SII-SWORD/CoKE huggingface dataset:
Gas vesicle protein GvpA-like (Gas-vesicle_GvpA-like)
Type: Family

Gas vesicles (GVs) are small, hollow, gas filled protein structures found in several cyanobacterial and archaebacterial microorganisms . They allow the positioning of the bacteria at the favourable depth for growth. Gas vesicles are hollow cylindrical tubes, closed by a hollow, conical cap at each end. Both the conical end caps and central cylinder are made up of 4-5 nm wide ribs that run at right angles to the long axis of the structure. Gas vesicles seem to be constituted of two different protein components, GvpA and GvpC. GvpA, a small protein of about 70 amino acid residues, is the main constituent of gas vesicles and form the essential core of the structure, while GvpC binds the exterior of the GV and provides additional structural reinforcement . The sequence of GVPa is extremely well conserved. GvpJ and GvpM, two proteins encoded in the cluster of genes required for gas vesicle synthesis in the archaebacteria Halobacterium salinarum and Halobacterium mediterranei (Haloferax mediterranei), have been found to be evolutionary related to GVPa. The exact function of these two proteins is not known, although they could be important for determining the shape determination gas vesicles. The N-terminal domain of Aphanizomenon flos-aquae protein GvpA/J is also related to GvpA.
Epoxide hydrolase-like (Epox_hydrolase-like)
Type: Family

The α/β hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogenetic
origin and catalytic function. The core of each enzyme is an α/β-sheet (rather than a barrel), containing
8 strands connected by helices . The enzymes are believed to have diverged from a common ancestor,
preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne
on loops, which are the best conserved structural features of the fold. The epoxide hydrolases (EH) add water to
epoxides, forming the corresponding diol. On the basis of sequence similarity, it has been proposed that the
mammalian soluble EHs contain 2 evolutionarily distinct domains, the N-terminal domain is similar to bacterial
haloacid dehalogenase, while the C-terminal domain is similar to soluble plant EH, microsomal EH, and bacterial
haloalkane dehalogenase (HLD) . The mechanism of HLD, established by X-ray crystallographic analysis
of an HDL-substrate intermediate , involves nucleophilic attack of Asp-124 on the halogen-substituted
terminal carbon of the substrate, forming a covalently-bound ester intermediate. The Asp-260/His-289 pair
activate a water molecule that hydrolyses the ester intermediate to release the product. The similarity of EH to
HLD is important for deducing a catalytic mechanism for EH. Mutagenesis experiments on murine soluble EH
confirmed the crucial role of nucleophile Asp-333 and His-523 in the catalytic mechanism and the importance of
conserved His-263 and His-332 .
Elongation factor EFG, domain V-like (EFG_V-like)
Type: Domain

Elongation factor 2 (EF2 or EFG) is folded into five domains, with domains I and II forming the N-terminal block, domains IV and V forming the C-terminal block, and domain III providing the covalently-linked flexible connection between the two . This entry represents the domain V of EF2 of both prokaryotes and eukaryotes (also known as eEF2). This domain is also found in elongation factor 4 and some tetracycline resistance proteins and adopts a ferredoxin-like fold .
CbxX/CfxQ (CbxX/CfxQ)
Type: Family

The Cfx genes in Ralstonia eutropha (Alcaligenes eutrophus) encode a number of Calvin cycle enzymes. The observed sizes of two of the gene products, CfxX and CfxY, are 35kDa and 27kDa respectively . No functions could be assigned to CfxX and CfxY, but CfxQ is required for the expression of rubisco. These proteins show a high degree of similarity to the Bacillus subtilis stage V sporulation protein K .
Peptidase M41 (Peptidase_M41)
Type: Domain

This group of metallopeptidases belong to MEROPS peptidase family M41 (FtsH endopeptidase family, clan MA(E)). The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH.

The peptidase M41 family belong to a larger family of zinc metalloproteases. This family includes the cell division protein FtsH, and the yeast mitochondrial respiratory chain complexes assembly protein, which is a putative ATP-dependent protease required for assembly of the mitochondrial respiratory chain and ATPase complexes. FtsH is an integral membrane protein, which seems to act as an ATP-dependent zinc metallopeptidase that binds one zinc ion.

