SII-SWORD/CoKE huggingface dataset:
Beta-retroviral matrix superfamily (B_retro_matrix_sf)
Type: Homologous_superfamily

Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes . Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds which predominantly consist of four closely packed α-helices that are interconnected through loops, their primary sequences can be very different .

This entry represents matrix proteins from beta-retroviruses such as Mason-Pfizer monkey virus (MPMV) (Simian Mason-Pfizer virus) and Mouse mammary tumor virus (MMTV) . This entry also identifies matrix proteins from several eukaryotic endogenous retroviruses, which arise when one or more copies of the retroviral genome becomes integrated into the host genome .
HTHP domain superfamily (HTHP_sf)
Type: Homologous_superfamily

Hexameric tyrosine-coordinated heme protein (HTHP) is from the marine bacterium Silicibacter pomeroyi and has peroxidase and catalase activity. HTHP consists of six monomers which each binds a solvent accessible heme group and is stabilised by the interaction of three neighbouring monomers . The heme iron is penta-coordinated with a tyrosine residue as proximal ligand .
RAMP domain superfamily (RAMP_sf)
Type: Homologous_superfamily

The calcitonin-receptor-like receptor can function as either a calcitonin-gene-related peptide or an adrenomedullin receptor. The receptors function is modified by receptor activity modifying protein (RAMP). RAMPs are single-transmembrane-domain proteins .
Dinitrogenase iron-molybdenum cofactor, N-terminal domain superfamily (NafY_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain of the gamma (Y) subunit of nitrogenase, also known as nitrogenase accessory factor Y, NafY. This region is negatively charged and appears to be necessary for recognising and interacting with the apo state of dinitrogenase. The full-length NafY protein facilitates the transfer of iron-molybdenum cofactor (FeMo-co) into apodinitrogenase by binding to both. The C-terminal region (

), is the part that binds to the cofactor, and the N terminus binds to apodinitrogenase. Nitrogenase is the bacterial enzyme responsible for nitrogen fixation by catalysing the reduction of nitrogen gas (N2) to ammonium in an ATP-dependent manner. It has two components, dinitrogenase and dinitrogenase reductase .
Poly-gamma-glutamate hydrolase, zinc-binding motif superfamily (Gamma_PGA_hydro_sf)
Type: Homologous_superfamily

This superfamily is named after the most representative protein, Poly-gamma-glutamate hydrolase (PghP), a globular protein with an open α/β mixed core structure and a seven-stranded parallel/anti-parallel β-sheet. The β-sheet contains a core four-stranded parallel β-sheet. The structure includes a zinc-binding motif, His-Glu-His at the C-terminal end of the β-sheet and a catalytic centre containing a zinc ion and an overall topology resembling mammalian carboxypeptidase A and related enzymes .
Nanos domain superfamily (Nanos_sf)
Type: Homologous_superfamily

Nanos is a highly conserved RNA-binding protein in higher eukaryotes and functions as a key regulatory protein in translational control using a 3'untranslated region during the development and maintenance of germ cells. Nanos comprises a non-conserved amino-terminus and highly conserved carboxy-terminal regions. The C-terminal region has two conserved Cys-Cys-His-Cys (CCHC)-type zinc-finger motifs that are indispensable for nanos function .

The structure of the nanos-type zinc finger is composed of two independent zinc-finger (ZF) lobes, the N-terminal ZF1 and the C-terminal ZF2, which are connected by a linker helix . These lobes create a large cleft. Zinc ions in ZF1 and ZF2 are bound to the CCHC motif by tetrahedral coordination.
Pleiotrophin/Midkine, C-terminal domain superfamily (PTN/MK_C_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.

