SII-SWORD/CoKE huggingface dataset:
Ku70 (Ku70)
Type: Family

Ku70 (also known as XRCC6 in animals), a single-stranded DNA-dependent ATP-dependent helicase, is a subunit of the Ku protein, which plays a key role in multiple nuclear processes such as DNA repair, chromosome maintenance, transcription regulation, DNA non-homologous end joining (NHEJ) and V(D)J recombination .

Some findings have implicated yeast Ku in telomeric structure maintenance in addition to non-homologous end-joining. Some of the phenotypes of Ku-knockout mice may indicate a similar role for Ku at mammalian telomeres . Ku70 also plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway .

Both subunits of the eukaryotic Ku heterodimer (Ku70 and Ku80) share a topology comprised of three domains: an α/β N-terminal, a central β-barrel domain and a helical C-terminal arm . Structural analysis of the Ku70/80 heterodimer bound to DNA indicates that subunit contacts lead to the formation of a highly charged channel through which the DNA passes without making any contacts with the DNA bases .
ERCC4 domain (ERCC4_domain)
Type: Domain

This entry represents a structural domain found in several DNA repair nucleases, such as Rad1, XPF and crossover junction endonucleases EME1 and Mus81 . The XPF/Rad1/Mus81-dependent nuclease family specifically cleaves branched structures generated during DNA repair, replication, and recombination, and is essential for maintaining genome stability. The nuclease domain architecture exhibits remarkable similarity to those of restriction endonucleases.
DNA repair protein XPF (XPF)
Type: Family

This entry includes XPF from animals and its fungal orthologues Rad1 from budding yeasts and Rad16 from fission yeasts. Human XPF is a catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. It is involved in homologous recombination that assists in removing interstrand cross-link . This protein is associated with several types of the Xeroderma pigmentosum disorder , XFE progeroid syndrome and a form of Fanconi anemia . Budding yeast Rad1 and Rad10 form an endonuclease that specifically degrades single-stranded DNA .
Glycerol-3-phosphate dehydrogenase, NAD-dependent (G3P_DH_NAD-dep)
Type: Family

NAD-dependent glycerol-3-phosphate dehydrogenase (

) (GPD) catalyzes the reversible reduction of dihydroxyacetone phosphate to glycerol-3-phosphate. It is a cytoplasmic protein, active as a homodimer , each monomer containing an N-terminal NAD binding site . In insects, it acts in conjunction with a mitochondrial alpha-glycerophosphate oxidase in the alpha-glycerophosphate cycle, which is essential for the production of energy used in insect flight .
GTP1/OBG domain (GTP1_OBG_dom)
Type: Domain

The N-terminal domain of GTPase Obg has the OBG fold, which is formed by three glycine-rich regions inserted into a small 8-stranded β-sandwich. These regions form six left-handed collagen-like helices packed and H-bonded together.

Several proteins have recently been shown to contain the 5 structural motifs characteristic of GTP-binding proteins . These include murine DRG protein; GTP1 protein from Schizosaccharomyces pombe; OBG protein from Bacillus subtilis; and several others. Although the proteins contain GTP-binding motifs and are similar to each other, they do not share sequence similarity to other GTP-binding proteins, and have thus been classed as a novel group, the GTP1/OBG family. As yet, the functions of these proteins is uncertain, but they have been shown to be important in development and normal cell metabolism .
Pheromone/general odorant binding protein (PBP/GOBP)
Type: Family

The olfactory receptors of terrestrial animals exist in an aqueous environment, yet detect odorants that are primarily hydrophobic. The aqueous solubility of hydrophobic odorants is thought to be greatly enhanced via odorant binding proteins which exist in the extracellular fluid surrounding the odorant receptors . This family is composed of pheromone binding proteins (PBP) and general-odorant binding proteins (GOBP). GOBPs and PBPs form a subgroup of the insect odorant binding proteins (OBPs). PBPs are male-specific and associate with pheromone-sensitive neurons . This entry also includes Short and Long form salivary proteins having one or two odorant-binding protein-like domains and involved in binding diverse range of compounds .
TOPRIM domain (TOPRIM_dom)
Type: Domain

The Toprim (topoisomerase-primase) domain is a structurally conserved domain of ~100 amino acids that is found in bacterial DnaG-type primases, small primase-like proteins from bacteria and archaea, type IA and type II topoisomerases, bacterial and archaeal nucleases of the OLD family and bacterial DNA repair proteins of the RecR/M family. The Toprim domain can be found alone or in combination with several other domains, such as the ASM domain, the superfamily 2 helicase domain, the superfamily 3 helicase domain, the DnaB interaction domain, the C4 'little finger' domain, the CHC2 zinc finger, the ATPase domain of the HSP90-gyrase-histidine kinase superfamily, the S5 domain, the SET domain, the helix-hairpin-helix (HhH) DNA-binding domain, the mobilisation (MOB) domain or the ATPase domain of the ABC transporter/SMC superfamily. The Toprim domain is a catalytic domain involved in DNA strand breakage and rejoining .

