SII-SWORD/CoKE huggingface dataset:
Geminivirus C4 protein (Gemini_C4)
Type: Family

This family consists of the N-terminal region of geminivirus C4 or AC4 proteins. In Tomato yellow leaf curl virus the C4 protein is necessary for efficient spreading of the virus in Solanum lycopersicum (Tomato) (Lycopersicon esculentum) .
Glutamate synthase, alpha subunit, C-terminal (Glu_synth_asu_C)
Type: Domain

Glutamate synthase (GltS) is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channelling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation . GltS is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor. The active centres are synchronised to avoid the wasteful consumption of L-glutamine . There are three classes of GltS, which share many functional properties: bacterial NADPH-dependent GltS, ferredoxin-dependent GltS from photosynthetic cells, and NAD(P)H-dependent GltS from yeast, fungi and lower animals.

The dimeric alpha subunits each consist of four domains: N-terminal amidotransferase domain, the central domain, the FMN binding domain and the C-terminal domain. The C-terminal domain forms a right-handed β-helix that comprises seven helical turns . Each helical turn has a sharp bend that is associated with a repeated sequence motif consisting of G-XX-G-XXX-G. This domain does not contain any residues directly involved in catalysis, but has a crucial structural role.

This domain is also found in proteins such as subunit C of formylmethanofuran dehydrogenase, which catalyses the first step in methane formation from carbon dioxide in methanogenic archaea. There are two isoenzymes of formylmethanofuran dehydrogenase: a tungsten-containing isoenzyme (FwdC) and a molybdenum-containing isoenzyme (FmdC). The tungsten isoenzyme is constitutively transcribed, whereas transcription of the molybdenum operon is induced by molybdate .
V-type ATPase, V0 complex, 116kDa subunit family (V-ATPase_116kDa_su)
Type: Family

This entry represents the 116kDa subunit (or subunit a) found in the V0 complex of V-ATPases, respectively. The 116kDa subunit is a transmembrane glycoprotein required for the assembly and proton transport activity of the ATPase complex. Several isoforms of the 116kDa subunit exist, providing a potential role in the differential targeting and regulation of the V-ATPase for specific organelles .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
ABC transporter periplasmic binding domain (ABC_transptr_periplasmic_BD)
Type: Domain

ATP binding cassette (ABC) transporters are a ubiquitous family of importer and exporter proteins that consist of two α-helical transmembrane (TM) domains, which form a translocation pathway, and two cytoplasmic ABC domains, which power the transport reaction through binding and hydrolysis of ATP. In addition most bacterial importers employs a periplasmic substrate-binding protein (PBP) that delivers the ligand to the extracellular gate of the TM domains. These proteins bind their substrates selectively and with high affinity, which is thought to ensure the specificity of the transport reaction. Binding proteins in Gram-negative bacteria are present within the periplasm, whereas those in Gram-positive bacteria are tethered to the cell membrane via the acylation of a cysteine residue that is an integral component of a lipoprotein signal sequence. The cobalamin (vitamin B12) and the iron transport systems share many common attributes and probably evolved from the same origin .

The structure of the periplasmic-binding domain is composed of two subdomains, each consisting of a central β-sheet and surrounding α-helices, linked by a rigid α-helix. The substrate binding site is located in a cleft between the two α/β subdomains .

Some protein known to contain an iron siderophore/cobalamin periplasmic- binding domain are listed below:

Escherichia coli vitamin B12 transport protein btuF. It is the periplasmic binding protein for the vitamin B12 transporter btuCD.

Escherichia coli ferrichrome-binding periplasmic protein (fhuD). It binds iron(III)-hydroxamates.

Staphylococcus aureus ferric hydroxamate receptor 2 (fhuD2).

Escherichia coli ferrienterobactin-binding periplasmic protein fepB. It binds ferrienterobactin; part of the binding-protein-dependent transport system for uptake of ferrienterobactin.

Vibrio cholerae periplasmic binding protein (viuP).

Escherichia coli iron(III) dicitrate-binding periplasmic protein (fecB). It binds citrate-dependent iron(III); part of the binding-protein-dependent transport system for uptake of citrate-dependent iron(III).

Erwinia chrysanthemi achromobactin-binding periplasmic protein (cbrA). It binds citrate-or chloride-dependent iron(III); part of the binding-protein-dependent transport system cbrABCD for uptake of the siderophore achromobactin.

