the regulated secretory pathway . 7B2 represents a potent inhibitor of PC2, and it is also required for the activation of PC2, which is synthesised as a zymogen. Protein 7B2 has an N-terminal activation domain and a C-terminal (CT) inhibitory domain (MEROPS inhibitor family I21), separated by a furin cleavage site . 7B2 is synthesised as a precursor protein that is cleaved into the N-terminal fragment and the C-terminal peptide .

7B2 has been linked to neurodegenerative diseases. It may act as an anti-aggregation chaperone . However, in an APP model mouse 7B2 knockout has been shown to reduce rather than enhance plaque burden .
A1 cistron-splicing factor, AAR2 (AAR2)
Type: Family

This family consists of several eukaryotic AAR2-like proteins. The Saccharomyces cerevisiae protein AAR2 is involved in splicing pre-mRNA
of the a1 cistron and other genes that are important for cell growth .
Protein of unknown function DUF736 (DUF736)
Type: Family

This family consists of several uncharacterised bacterial proteins of unknown function.
SDA1, middle domain (SDA1_MD)
Type: Domain

This domain is found in several SDA1 protein homologues. SDA1 is a Saccharomyces cerevisiae protein which is involved in the control of the actin cytoskeleton. The protein is essential for cell viability and is localised in the nucleus .
Keratin-associated protein, PMG type (KRTAP_PMG)
Type: Family

This entry represents the keratin-associated proteins, PMG type . The major structural proteins of mammalian hair are the hair keratin intermediate filaments (KIFs) and the keratin-associated proteins (KRTAPs). In the hair cortex, hair keratins are embedded in an inter-filamentous matrix consisting of KRTAPs which are essential for the formation of a rigid and resistant hair shaft as a result of disulphide bonds between cysteine residues. There are essentially three groups of KRTAPs, viz: the high-sulphur (HS) and ultra-high-sulphur (UHS) KRTAPs (cysteine content: 16-30 and >30 mol%, respectively) and the high-glycine/tyrosine (HGT: 35-60 mol% glycine and tyrosine) KRTAPs.
Poxvirus A2.5L (Poxvirus_A2.5L)
Type: Family

This family represents A2.5L from Vaccinia virus, also known as Protein OPG128, and similar sequences from poxvirus. A2.5L is a late protein which probably participates in disulfide bond formation by functioning as a thiol-disulfide transfer protein between membrane-associated OPG072 and OPG08 . It is an all-α-helical protein with a conserved Cxx(x)C motif in the N-terminal α-helix. It appears to be an integral component of intracellular virions .
Holin-like, BlyB (Holin-like_BlyB)
Type: Family

This entry represents the borrelial prophage-encoded protein BlyB. Originally BlyB and its partner, the membrane-bound protein BlyA, were thought to comprise a haemolysis system. It is now thought, however, that BlyA and BlyB function instead as a holin or holin-like system .
Baculovirus immediate-early (Baculo_IE-1)
Type: Family

This entry contains the Baculovirus immediate-early protein IE-0.
Bystin (Bystin)
Type: Family

Trophinin and tastin form a cell adhesion molecule complex that potentially mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of implantation. Trophinin and tastin bind to an intermediary cytoplasmic protein called bystin. Bystin may be involved in implantation and trophoblast invasion because bystin is found with trophinin and tastin in the cells at human implantation sites and also in the intermediate trophoblasts at invasion front in the placenta from early pregnancy . This family also includes the Saccharomyces cerevisiae protein ENP1. ENP1 is an essential protein in S. cerevisiae and is localised in the nucleus . It is thought that ENP1 plays a direct role in the early steps of rRNA processing as enp1 defective S. cerevisiae cannot synthesise 20S pre-rRNA and hence 18S rRNA, which leads to reduced formation of 40S ribosomal subunits .
Malonyl-CoA decarboxylase, C-terminal (Malonyl_CoA_deC_C)
Type: Domain

Malonyl-CoA, in addition to being an intermediate in the
de novo
synthesis of fatty acids, is an inhibitor of carnitine palmitoyltransferase I, the enzyme that regulates the transfer of long-chain fatty acyl-CoA into mitochondria, where they are oxidised. After exercise, malonyl-CoA decarboxylase participates with acetyl-CoA carboxylase in regulating the concentration of malonyl-CoA in liver and adipose tissue, as well as in muscle. Malonyl-CoA decarboxylase is regulated by AMP-activated protein kinase (AMPK) .

This entry represents the C-terminal catalytic domain of Malonyl-CoA decarboxylase .
African swine fever virus L11L (ASFV_L11L)
Type: Family

L11L is an integral membrane protein of the African swine fever virus, which is expressed late in the virus replication cycle. The protein is thought to be non-essential for growth
in vitro
and for virus virulence in domestic pigs

].
Scorpion short chain toxin, chloride channel inhibitor (Scorpion_toxinS_Cl_inh)
Type: Family

Short scorpion toxin chloride channel inhibitors are short-chain neurotoxins (SCNs), which block small-conductance chloride channels. They are 30-40-residue long and contain four intramolecular disulphide bridges, which have been assigned as C1-C4, C2-C6, C3-C7 and C5-C8 .