Pleiotrophin is structurally divided into two domains, both domains consisting of three antiparallel β-strands, but the C-terminal domain has a long flexible hairpin loop where a heparin-binding consensus sequence is located . This superfamily represents the C-terminal domain of pleiotrophin and midkine.
Protein PsiB-like superfamily (PsiB-like_sf)
Type: Homologous_superfamily

During F plasmid conjugation, the SOS response is suppressed by PsiB, an F-plasmid-encoded protein that binds and sequesters free RecA to prevent filament formation. PsiB contains a central five-stranded anti-parallel β sheet that is buttressed by α helices from the N and C termini. Its structure is similar to CapZ, a eukaryotic actin filament capping protein .
Vps16, C-terminal domain superfamily (Vps16_C_sf)
Type: Homologous_superfamily

Vps16 forms part of the Class C vacuolar protein sorting (Vps) complex. It is essential for vacuolar protein sorting, which is essential for viability in plants, but not yeast . The Class C Vps complex is required for SNARE-mediated membrane fusion at the lysosome-like yeast vacuole. It is thought to play essential roles in membrane docking and fusion at the Golgi-to-endosome and endosome-to-vacuole stages of transport . The role of VPS16 in this complex is not known.

The C-terminal domain of Vps16 binds to Vps33 for integration into the HOPS complex .
Ribonuclease III superfamily, archaeal (Ribo_III_sf_archaeal)
Type: Homologous_superfamily

This entry represents a domain superfamily of archaeal ribonuclease III proteins that consists of 5 α helices.
YihD-like superfamily (YihD_sf)
Type: Homologous_superfamily

This superfamily consists of several bacterial YihD proteins of unknown function .
Methylthiotransferase, N-terminal domain superfamily (Methylthiotransferase_N_sf)
Type: Homologous_superfamily

The methylthiotransferase (MTTase) or miaB-like family is named after the (dimethylallyl)adenosine tRNA MTTase miaB protein, which catalyses a C-H to C-S bond conversion in the methylthiolation of tRNA. A related bacterial enzyme rimO performs a similar methylthiolation, but on a protein substrate. RimO acts on the ribosomal protein uS12 and forms a separate MTTase subfamily. The miaB-subfamily includes mammalian CDK5 regulatory subunit-associated proteins and similar proteins in other eukaryotes. Two other subfamilies, yqeV and CDKAL1, are named after a Bacillus subtilis and a human protein, respectively. While yqeV-like proteins are found in bacteria, CDKAL1 subfamily members occur in eukaryotes and in archaebacteria. The likely MTTases from these 4 subfamilies contain an N-terminal MTTase domain, a central radical generating fold and a C-terminal TRAM domain (see

). The core forms a radical SAM fold (or AdoMet radical), containing a cysteine motif CxxxCxxC that binds a [4Fe-4S] cluster . A reducing equivalent from the [4Fe-4S]+ cluster is used to cleave S-adenosylmethionine (SAM) to generate methionine and a 5'-deoxyadenosyl radical. The latter is thought to produce a reactive substrate radical that is amenable to sulphur insertion . The N-terminal MTTase domain contains 3 cysteines that bind a second [4Fe-4S] cluster, in addition to the radical-generating [4Fe-4S] cluster, which could be involved in the thiolation reaction. The C-terminal TRAM domain is not shared with other radical SAM proteins outside the MTTase family. The TRAM domain can bind to RNA substrate and seems to be important for substrate recognition. The tertiary structure of the central radical SAM fold has six β/α motifs resembling a three-quarter TIM barrel core (see

) . The N-terminal MTTase domain might form an additional [β/α]2 TIM barrel unit .
CofD-like domain superfamily (CofD-like_dom_sf)
Type: Homologous_superfamily

This entry contains 2-phospho-L-lactate transferase (CofD), phosphoenolpyruvate transferase and related sequences. CofD catalyses the fourth step in the biosynthesis of coenzyme F420, which is the transfer of the 2-phospholactate moiety from lactyl (2) diphospho-(5') guanosine (LPPG) to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) with the formation of the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) and GMP. F420 is a flavin derivative found in methanogens, Mycobacteria, and several other lineages. This enzyme is characterised so far in Methanocaldococcus jannaschii (Methanococcus jannaschii) but appears restricted to F420-containing species and is predicted to carry out the same function in these other species. CofD monomer contains twelve β-strands, seven of them forming a Rossmann fold, and thirteen α-helices .
Excisionase-like superfamily (Excisionase-like_sf)
Type: Homologous_superfamily