Yersinia pestis hemin-binding periplasmic protein (hmuT).
Transposase, Tc1-like (Transposase_Tc1-like)
Type: Domain

Transposase proteins are necessary for efficient DNA transposition. This helix-turn-helix (HTH) domain is found in the amino-terminal region of Tc1, Tc1A, Tc1B and Tc2B transposases of Caenorhabditis elegans . The region encompasses the specific DNA binding and second DNA recognition domains as well as an amino-terminal region of the catalytic domain of Tc3 as described in . Tc3 is a member of the Tc1/mariner family of transposable elements.
Herpesvirus UL25 (Herpes_UL25)
Type: Family

The herpes simplex virus 1 (HSV-1) UL25 is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA . It may function to stabilize capsids that contain full-length viral genomes
.
Keratin-associated protein (KAP)
Type: Family

Keratin-associated proteins (KAPs) are cysteine-rich proteins synthesized during the differentiation of hair matrix cells, and form hair
fibres in association with hair keratin intermediate filaments . This entry also includes the high-sulfur and high-tyrosine keratins from sheep and goats.

In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins, which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins . The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
Glycosyl transferase, family 8 (Glyco_trans_8)
Type: Family

This entry represents Glycosyltransferase family 8.

Glycosyltransferase family 8

comprises enzymes with a number of known activities; lipopolysaccharide galactosyltransferase (

), lipopolysaccharide glucosyltransferase 1 (

), glycogenin glucosyltransferase (

), inositol 1-α-galactosyltransferase (

), α-1,3-xylosyltransferase and β-1,3-glucuronyltransferase . These enzymes have a distant similarity to family GT_24.

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.
Phosphoribosyl-AMP cyclohydrolase domain (PRib_AMP_CycHydrolase_dom)
Type: Domain

The phosphoribosyl-AMP cyclohydrolase

catalyses the third step in the histidine (his) biosynthetic pathway:

5-phosphoribosyl-AMP H
2
O = 5-(5-phospho-D-ribosylaminoformimino)-1-(5-phospho-ribosyl) imidazole-4-carboxamide

It requires Zn
2
ions for activity .
Phosphatidylinositol-4-phosphate 4/5-kinase, core (PInositol-4-P-4/5-kinase_core)
Type: Domain

This entry represents a conserved region from the common kinase core found in the type I phosphatidylinositol-4-phosphate 4 and 5-kinases (PIP4K/PIP5K) family as described in . This region is found in I, II and III phosphatidylinositol-4-phosphate 5-kinases (PIP5K enzymes). PIP5K catalyses the formation of phosphoinositol-4,5-bisphosphate via the phosphorylation of phosphatidylinositol-4-phosphate a precursor in the phosphoinositide signalling pathway . This domain is also found in 1-phosphatidylinositol-3-phosphate 5-kinases, such as FAB1 from yeast and Drosophila , and FAB1A-D from Arabidopsis which catalyses the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 3,5-bisphosphate . FAB1C from Arabidopsis is predicted to act as a phosphatidylinositol-3P 5-kinase, but, because it lacks a FYVE domain, it is unlikely to be efficiently targeted to membranes containing the proposed phosphatidylinositol-3P substrate. Therefore, its molecular function remains unknown .
Major vault protein, N-terminal (Vault_N)
Type: Repeat

Vaults are the largest ribonucleoprotein particles known, having a mass of approximately 13 MDa. They are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction and may also play a role in nucleo-cytoplasmic transport. Vaults are present in most normal tissues, but are more highly expressed in epithelial cells with secretory and excretory functions, as well as in cells chronically exposed to xenobiotics, such as bronchial cells and cells lining the intestine . Overexpression of these proteins is linked with multidrug-resistance in cancer cells.

The mammalian vault structure is highly regular and consists of approximately 96 molecules of the 100kDa major vault protein (MVP), 2 molecules of the 240kDa minor vault protein TEP1, 8 molecules of the 193kDa minor vault protein VPARP and at least 6 copies of a small untranslated RNA of 88-141 bases. The MVP molecules form the core of the complex, which is a barrel-like structure with an invaginated waist and two protruding caps. The complex can unfold into two symmetrical flower-like structures with 8 petals each supposedly consisting of 6 MVP molecules .
Phosphoadenosine phosphosulphate reductase domain (PAPS_reduct_dom)
Type: Domain

This domain is found in phosphoadenosine phosphosulphate (PAPS) reductase enzymes or PAPS sulphotransferase. PAPS reductase is part of the adenine nucleotide alpha hydrolases superfamily also including N type ATP PPases and ATP sulphurylases .

