SII-SWORD/CoKE huggingface dataset:
Sporulation initiation phosphotransferase B, C-terminal domain superfamily (Spo0B_C_sf)
Type: Homologous_superfamily

Response regulatory proteins such as sensor kinases control a variety of environmentally induced responses in bacteria. Sporulation initiation phosphotransferase B (Spo0B) is a response regulator that responds to nutritional stress by inducing sporulation. Spo0B is a phosphotransferase that acts upon stage 0 sporulation protein A (spo0A) using sporulation initiation phosphotransferase F (spo0F) as the phosphor-donor. Phosphorylated spo0A ca activate sporulation-specific gene transcription .

Spo0B has an α-β core structure that resembles the histidine kinase fold, but lacks the kinase ATP-binding site . This domain superfamily is found at the C terminus of spo0B, as well as in other sensor kinases.
Photosystem I reaction centre subunit PsaK (PSI_PsaK_bact)
Type: Homologous_superfamily

Photosystems I and II occur together in the same sets of organisms. Photosystem I uses light energy to transfer electrons from plastocyanin to ferredoxin, while photosystem II uses light energy to split water and releases molecular oxygen.

This entry represents Photosystem I reaction centre subunit PsaK from Cyanobacteria and Rhodophyta (red algae).
Tubulin/FtsZ-like, C-terminal domain (Tubulin/FtsZ-like_C)
Type: Homologous_superfamily

This domain superfamily is found in the tubulin alpha, beta and gamma chains, as well as the bacterial FtsZ family of proteins and other Tubulin-like proteins. These proteins are GTPases and are involved in polymer formation. Tubulin is the major component of microtubules, while FtsZ is the polymer-forming protein of bacterial cell division, it is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ can polymerise into tubes, sheets, and rings
in vitro
and is ubiquitous in bacteria and archaea. This is the C-terminal domain.
Annexin superfamily (Annexin_sf)
Type: Homologous_superfamily

The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner . The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) . Annexins are absent from yeasts and prokaryotes .

Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long . Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.

Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication .
Putative outer membrane protein superfamily (Put_OMP_sf)
Type: Homologous_superfamily

This entry contains proteins that have no known function.
TM1727-like, C-terminal domain superfamily (TM1727-like_C_sf)
Type: Homologous_superfamily

This presumed domain superfamily is found at the C terminus of a Rossmann-like domain suggesting that these proteins are oxidoreductases.
AMP nucleoside phosphorylase, N-terminal domain superfamily (AMP_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of bacterial AMP nucleoside phosphorylase (AMNp). The N- and C-termini form distinct domains which intertwine with each other to form a stable monomer which associates with five other monomers to yield the active hexamer. The N terminus consists of a long helix and a four-stranded sheet with a novel topology. The C terminus binds the nucleoside whereas the N terminus acts as the enzymatic regulatory domain. AMNp (

) catalyses the hydrolysis of AMP to form adenine and ribose 5-phosphate. thereby regulating intracellular AMP levels .
Beta-galactosidase, domain 2 superfamily (Betagal_dom2_sf)
Type: Homologous_superfamily

This entry represents the second domain of the five-domain beta-galactosidase enzyme that altogether catalyses the hydrolysis of beta(1-3) and beta(1-4) galactosyl bonds in oligosaccharides as well as the inverse reaction of enzymatic condensation and trans-glycosylation. This domain is made up of 16 antiparallel β-strands and an α-helix at its C terminus. The fold of this domain appears to be unique. In addition, the last seven strands of the domain form a subdomain with an immunoglobulin-like (I-type Ig) fold in which the first strand is divided between the two β-sheets. In penicillin spp this strand is interrupted by a 12-residue insertion which forms an additional edge-strand to the second β-sheet of the sub-domain. The remainder of the second domain forms a series of β-hairpins at its N terminus, four strands of which are contiguous with part of the Ig-like sub-domain, forming in total a seven-stranded antiparallel β-sheet.
Thrombin light chain domain superfamily (Thrombin_light_chain_sf)
Type: Homologous_superfamily

Thrombin is a Na+-activated, allosteric serine protease that functions in blood homeostasis, inflammation and wound healing . Thrombin (or coagulation factor II) is an enzyme that cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, and (in complex with thrombomodulin) protein C . Sodium binding is the major driving force behind the procoagulant, prothrombotic and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C . Prothrombin is activated on the surface of a phospholipid membrane where factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. This domain superfamily corresponds to the light chain of thrombin.
Pyruvate-flavodoxin oxidoreductase, EKR domain superfamily (Pyrv-flavodox_OxR_EKR_sf)
Type: Homologous_superfamily