The Toprim domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). Both motifs are preceded by conserved hydrophobic regions predicted to form β-strands. The glutamate residue is probably involved in catalysis, whereas the DxD motif is involved in the co-ordination of Mg(2++) that is required for the activity of all Toprim-containing enzymes. The Toprim domain has a compact α/β fold, with four conserved strands and three helices; with the exception of the second helix and the C-terminal strands, each of these elements contains positions that are highly conserved. The Toprim domain contains three regions that can accommodate variable sized inserts, which are particularly prominent in the topoisomerases .
DNA-directed DNA polymerase, family B (DNA-dir_DNA_pol_B)
Type: Family

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases (

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the
de novo
synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation.
Staphylococcal/Streptococcal toxin, OB-fold (Staph_tox_OB)
Type: Domain

Streptococcus pyogenes (group A streptococcus) cause a wide range of human infections, in a range from acute illness in an initial exposure such as pharyngitis or impetigo to serious and life-threatening infections in humans like toxic shock syndrome (TSS) with or without necrotizing fasciitis and myositis. This pathogen is also associated with development of autoimmune diseases, namely rheumatic fever, acute glomerulonephritis, and guttate psoriasis. Staphylococcus aureus is another major human pathogen that can cause a wide variety of infections, ranging from relatively benign furuncles and soft tissue abscesses to others that are life-threatening, such as infective endocarditis, necrotizing (hemorrhagic) pneumonia, sepsis, and toxic shock syndrome (TSS). The ability of these two pathogens to cause serious infections relays on the production of cell surface and secreted virulence factors, known altogether as superantigens exotoxins which overstimulates many immune processes. Among the cell surface factors, large families of microbial surface components recognising adhesive matrix molecules (MSCRAMMs) and immunoglobulin Fc-binding proteins are included, which are important for host colonisation and interfere with local host immune responses. The secreted virulence factors include multiple cytolysins, proteases, nucleases, and lipases. A hallmark of superantigens is a conserved overall structure containing two major protein domains: an amino-terminal oligosaccharide/oligonucleotide binding (O/B) fold, comprised of a β-barrel, and a carboxy-terminal β-grasp domain made of antiparallel β-strands, with domains connected by a central, diagonal α-helix .

This entry represents the O/B fold domain present in streptococcal exotoxins and staphylococcal enterotoxins. This entry also includes exotoxins found in Streptococcus phage.
YjgF/YER057c/UK114 family (YjgF/YER057c/UK114)
Type: Family

The YjgF/YER057c/UK114 family (also known as the Rid family) of proteins is conserved in all domains of life . A phylogenetic analysis applied by Lambrecht
et al.
has divided the Rid family into a widely distributed archetypal RidA (YjgF) subfamily and seven other subfamilies (Rid1 to Rid7) that are largely confined to bacteria and often co-occur in the same organism with RidA and each other . Although the family members share high levels of protein sequence and structure similarity, their functions vary widely across different species .

Structurally, these proteins are homotrimers with clefts between the monomeric subunits that are proposed to have some functional relevance .

This family includes:

YjgF (also known as RidA or 2-iminobutanoate/2-iminopropanoate deaminase), which displays enamine/imine deaminase activity and can accelerate the release of ammonia from reactive enamine/imine intermediates of the pyridoxal 5'-phosphate-dependent threonine dehydratase (IlvA)

the yeast growth inhibitor YER057c (protein HMF1) that appears to play a role in the regulation of metabolic pathways and cell differentiation

the mammalian 14.5kDa translational inhibitor protein UK114, also known as L-PSP (liver perchloric acid-soluble protein), with endoribonucleolytic activity that directly affects mRNA translation and can induce disaggregation of the reticulocyte polysomes into 80 S ribosomes

RutC from E. coli, which is essential for growth on uracil as sole nitrogen source and is thought to reduce aminoacrylate peracid to aminoacrylate

YabJ from B. subtilis, which is required for adenine-mediated repression of purine biosynthetic genes

Structurally, these proteins are homotrimers with clefts between the monomeric subunits that are proposed to have some functional relevance .