A highly modified version of the P loop, the fingerprint peptide of mononucleotide-binding proteins, is present in the active site of the protein, which appears to be a positively charged cleft containing a number of conserved arginine and lysine residues. Although PAPS reductase has no ATPase activity, it shows a striking similarity to the structure of the ATP pyrophosphatase (ATP PPase) domain of GMP synthetase, indicating that both enzyme families have evolved from a common ancestral nucleotide-binding fold .

The enzyme uses thioredoxin as an electron donor for the reduction of PAPS to phospho-adenosine-phosphate (PAP) . It is also found in NodP nodulation protein P from Rhizobium meliloti (Sinorhizobium meliloti) which has ATP sulphurylase activity (sulphate adenylate transferase) .
Pseudouridine synthase II, N-terminal (PsdUridine_synth_N)
Type: Domain

This entry represents an N-terminal domain found in pseudouridine synthase TruB, as well as Cbf5p that modifies rRNA .

TruB is found in all domains of life and it is responsible for the pseudouridine residue present in the T loops of virtually all tRNAs. TruB recognises the preformed 3D structure of the T loop primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA .

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.
N-acetylmuramoyl-L-alanine amidase domain (Amidase_domain)
Type: Domain

Proteins containing this domain include zinc amidases that have N-acetylmuramoyl-L-alanine amidase activity

. This enzyme domain cleaves the amide bond between N-acetylmuramoyl and L-amino acids in bacterial cell walls (preferentially: D-lactyl-L-Ala). The bacteriophage endolysins PLY118 and PLY500 cleave between L-Ala and D-Glu residues of Listeria cell-wall peptidoglycan and are therefore peptidases (MEROPS subfamily M15C) . The structure is known for the Bacteriophage T7 structure and shows that two of the conserved histidines are zinc binding .
NAD kinase (NADK)
Type: Family

Members of this family are NAD kinases

. The enzymes catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates, as well as inorganic polyphosphate, as a source of phosphorus. Such enzymes are thus designated poly(P)/ATP-NAD kinases . NAD kinase is one of the key enzymes regulating the cellular NADP(H) level, and therefore NADPH-dependent reductive biosynthetic pathways .
Phosphate acetyl/butaryl transferase (PTA_PTB)
Type: Domain

This entry contains both phosphate acetyltransferase

:
Acetyl-CoA + phosphate = CoA + acetyl phosphate

and phosphate butaryltransferase

:
Butanoyl-CoA + phosphate = CoA + butanoyl phosphate

These enzymes catalyse the transfer of an acetyl or butaryl group to orthophosphate.
Hepatitis delta virus delta antigen (HDV_ag)
Type: Family

The Hepatitis delta virus (HDV) encodes a single protein, the hepatitis delta antigen (HDAg). The central region of this protein has been shown to bind RNA . Several interactions are also mediated by a coiled-coil region at the N terminus of the protein .
N-acetylmuramoyl-L-alanine amidase, catalytic domain (MurNAc-LAA_cat)
Type: Domain

N-acetylmuramoyl-L-alanine amidase or MurNAc-LAA (also known as peptidoglycan aminohydrolase, NAMLA amidase, NAMLAA, Amidase 3, and peptidoglycan amidase) is an autolysin that hydrolyzes the amide bond between N-acetylmuramoyl and L-amino acids in certain cell wall glycopeptides. These proteins are Zn-dependent peptidases with highly conserved residues involved in cation co-ordination.

In Escherichia coli, there are five MurNAc-LAAs present: AmiA, AmiB, AmiC and AmiD that are periplasmic, and AmpD that is cytoplasmic. Three of these (AmiA, AmiB and AmiC) belong to this family, the other two (AmiD and AmpD) do not. E. coli AmiA, AmiB and AmiC play an important role in cleaving the septum to release daughter cells after cell division . In general, bacterial MurNAc-LAAs are members of the bacterial autolytic system and carry a signal peptide in their N termini that allows their transport across the cytoplasmic membrane. However, the bacteriophage MurNAc-LAAs are endolysins since these phage-encoded enzymes break down bacterial peptidoglycan at the terminal stage of the phage reproduction cycle. As opposed to autolysins, almost all endolysins have no signal peptides and their translocation through the cytoplasmic membrane is thought to proceed with the help of phage-encoded holin proteins .

The amidase catalytic module is fused to another functional module (cell wall binding module) either at the N or C terminus, which is responsible for high affinity binding of the protein to the cell wall .
NodB homology domain (NODB_dom)
Type: Domain

The NodB homology domain is a catalytic domain of ~200 amino acid residues, which has been named after its similarity to rhizobial NodB chitooligosaccharide deacetylase. It is found in members of carbohydrate esterase family 4 (CE4) and in PuuE proteins.