The phage-encoded excisionase protein (Xis,

) is involved in excisive recombination by regulating the assembly of the excisive intasome and by inhibiting viral integration. It adopts an unusual winged-helix structure in which two α helices are packed against two extended strands. Also present in the structure is a two-stranded anti-parallel β-sheet, whose strands are connected by a four-residue wing. During interaction with DNA, helix alpha2 is thought to insert into the major groove, while the wing contacts the adjacent minor groove or phosphodiester backbone. The C-terminal region of Xis is involved in interaction with phage-encoded integrase (Int), and a putative C-terminal α helix may fold upon interaction with Int and/or DNA .
Phosphopantoate/pantothenate synthetase superfamily (PPS/PS_sf)
Type: Homologous_superfamily

Proteins in this superfamily include pantothenate synthetase (

) from Methanosarcina mazei and 4-phosphopantoate--beta-alanine ligase, also known as phosphopantothenate synthetase, (

) from Pyrococcus kodakaraensis. Pantothenate synthetase catalyses the condensation of pantoate with beta-alanine in an ATP-dependent and ADP-producing reaction . 4-phosphopantoate--beta-alanine ligase catalyses the conversion of (R)-4-phosphopantoate and beta-alanine to 4'-phosphopantothenate in the CoA biosynthesis pathway. It cannot use (R)-pantoate as substrate and thus does not display pantothenate synthetase (PS) activity .
NlpE, C-terminal domain superfamily (NlpE_C_sf)
Type: Homologous_superfamily

NlpE is a bacterial outer membrane lipoprotein that is necessary for signalling by the Cpx pathway . This pathway responds to cell envelope disturbances and increases the expression of periplasmic protein folding and degradation factors. While the molecular function of the NlpE protein is unknown, it may be involved in detecting bacterial adhesion to abiotic surfaces. In Escherichia coli and Salmonella typhi, NlpE is also known to confer copper tolerance in copper-sensitive strains of Escherichia coli, and may be involved in copper efflux and delivery of copper to copper-dependent enzymes .

NlpE consists of two β-barrel domains. The N-terminal domain resembles the bacterial lipocalin Blc, and the C-terminal domain has an oligonucleotide/oligosaccharide-binding (OB) fold .

This superfamily represents a domain is found at the C terminus of the NlpE protein.
DotD superfamily (DotD_sf)
Type: Homologous_superfamily

The DotD protein is a component of the Dot/Icm type IVB secretion system (T4BSS). The T4BSS core complex spans the inner and outer membranes. It is thought to be comprised of at least five proteins: DotC, DotD, DotF, DotG and DotH, with the latter being the outer membrane protein. DotD, together with DotC, is thought to be involved in the targeting of DotH .
YutD-like superfamily (YutD-like_sf)
Type: Homologous_superfamily

This superfamily contains a group of uncharacterised bacterial proteins, including YutD from Bacillus subtilis (PDBe:2kl5).
Cytochrome P460 superfamily (Cytochrome_P460_sp)
Type: Homologous_superfamily

This superfamily includes monoheme c-type cytochrome, cytochrome P460, from Nitrosomonas europea. It is a monoheme c-type cytochrome, a homodimeric structure with a predominantly β-sheet fold. The chromophore possesses unusual spectral properties analogous to those of the catalytic heme P460 of hydroxylamine oxidoreductase (HAO), the only known heme in biology to withdraw electrons from substrate coordinated to the iron .
NigD-like, C-terminal domain superfamily (NigD-like_C_dom_sf)
Type: Homologous_superfamily

This entry represents the C-terminal β-sandwich domain of NigD1 (BT_4005) from Bacteroides thetaiotaomicron and related proteins.