This family includes:

Bacterial YjgF (also known as RidA or 2-iminobutanoate/2-iminopropanoate deaminase), which displays enamine/imine deaminase activity and can accelerate the release of ammonia from reactive enamine/imine intermediates of the pyridoxal 5'-phosphate-dependent threonine dehydratase (IlvA)

The yeast growth inhibitor YER057c (protein HMF1) that appears to play a role in the regulation of metabolic pathways and cell differentiation

The mammalian 14.5kDa translational inhibitor protein or UK114 antigen homologue, also known as L-PSP (liver perchloric acid-soluble protein), which has been reported to show endoribonucleolytic activity that directly affects mRNA translation and can induce disaggregation of the reticulocyte polysomes into 80 S ribosomes and be responsible for the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism

RutC from E. coli, which is essential for growth on uracil as sole nitrogen source and is thought to reduce aminoacrylate peracid to aminoacrylate

YabJ from B. subtilis, which is required for adenine-mediated repression of purine biosynthetic genes
3-hydroxyacyl-CoA dehydrogenase, NAD binding (3-OHacyl-CoA_DH_NAD-bd)
Type: Domain

3-hydroxyacyl-CoA dehydrogenase (

) (HCDH) is an enzyme involved in fatty acid metabolism, it catalyses the reduction of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. Most eukaryotic cells have 2 fatty-acid beta-oxidation systems, one located in mitochondria and the other in peroxisomes. In peroxisomes 3-hydroxyacyl-CoA dehydrogenase forms, with enoyl-CoA hydratase (ECH) and 3,2-trans-enoyl-CoA isomerase (ECI) a multifunctional enzyme where the N-terminal domain bears the hydratase/isomerase activities and the C-terminal domain the dehydrogenase activity. There are two mitochondrial enzymes: one which is monofunctional and the other which is, like its peroxisomal counterpart, multifunctional.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA) HCDH is part of a multifunctional enzyme which also contains an ECH/ECI domain as well as a 3-hydroxybutyryl-CoA epimerase domain .

There are two major regions of similarity in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the centre of the sequence. This represents the N-terminal domain (although in some proteins is central) which is also found in lambda crystallin. Some proteins include two copies of this domain.
Staphylococcal/streptococcal toxin, bacterial (Toxin_bac)
Type: Family

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins belong to a family of related toxins that share the ability to bind to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the Staphylococcus aureus toxic shock syndrome toxin, which shares only a low level of sequence similarity with this group.
Major allergen I polypeptide chain 1 (CH1-like)
Type: Family

This entry includes major allergen I polypeptide chain 1 (Fel d 1 chain 1) from cat and related proteins, such as SCGB1B from mice.

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in Homo sapiens (Human). The nomenclature system uses the first three letters of the genus, followed by the first letter of the species name, followed by a number (additional letters can be added to the name as required to discriminate between similar designations).

Fel d 1 is allergen 1 from Felis silvestris catus (Cat) which is an important agent in human allergic reactions . The protein is expressed in saliva and sebaceous glands. The complete primary structure of Fel d 1 has been determined . The allergen is tetrameric glycoprotein consisting of two disulphide-linked heterodimers of chains 1 and 2, which have been shown to be encoded by different genes. Fel d 1 chains 1 and 2 share structural similarity with uteroglobin, a secretoglobin superfamily member; chain 2 is a glycoprotein with N-linked oligosaccharides.

SCGB1B is an androgen-binding protein that plays a role in mate selection in mice .
5'-Nucleotidase/apyrase (5_nucleotidase/apyrase)
Type: Family

5'-nucleotidases

are enzymes that catalyze the hydrolysis of phosphate esterified at carbon 5' of the ribose and deoxyribose portions of nucleotide molecules. 5'-nucleotidase is a ubiquitous enzyme found in a wide variety of species and which occurs in different cellular locations. The extracellular 5'-nucleotidase from mammals and Discopyge ommata (Electric ray) isozyme is a homodimeric disulphide-bonded glycoprotein attached to the membrane by a GPI-anchor, and requires zinc for its activity. Vibrio parahaemolyticus 5'-nucleotidase (gene nutA) is bound to the membrane by a lipid chain, and requires chloride and magnesium ions for its activity. It is involved in degrading extracellular 5'-nucleotides for nutritional needs.

Periplasmic bacterial 5'-nucleotidase (gene ushA), also known as UDP-sugar hydrolase

, can degrade UDP-glucose and other nucleotide diphosphate sugars. It produces sugar-1-phosphate which can then be used by the cell. UshA seems to require cobalt for its activity. 5'-Nucleotidases are evolutionary related to the periplasmic bacterial 2',3'-cyclic-nucleotide 2'-phosphodiesterase

(gene cpdB), which catalyzes two consecutive reactions: it first converts 2',3'-cyclic-nucleotide to 3'-nucleotide and then acts as a 3'-nucleotidase; and mosquito apyrase

(ATP-diphosphohydrolase) , which catalyzes the hydrolysis of ATP into AMP and facilitates hematophagy by preventing ADP-dependent platelet aggregation in the host.