Members of the CE4 family exhibit metal-dependent deacetylation of O- and N- acetylated polysaccharides, such as chitin, peptidoglycan, and acetylxylan. Proteins belonging to this family have conserved residues that are important for metal coordination (D-H-H triad) and enzymatic activity. CE4 enzymes typically require a divalent Zn(2+) or Ni(2+) metal ion that is usually coordinated by an aspartate and two histidine residues .

PuuE proteins are allantoinases that catalyse the hydrolytic cleavage of the hydantoin ring of allantoin. The conserved D-H-H metal-binding triad is replaced by E-H-W in PuuE proteins. Amino acid substitutions are also observed for residues that have been implicated in catalysis, conferring metal independency to the enzyme .

The NodB homology domain adopts a deformed (β/α) barrel fold comprising eight parallel β-strands, with the C-terminal ends of five of these strands forming the solvent-exposed active site region, surrounded by eight α-helices .
Metalloprotease TldD/E, N-terminal domain (Metalloprtase-TldD/E_N)
Type: Domain

This entry represents the N-terminal domain of TldD and TldE. This domain is also found at the N-terminal in uncharacterised archaeal proteins.

This entry includes a group of metalloproteases, such as TldD and TldE (also known as PmbA) from E. coli, which interact to form a heterodimeric metalloprotease. TldD and TldE were originally related to the biosynthesis of microcin B17 (MccB17), a peptide antibiotic produced by Escherichia coli strains carrying the pMccB17 plasmid that targets the DNA gyrase from sensitive bacteria. Later, they are shown to be metalloproteases involved in CcdA/CcdA41 degradation .
Geminivirus V2 protein (Gemini_V2)
Type: Family

Disruption of the V2 gene in Tomato yellow leaf curl virus (TYLCV) stopped its ability to systemically infect Solanum lycopersicum (Tomato) (Lycopersicon esculentum) plants, suggesting that the V2 gene product is required for successful infection of the host .
Rotavirus A/C, non-structural protein 5 (Rotavirus_A/C_NSP5)
Type: Family

Rotaviruses are dsRNA viruses that appear to infect a wide range of mammals. Gene 11 product is a non-structural phosphoprotein designated as NS26, now more commonly annotated as non-structural protein 5 (NSP5) .
Tn3 transposase DDE domain (Tn3_Tnp_DDE_dom)
Type: Domain

Proteins containing this domain include transposases of Tn3, Tn21, Tn1721, Tn2501, Tn3926 transposons from Escherichia coli. The specific binding of the Tn3 transposase to DNA has been demonstrated. Sequence analysis has suggested that the invariant triad of Asp689, Asp765, Glu895 (numbering as in Tn3) may correspond to the D-D-35-E motif previously implicated in the catalytic performance of numerous transposases .
Transposase IS3/IS911family (Transposase_8)
Type: Family

Transposase proteins are necessary for efficient DNA transposition. This family consists of various Escherichia coli insertion elements and other bacterial transposases some of which are members of the IS3 family. This region includes a helix-turn-helix motif (HTH) at the N terminus followed by a leucine zipper (LZ) motif. The LZ motif has been shown to mediate oligomerisation of the transposase components in IS911 .
Glycosyl transferase, family 11 (Glyco_trans_11)
Type: Family

Glycosyltransferase family 11

comprises enzymes with only one known activity; galactoside 2-L-fucosyltransferase (

).

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.
Tospovirus nucleocapsid protein (Tospo_nucleocap)
Type: Family

The tospovirus genome consists of three linear ssRNA segments, denoted L, M and S complexed with the nucleocapsid protein. The S RNA encodes the nucleocapsid protein and another non-structural protein .
Hepatitis C virus, Envelope glycoprotein E1 (HCV_Env)
Type: Domain

Poliovirus infection leads to drastic alterations in membrane permeability late during infection. Proteins 2B and 2BC enhance membrane permeability .
Adhesin lipoprotein (Lipoprotein_7)
Type: Family

This family includes the p50 and variable adherence-associated antigen
(Vaa) adhesins from Metamycoplasma hominis and some uncharacterised proteins from bacteria and archaea. M. hominis is a mycoplasma associated with human urogenital diseases, pneumonia, and septic
arthritis .
An adhesin is a cell surface molecule that mediates adhesion to other
cells or to the surrounding surface or substrate.
The Vaa antigen is a 50kDa surface lipoprotein that has four tandem
repetitive DNA sequences encoding a periodic peptide structure, and is
highly immunogenic in the human host . p50 is also a 50kDa
lipoprotein, having three repeats A,B and C, that may be a tetramer of
191kDa in its native environment .