NigD1 is a protein encoded adjacent to genes required for biosynthesis and regulation of lipopolysaccharides (LPS) and phospholipids. This protein was shown to be involved in controlling outer membrane vesicles (OMV) production and act as a molecular switch for OMV biogenesis . NigD1 controls, via currently unknown mechanisms, the amount of LPS, proteins, and lipids allocated to OMVs .
Intracellular proteinase inhibitor (IPI)
Type: Homologous_superfamily

BsuPI from Bacillus subtilis is a member of this superfamily. It is an intracellular proteinase inhibitor (IPI) that has been suggested to regulate the major intracellular proteinase (ISP-1) activity in vivo . The structure of IPI is a variant of the all-beta, immunoglobulin (Ig) fold and adopts a β barrel topology.
EAGR domain superfamily (EAGR_sf)
Type: Homologous_superfamily

The EAGR box, Enriched in Aromatic and Glycine Residues, is found in three different proteins of the Mycoplasma genitalium terminal organelle, which acts in both cytadherence and gliding motility. The presence of this domain in a genome predicts the Mycoplasma-type terminal organelle structure, gliding motility, and cytadherence . The EAGR box may occur from one to nine times in a protein.
Bacteriophage 933W-like, putative excisionase superfamily (933W_put_Xis_sf)
Type: Homologous_superfamily

This domain superfamily consists of several putative phage and prophage excisionase proteins of around 80 residues in length.
Cox superfamily (Cox_sf)
Type: Homologous_superfamily

Cox proteins are expressed by Enterobacteria phages. The Cox protein is a 79-residue basic protein with a predicted strong helix-turn-helix DNA-binding motif. It inhibits integrative recombination and it activates site-specific excision of the HP1 genome from the Haemophilus influenzae chromosome, Hp1. Cox appears to function as a tetramer. Cox binding sites consist of two direct repeats of the consensus motif 5'-GGTMAWWWWA, one Cox tetramer binding to each motif. Cox binding interferes with the interaction of HP1 integrase with one of its binding sites, IBS5. This competition is central to directional control. Both Cox binding sites are needed for full inhibition of integration and for activating excision, because it plays a positive role in assembling the nucleoprotein complexes that produce excisive recombination, by inducing the formation of a critical conformation in those complexes .
Transposon Tn1545/Tn916, excisionase (Tn1545/Tn916_Xis)
Type: Homologous_superfamily

This superfamily includes excisionases from transposon Tn1545 and Tn916.

The phage-encoded excisionase protein Tn916-Xis adopts a winged-helix structure that consists of a three-stranded anti-parallel β-sheet that packs against a helix-turn-helix (HTH) motif and a third C-terminal α-helix. It is encoded for by Tn916, which also codes for the integrase Tn916-Int. The protein interacts with DNA by the insertion of helix α2 into the major groove and the contact of the hairpin that connects strands β2 and β3 with the adjacent phosphodiester backbone and/or minor groove. Tn916-Xis stimulates phage excision and inhibits viral integration by stabilising distorted DNA structures .
Scaffold protein B superfamily (Phage_B_sf)
Type: Homologous_superfamily

This is a superfamily of proteins from single-stranded DNA bacteriophages. Scaffold proteins B and D are required for procapsid formation. Sixty copies of the internal scaffold protein B are found in the procapsid .
Protein CHLORORESPIRATORY REDUCTION 7-like superfamily (CRR7-like_sf)
Type: Homologous_superfamily

This entry includes protein from cyanobacteria, blue-green algae and plants, including CRR7 (Chlororespiratory reduction 7) protein from Arabidopsis. CRR7 is part of the chloroplastic NAD(P)H dehydrogenase complex (NDH Complex) involved in respiration, photosystem I (PSI) cyclic electron transport and CO2 uptake . It is likely to be involved in the final step of the formation of the NDH Complex, in which its intermediate is inserted into thylakoids .
Small outer capsid protein superfamily (Soc_sf)
Type: Homologous_superfamily

Small outer capsid protein stabilises T4 capsids after the majority of the capsid assembly stages, and helps to stabilise T4 against high temperatures and pH extremes by binding the capsid surface at interfaces between Gp23 hexameric capsomers .