EKR is a short, 33 residue, domain found in bacterial and some lower eukaryotic species which lies between a POR (pyruvate ferredoxin/flavodoxin oxidoreductase) domain (

) and the 4Fe-4S binding domain (

). It contains a characteristic EKR sequence motif. The exact function of this domain is not known.
Histone acetyl transferase 1, N-terminal domain superfamily (Hat1_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of the structure of histone acetyl transferase HAT1. It is often found in association with the C-terminal part of

. It seems to be motifs C and D of the structure. Histone acetyltransferases (HATs) catalyse the transfer of an acetyl group from acetyl-CoA to the lysine E-amino groups on the N-terminal tails of histones. HATs are involved in transcription since histones tend to be hyper-acetylated in actively transcribed regions of chromatin, whereas in transcriptionally silent regions histones are hypo-acetylated .
Rhodopsin, N-terminal domain superfamily (Rhodopsin_N_sf)
Type: Homologous_superfamily

Rhodopsin is the archetypal G-protein-coupled receptor. Such receptors participate in virtually all physiological processes as signalling molecules. They utilise heterotrimeric guanosine triphosphate (GTP)-binding proteins to transduce extracellular signals to intracellular events. Rhodopsin is important because of the pivotal role it plays in visual signal transduction. It is a dimeric transmembrane protein whose intradiskal surface consists of an N-terminal domain and three loops connecting six of the seven transmembrane helices. The N-terminal domain is a compact α-helical region with breaks and bends at proline residues outside the membrane . This entry represents the N-terminal domain superfamily, while the transmembrane region is represented by (

). The N-terminal domain is extracellular is and is necessary for successful dimerisation and molecular stability .
Sirohaem synthase, dimerisation domain superfamily (Sirohaem_synt_dimer_dom_sf)
Type: Homologous_superfamily

Bacterial sulphur metabolism depends on the iron-containing porphinoid sirohaem. CysG is a multi-functional enzyme with S-adenosyl-L-methionine (SAM)-dependent bismethyltransferase, dehydrogenase and ferrochelatase activities. CysG synthesizes sirohaem from uroporphyrinogen III via reactions which encompass two branchpoint intermediates in tetrapyrrole biosynthesis, diverting flux first from protoporphyrin IX biosynthesis and then from cobalamin (vitamin B12) biosynthesis. CysG is a dimer. Its dimerisation region is 74 residues long, and acts to hold the two structurally similar protomers held together asymmetrically through a number of salt-bridges across complementary residues within the dimerisation region . CysG dimerisation produces a series of active sites, accounting for CysG's multi-functionality, catalysing four diverse reactions:

Two SAM-dependent methylations

NAD+-dependent tetrapyrrole dehydrogenation

Metal chelation
Dihydroorotate dehydrogenase, electron transfer subunit, Fe-S binding domain superfamily (Dihydroorotate_DH_ele_sf)
Type: Homologous_superfamily

Lactococcus lactis is one of the few organisms with two dihydroorotate dehydrogenases (DHODs) A and B . The B enzyme is typical of DHODs in Gram-positive bacteria that use NAD+ as the second substrate. DHODB is a heterotetramer composed of a central homodimer of PyrDB subunits resembling the DHODA structure and two PyrK subunits along with three different cofactors: FMN, FAD, and a [2Fe-2S] cluster. The [2Fe-2S] iron-sulphur cluster binds to this C-terminal domain of the PyrK subunit, which is at the interface between the flavin and NAD binding domains and contains three β-strands. The four cysteine residues at the N-terminal part of this domain are the ones that bind, in pairs, to the iron-sulphur cluster. The conformation of the whole molecule means that the iron-sulphur cluster is localized in a well-ordered part of this domain close to the FAD binding site . The FAD and NAD binding domains are

and

respectively.
Valyl-tRNA synthetase, tRNA-binding arm superfamily (Val-tRNA_synth_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain superfamily of Valyl-tRNA synthetase, which consists of two helices in a long α-hairpin . This superfamily also matches ABC transporter, ATP-binding protein.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Haem oxygenase HugZ-like superfamily (Haem_oxidase_HugZ-like_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily that can be found in a group of putative haem-iron utilisation proteins, such as HugZ, a class of heme oxygenase that belongs to the PPOX family and lacks homology to the HmuO family. This enzyme releases iron during the conversion of heme to biliverdin .
Haem peroxidase domain superfamily, animal type (Haem_peroxidase_sf_animal)
Type: Homologous_superfamily

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions.

Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal haem peroxidases can be categorised as members of a superfamily: myeloperoxidase (MPO); eosinophil peroxidase (EPO); lactoperoxidase (LPO); thyroid peroxidase (TPO); prostaglandin H synthase (PGHS); and peroxidasin .
Large ribosomal subunit protein bL25, C-terminal (Ribosomal_bL25_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain, which has a mainly β-strand structure, found in the large ribosomal subunit protein bL25.

The bacterial large ribosomal subunit protein bL25, previously known as ribosomal protein L25, is bound to 5S rRNA along with uL5 and uL18, forming a separate domain of the ribosome . The solution structure of protein bL25 uncomplexed with RNA shows two significantly disordered loops and a closed β-barrel domain with a complex topology that has significant structural similarities to the N-terminal domain of the Thermus thermophilus ribosomal protein TL5, to the general stress protein CTC, and to the C-terminal anticodon-binding domain of Escherichia coli glutaminyl-tRNA synthetase (GlnRS) . GlnRS contains a duplication consisting of two L25-like β-barrels domains with the swapping of N-terminal strands.
Pleiotrophin/Midkine, N-terminal domain superfamily (PTN/MK_N_dom_sf)
Type: Homologous_superfamily

Several extracellular heparin-binding proteins involved in regulation of growth and differentiation belong to a new family of growth factors. These growth factors are highly related proteins of about 140 amino acids that contain 10 conserved cysteines probably involved in disulphide bonds, and include pleiotrophin (also known as heparin-binding growth-associated molecule HB-GAM, heparin-binding growth factor 8 HBGF-8, heparin-binding neutrophic factor HBNF and osteoblast specific protein OSF-1); midkine (MK) ; retinoic acid-induced heparin-binding protein (RIHB) ; and pleiotrophic factors alpha-1 and -2 and beta-1 and -2 from Xenopus laevis, the homologues of midkine and pleiotrophin respectively. Pleiotrophin is a heparin-binding protein that has neurotrophic activity and has mitogenic activity towards fibroblasts. It is highly expressed in brain and uterus tissues, but is also found in gut, muscle and skin. It is thought to possess an important brain-specific function. Midkine is a regulator of differentiation whose expression is regulated by retinoic acid, and, like pleiotrophin, is a heparin-binding growth/differentiation factor that acts on fibroblasts and nerve cells.

This entry represents the N-terminal domain superfamily of pleiotrophin and midkine .
Phosphoribosylglycinamide synthetase, C-domain superfamily (PRibGlycinamide_synth_C_sf)
Type: Homologous_superfamily

Phosphoribosylglycinamide synthetase (

) (GARS) (phosphoribosylamine glycine ligase) catalyses the second step in the
de novo
biosynthesis of purine. The reaction catalysed by phosphoribosylglycinamide synthetase is the ATP-dependent addition of 5-phosphoribosylamine to glycine to form 5'phosphoribosylglycinamide:

ATP + 5-phosphoribosylamine + glycine = ADP + P
i
+ 5'-phosphoribosylglycinamide

In bacteria, GARS is a monofunctional enzyme (encoded by the purD gene). In yeast, GARS is part of a bifunctional enzyme (encoded by the ADE5,7 gene) in conjunction with phosphoribosylformylglycinamidine cyclo-ligase (AIRS) . In higher eukaryotes, GARS is part of a trifunctional enzyme in conjunction with AIRS and with phosphoribosylglycinamide formyltransferase (GART), forming GARS-AIRS-GART .

This entry represents the C-domain superfamily of the phosphoribosylglycinamide synthetase, which is related to the C-terminal domain of biotin carboxylase/carbamoyl phosphate synthetase (

).
GroES chaperonin superfamily (Chaperonin_GroES_sf)
Type: Homologous_superfamily

The chaperonins are 'helper' molecules required for correct folding and subsequent assembly of some proteins . These are required for normal cell growth , and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10) .
Lipoprotein YajI-like superfamily (YajI-like_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily found in a group of bacterial lipoproteins, such as YajI from Escherichia coli or SadB from Salmonella typhimurium. SadB is required for proper surface expression of the autotransporter adhesin SadA .
PdaC/RsiV-like superfamily (PdaC/RsiV-like_sf)
Type: Homologous_superfamily