CD73 (also called ecto-5'-nucleotidase) possesses the enzymatic activity of a 5'-nucleotidase and catalyses the dephosphorylation of purine and pyrimidine ribo-and deoxyribonucleoside monophosphates to their corresponding nucleosides. Triggering of lymphocyte CD73 with mAb causes phosphorylation and dephosphorylation of certain, yet unknown protein substrates . A possible function for CD73 is to regulate the availability of adenosine for interaction with cell surface adenosine receptor by converting AMP to adenosine. In common with other GPI anchored surface proteins CD73 can mediate costimulatory signals in T cell activation .
3-hydroxyacyl-CoA dehydrogenase, conserved site (3-OHacyl-CoA_DH_CS)
Type: Conserved_site

3-hydroxyacyl-CoA dehydrogenase (

) (HCDH) is an enzyme involved in fatty acid metabolism, it catalyzes the reduction of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. Most eukaryotic cells have 2 fatty-acid beta-oxidation systems, one located in mitochondria and the other in peroxisomes. In peroxisomes 3-hydroxyacyl-CoA dehydrogenase forms, with enoyl-CoA hydratase (ECH) and 3,2-trans-enoyl-CoA isomerase (ECI) a multifunctional enzyme where the N-terminal domain bears the hydratase/isomerase activities and the C-terminal domain the dehydrogenase activity. There are two mitochondrial enzymes: one which is monofunctional and the other which is, like its peroxisomal counterpart, multifunctional.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA) HCDH is part of a multifunctional enzyme which also contains an ECH/ECI domain as well as a 3-hydroxybutyryl-CoA epimerase domain .

The other proteins structurally related to HCDH are:

Bacterial 3-hydroxybutyryl-CoA dehydrogenase (

) which reduces 3-hydroxybutanoyl-CoA to acetoacetyl-CoA .

Eye lens protein lambda-crystallin , which is specific to lagomorphes (such as rabbit).

There are two major region of similarities in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the centre of the sequence.
D-amino acid oxidase, conserved site (D-amino_acid_oxidase_CS)
Type: Conserved_site

D-amino acid oxidase (

) (DAMOX or DAO) is an FAD flavoenzyme that catalyzes the oxidation of neutral and basic D-amino acids into their corresponding keto acids. DAOs have been characterised and sequenced in fungi and vertebrates where they are known to be located in the peroxisomes. D-aspartate oxidase (

) (DASOX) is an enzyme, structurally related to DAO, which catalyzes the same reaction but is active only toward dicarboxylic D-amino acids. In DAO, a conserved histidine has been shown to be important for the enzyme's catalytic activity.
Flagellar M-ring, N-terminal (FliF_N_dom)
Type: Domain

This domain is found at the N terminus of the flagellar M-ring protein FliF. It can also be found in YscJ lipoprotein, where it covers most of the sequence.

FliF is the major protein
of the M-ring in bacterial flagellar basal body .
The basal body consists of four rings (L,P,S and M) surrounding the
flagellar rod, which is believed to transmit motor rotation to the filament
.
The M ring is integral to the inner membrane of the cell, and may be
connected to the rod via the S (supramembrane) ring, which lies just distal
to it. The L and P rings reside in the outer membrane and periplasmic space,
respectively.
FliF lacks a signal peptide and is predicted to have considerable
α-helical structure, including an N-terminal sequence that is likely
to be membrane-spanning . Overall, however, FliF has a relatively
hydrophilic sequence, with a high charge density, especially towards its
C terminus .

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. These lipoproteins include the PrgK and SsaJ from Salmonella, MxiJ from Shigella, YscJ from Yersinia, and from the plant enteropathogens NolT (Rhizobium) and HrcJ (Erwinia).
6-phosphogluconate dehydrogenase (Pgluconate_DH)
Type: Family

This entry represents prokaryotic and eukaryotic 6PGD and a truncated prokaryotic 6PGD that lacks of a central region of about 140 residues, such as yqeC from Bacillus subtilis . Bacillus subtilis contains three classes of 6-phosphogluconate dehydrogenases (6PGD), including Gnd (YqjI), GntZ and YqeC. All of them are included in this entry. YgjiI is NADP+ dependent, while GntZ and YqeC are NAD+-dependent .
6-phosphogluconate-binding site (6PGdom_BS)
Type: Binding_site

6-Phosphogluconate dehydrogenase (

) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) . Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved . The protein is a homodimer in which the monomers act independently : each contains a large, mainly α-helical domain and a smaller β-α-β domain, containing a mixed parallel and anti-parallel 6-stranded β sheet . NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket .

This signature, found in the C-terminal all-alpha domain of 6-phosphogluconate dehydrogenase, contains the 6-phosphogluconate binding site. The NAD-binding domain is described in

.