This superfamily consists of 2 α helices and 6 β strands .
Carbamoyltransferase, C-terminal domain superfamily (Carbam_trans_C_sf)
Type: Homologous_superfamily

This domain superfamily is found in NodU from Rhizobium, CmcH from Nocardia lactamdurans and the bifunctional carbamoyltransferase TobZ from Streptoalloteichus tenebrarius. NodU, a Rhizobium protein involved in the synthesis of nodulation factors, has 6-O-carbamoyltransferase-like activity . CmcH is involved in cephamycin (antibiotic) biosynthesis and has 3-hydroxymethylcephem carbamoyltransferase activity (

). TobZ functions as an ATP carbamoyltransferase and tobramycin carbamoyltransferase . This entry represents the C-terminal domain superfamily.
dTDP-4-dehydro-6-deoxy-alpha-D-glucopyranose 2,3-dehydratase superfamily (EvaA-like_sf)
Type: Homologous_superfamily

This domain superfamily occurs in a range of proteins from antibiotic production pathways. These include the gra-ORF27

product that probably functions at an early step, most likely as a dTDP-4-keto-6- deoxyglucose-2,3-dehydratase . Its homologues include dnmT from the daunorubicin biosynthetic gene cluster in S. peucetius , a similar gene from the daunomycin biosynthetic cluster in Streptomyces sp. (strain 5)

, eryBVI from the erythromycin cluster in S. erythraea and snoH from the nogalamycin cluster in S. nogalater. This domain is a 200 amino acid long region, which may be a structural unit, that occurs twice within the proteins that contain it.

This entry also includes sugar 2,3-dehydratase, EvaA, that belongs to the "Nudix" hydrolase family, members of which often function as "housekeeping" enzymes. EvaA is organised as a dimer, each subunit of the dimer folds into two domains, which are related by a 2-fold rotational axis and which arose via gene duplication. Two binding sites for the dTDP-sugar ligands, pockets A and B, have been identified in each subunit. Site-directed mutagenesis experiments and activity assays strongly suggest that pocket A represents the active site and pocket B is a vestige of the gene duplication event .
Arterivirus papain-like cysteine protease beta (PCPbeta) domain superfamily (AV_PCPbeta_sf)
Type: Homologous_superfamily

Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries:

Equine arteritis virus (EAV).

Porcine reproductive and respiratory syndrome virus (PRRSV).

Mice actate dehydrogenase-elevating virus.

Simian hemorrhagic fever virus.

The arterivirus replicase gene is composed of two open reading frames (ORFs). ORF1a is translated directly from the genomic RNA, whereas ORF1b can be expressed only by ribosomal frameshifting, yelding a 1ab fusion protein. Both replicase gene products are multidomain precursor proteins which are proteolytically processed into functional nonstructural proteins (nsps) by a complex proteolytic cascade that is directed by four (PRRSV/LDV) or three (EAV) proteinase domains encoded in ORF1a. The arterivirus replicase processing scheme involves the rapid autoproteolytic release of two or three N-terminal nsps (nsp1 (or nsp1alpha/1beta) and nsp2) and the subsequent processing of the remaining polyproteins by the "main protease" residing in nsp4, together resulting in a set of 13 or 14 individual nsps. The arterivirus nsp1 region contains a tandem of papain-like cysteine autoprotease domains (PCPalpha and PCPbeta), but in EAV PCPalpha has lost its enzymatic activity, resulting in the 'merge' of nsp1alpha and nsp1beta into a single nsp1 subunit. Thus, instead of three self-cleaving N-terminal subunits, EAV has two: nsp1 and nsp2. The PCPalpha and PCPbeta domains mediate the nsp1alpha|1beta and nsp1beta|2 cleavages, respectively. The catalytic dyad of PCPalpha and PCPbeta domains is composed of Cys and His residues. In EAV, a Lys residue is found in place of the catalytic Cys residue, which explains the proteolytic deficiency of the EAV PCPalpha domain . The PCPalpha and PCPbeta domains form respectively peptidase families C31 and C32.

The PCPalpha and PCPbeta domains have a typical papain fold, which consists of a compact global region containing sequentially connected left (L) and right (R) parts in a so-called standard orientation. The L subdomain of PCPalpha consists of four α-helices, while the R subdomain is formed by three antiparallel β strands . The L subdomain of the PCBbeta consists of three α-helices, while the R subdomain is formed by four antiparallel β-strands . The Cys and His residues face each other at the L-R interface and form the catalytic centre of the PCPalpha and PCPbeta domains .

This entry represents the PCPbeta domain (peptidase C32) superfamily.