This entry represents a highly conserved domain superfamily found in a group of bacterial proteins. The function of this domain is not known. Proteins containing this domain include pdaC and anti-sigma-V factor RsiV from Bacillus subtilis. PdaC catalyzes the deacetylation of N-acetylmuramic acid (MurNAc) residues in peptidoglycan, a modification that confers resistance to lysosyme .
Quinolinate phosphoribosyl transferase, N-terminal domain superfamily (Quinolinate_PRibosylTase_N_sf)
Type: Homologous_superfamily

Quinolinate phosphoribosyl transferase (QPRTase) or nicotinate-nucleotide pyrophosphorylase

is involved in the
de novo
synthesis of NAD in both prokaryotes and eukaryotes. It catalyses the reaction of quinolinic acid with 5-phosphoribosyl-1-pyrophosphate (PRPP) in the presence of Mg
2+
to give rise to nicotinic acid mononucleotide (NaMN), pyrophosphate and carbon dioxide . Unlike

, this domain superfamily also includes the molybdenum transport system protein ModD.
XPA domain superfamily (XPA_sf)
Type: Homologous_superfamily

Xeroderma pigmentosum (XP) is a human autosomal recessive disease, characterised by a high incidence of sunlight-induced skin cancer. Skin cells of individual's with this condition are hypersensitive to ultraviolet light, due to defects in the incision step of DNA excision repair. There are a minimum of seven genetic complementation groups involved in this pathway: XP-A to XP-G. XP-A is the most severe form of the disease and is due to defects in a 30kDa nuclear protein called XPA (or XPAC) . The sequence of the XPA protein is conserved from higher eukaryotes to yeast (gene RAD14) . XPA is a hydrophilic protein of 247 to 296 amino-acid residues which has a C4-type zinc finger motif in its central section.

This superfamily represents a domain of the XPA protein.
Copper metallothionein superfamily (Cup1_sf)
Type: Homologous_superfamily

Metallothioneins are characterised by an abundance of cysteine residues and a lack of generic secondary structure motifs. This protein functions in primary metal storage, transport and detoxification . For the first 40 residues in the protein the polypeptide wraps around the metal by forming two large parallel loops separated by a deep cleft containing the metal cluster . This entry includes copper metallothioneins Cup1-1 and Cup1-2 from budding yeasts. They bind copper and mediate resistance to high concentrations of copper and cadmium .
Homeo-prospero domain superfamily (Homeo_prospero_dom_sf)
Type: Homologous_superfamily

This entry represents the homeo-prospero domain superfamily. This domain consists of a homeodomain-homology N-terminal region and the prospero-specific C-terminal region. The structure of these two regions consists of a single structural unit (a homeo-prospero domain), in which the prospero domain region is in position to contribute to DNA binding and also to mask a defined nuclear export signal that is within the putative homeodomain region. It is proposed that the homeo-prospero domain coordinately regulates prospero nuclear localisation and DNA binding specificity .

Prospero is a large Drosophila transcription factor protein that is expressed in all neural lineages of Drosophila embryos. It is needed for correct expression of several neural proteins and in determining the cell fates of neural stem cells. Homologues of prospero are found in a wide range of animals including humans with the highest level of similarity being found in the C-terminal 160 amino acids. This region was identified as containing an atypical homeobox domain followed by a prospero domain. However, the structure shows that these two regions form a single stable structural domain as defined here . This homeo-prospero domain binds to DNA.
Protein N-terminal glutamine amidohydrolase, alpha beta roll superfamily (N_Gln_amidohydro_ab_roll_sf)
Type: Homologous_superfamily

This entry represents a structural domain superfamily found in the N-terminal glutamine amidohydrolase (Nt
Q
-amidase) family of proteins. These proteins contain a region of approximately 200 residues carrying several distinctive motifs including a WDYHV motif and one of three cysteines. Protein N-terminal glutamine amidohydrolase is responsible for degradation of N-terminal glutamine .
Tetrahydrodipicolinate-N-succinyltransferase, N-terminal domain superfamily (THP_succinylTrfase_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of the enzyme tetrahydrodipicolinate-N-succinyltransferase .
DUF1653-like domain superfamily (DUF1653-like_dom_sf)
Type: Homologous_superfamily

This entry represents the structural domain superfamily found in DUF1653, a protein family of unknown function.