The global fold of the scorpion short toxin chloride channel inhibitor subfamily is an α-helix packed on a two-stranded β-sheet. The structure also contains a short fragment in an extended form. The two antiparalllel β-strands are connected by a type I β-turn. The four disulphide bridges help to maintain a very compact structure by heavily attaching the N-terminal and C-terminal ends to the α-helix .
Dinoflagellate luciferase, N-terminal (Dino_Luciferase_N)
Type: Domain

Proteins in this entry belong to a family of dinoflagellate luciferase and luciferin binding proteins. Luciferase is involved in catalysing the light emitting reaction in bioluminescence and luciferin binding protein (LBP) is known to bind to luciferin (the substrate for luciferase) to stop it reacting with the enzyme and therefore switching off the bioluminescence function. The expression of these two proteins is controlled by a circadian clock at the translational level, with synthesis and degradation occurring on a daily basis .

This entry consists of a presumed N-terminal domain that is conserved between dinoflagellate luciferase and luciferin binding proteins. This domain is not, however, the catalytic part of the protein. It has been suggested that this region may mediate an interaction between LBP and Luciferase or their association with the vacuolar membrane .
Taste receptor type 2 (TAS2R)
Type: Family

This family consists of several forms of taste receptor proteins (TAS2Rs) predominantly found in mammals. TAS2Rs are G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate epithelia and are organised in the genome in clusters. The proteins are genetically linked to loci that influence bitter perception in mice and humans . These receptors may play a role in sensing the chemical composition of the gastrointestinal content.
Herpesvirus latent membrane 1 (Herpes_LMP1)
Type: Family

This family consists of several latent membrane protein 1 or LMP1s mostly from Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4). LMP1 of HHV-4 is a 62-65kDa plasma membrane protein possessing six membrane spanning regions, a short cytoplasmic N terminus and a long cytoplasmic carboxy tail of 200 amino acids. HHV-4 virus latent membrane protein 1 (LMP1) is essential for HHV-4 mediated transformation and has been associated with several cases of malignancies. HHV-4-like viruses in Macaca fascicularis (Cynomolgus monkeys) have been associated with high lymphoma rates in immunosuppressed monkeys .
Bombinin (Bombinin)
Type: Family

This family consists of Bombinin and Maximin proteins from Bombina maxima (Giant fire-bellied toad). Two groups of antimicrobial peptides have been isolated from skin secretions of B. maxima. Peptides in the first group, named maximins 1, 2, 3, 4 and 5, are structurally related to bombinin-like peptides (BLPs). Unlike BLPs, sequence variations in maximins occurred all through the molecules. In addition to the potent antimicrobial activity, cytotoxicity against tumour cells and spermicidal action of maximins, maximin 3 possessed a significant anti-Simian-Human immunodeficiency virus (HIV) activity. Maximins 1 and 3 have been found to be toxic to mice. Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous with bombinin H peptides .
Peptidase M61, catalytic domain (Peptidase_M61_catalytic)
Type: Domain

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to the MEROPS peptidase family M61 (glycyl aminopeptidase family, clan MA(E)).The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH. The type example is glycyl aminopeptidase from Sphingomonas capsulata.
MICOS complex subunit MIC19/MIC25 (MIC19/MIC25)
Type: Family

MIC19 (also known as ChChd3) and MIC25 (also known as ChChd6) are components of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane . MIC19 plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology .
Gcn5-related N-acetyltransferase (GNAT) domain, ATAT-type (GNAT_ATAT)
Type: Domain

The N-acetyltransferases (NAT) (EC 2.3.1.-) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction implicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodeling. The Gcn5-related N-acetyltransferases (GNAT) catalyze the transfer of the acetyl from the CoA donor to a primary amine of the acceptor. The GNAT proteins share a domain composed of four conserved sequence motifs A-D . This GNAT domain is named after yeast GCN5 (from General Control Nonrepressed) and related histone acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residues of amino terminal histone tails, resulting in transcription activation. Another category of GNAT, the aminoglycoside N-acetyltransferases, confer antibiotic resistance by catalyzing the acetylation of amino groups in aminoglycoside antibiotics . GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes .

The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 β strands (B) and 4 helices (H) in the topology B1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may be from the same monomer or contributed by another . Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core , while the N-terminal motif C (B1-H1) is less conserved.

This entry represents the ATAT-type of the GNAT domain . Proteins containing this domain include alpha-tubulin N-acetyltransferase, originally known as mechanosensory abnormality protein 17 (Mec-17), as it is the protein product of one of the 18 genes required for the development and function of the touch receptor neuron for gentle touch . Mec-17 specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules . It is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules . It may affect microtubule stability and regulate microtubule dynamics.
Protein of unknown function DUF720 (DUF720)
Type: Family

This family consists of several uncharacterised Chlamydia proteins of unknown function.
GSKIP domain (GSKIP_dom)
Type: Domain

This domain is found in GSK3-beta interaction protein (GSKIP), which binds to GSK3beta . It is also found as a short domain towards the N terminus in clustered mitochondria protein, also known as clueless in Drosophila, which is involved in proper cytoplasmic distribution of mitochondria .
Tobacco rattle virus, 16 kDa protein (Tobacco_rattle_virus_16kDa)
Type: Family

This entry is represented by the Tobacco rattle virus, 16 kDa protein and similar proteins from Tobravirus. This weak suppressor of RNA silencing is not essential for the systemic spread of the plant virus . However, it is required for the transient invasion of the meristem .
Domain of unknown function DUF732 (DUF732)
Type: Domain

This entry represents several uncharacterised Mycobacterium tuberculosis proteins of unknown function.
Protein of unknown function DUF733 (DUF733)
Type: Family

This family consists of several uncharacterised Drosophila melanogaster proteins of unknown function.