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

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

Iodothyronine deiodinase (

) (DI) is the vertebrate enzyme responsible for the deiodination of the prohormone thyroxine (T4 or 3,5,3',5'-tetraiodothyronine) into the biologically active hormone T3 (3,5,3'-triiodothyronine) and of T3 into the inactive metabolite T2 (3,3'-diiodothyronine). All known DI are proteins of about 250 residues that contain a selenocysteine at their active site. Three types of DI are known, type I is commonly found in the liver and kidney , type II is essential for providing the brain with the appropriate levels of T3 during the critical period of development, and type III (also known as thyroxine 5-deiodinase) is essential for the regulation of thyroid hormone inactivation during embryological development.
CBS domain (CBS_dom)
Type: Domain

CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain . CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids . Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases . CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet . CBS domain pairs from AMPK bind AMP or ATP . The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis .
Type II secretion system protein GspN, conserved site (T2SS_GspN_CS)
Type: Conserved_site

GspN is a cytoplasmic membrane component of the type II secretion system (T2SS). It is present in T2SS operons of a subset of Gram-negative speciesI, such as Aeromonas hydrophila (gene exeN); Erwinia carotovora (gene outN); Klebsiella pneumoniae (gene pulN); or Vibrio cholerae (gene epsN) . The size of the 'N' protein is around 250 amino acids. It apparently contains a single transmembrane domain located in the N-terminal section. The short N-terminal domain is
predicted to be cytoplasmic and the large C-terminal domain periplasmic.

This entry represents a conserved site found towards the N terminus of bacterial type II secretion system protein GspN.
Pre-hexon-linking protein VIII (Adeno_PVIII)
Type: Family

This family includes the minor capsid protein VIII from adenoviruses. Protein VIII is a structural component of the virion that lashes peripentonal hexons to the hexons situated in the facets through its interaction with the capsid vertex protein . Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised .
CTF transcription factor/nuclear factor 1 (CTF/NFI)
Type: Family

Nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF) (also known as TGGCA-binding proteins) are a family of vertebrate nuclear proteins which recognise and bind, as dimers, the palindromic DNA sequence 5'-TGGCANNNTGCCA-3'. This family was first described for its role in stimulating the initiation of adenovirus DNA replication . In vertebrates there are four members NFIA, NFIB, NFIC, and NFIX and an orthologue from Caenorhabditis elegans has been described, called Nuclear factor I family protein (NFI-I) . The CTF/NF-I proteins are individually capable of activating transcription and DNA replication, thus they function by regulating cell proliferation and differentiation. They are involved in normal development and have been associated with developmental abnormalities and cancer in humans . In a given species, there are a large number of different CTF/NF-I proteins, generated both by alternative splicing and by the occurrence of four different genes. CTF/NF-1 proteins contain 400 to 600 amino acids. The N-terminal 200 amino-acid sequence, almost perfectly conserved in all species and genes sequenced, mediates site-specific DNA recognition, protein dimerisation and Adenovirus DNA replication. The C-terminal 100 amino acids contain the transcriptional activation domain. This activation domain is the target of gene expression regulatory pathways elicited by growth factors and it interacts with basal transcription factors and with histone H3 .
Oxysterol-binding protein (Oxysterol-bd)
Type: Family

A number of eukaryotic proteins that seem to be involved with sterol synthesis and/or its regulation have been found to be evolutionary related. These include mammalian oxysterol-binding protein (OSBP), a protein of about 800 amino-acid residues that binds a variety of oxysterols (oxygenated derivatives of cholesterol) ; yeast Osh1, a protein of 859 residues that also plays a role in ergosterol synthesis ; yeast proteins Hes1 and Kes1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis ; Probable transporter efuK from the fungi Hormonema carpetanum, which is involved in the biosynthesis of enfumafungin ; and OSBP-related proteins (ORP) from plants such as Arabidopsis thaliana .
Initiation factor 2B-related (IF-2B-related)
Type: Family

Initiation factor 2 binds to Met-tRNA, GTP and the small ribosomal subunit. The eukaryotic translation initiation factor EIF-2B is a complex made up of five different subunits, alpha, beta, gamma, delta and epsilon, and catalyses the exchange of EIF-2-bound GDP for GTP. This family includes initiation factor 2B alpha, beta and delta subunits from eukaryotes; related proteins from archaebacteria and IF-2 from prokaryotes and also contains a subfamily of proteins in eukaryotes, archaeae (e.g. Pyrococcus furiosus), or eubacteria such as Bacillus subtilis and Thermotoga maritima. Many of these proteins were initially annotated as putative translation initiation factors despite the fact that there is no evidence for the requirement of an IF2 recycling factor in prokaryotic translation initiation. Recently, one of these proteins from B. subtilis has been functionally characterised as a 5-methylthioribose-1-phosphate isomerase (MTNA) . This enzyme participates in the methionine salvage pathway catalysing the isomerisation of 5-methylthioribose-1-phosphate to 5-methylthioribulose-1-phosphate . The methionine salvage pathway leads to the synthesis of methionine from methylthioadenosine, the end product of the spermidine and spermine anabolism in many species.
Geminivirus AR1 coat protein (Gem_coat_AR1)
Type: Family

Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name . Most geminiviruses can be divided into two subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted African cassava mosaic virus, Tomato golden mosaic virus (TGMV) and Bean golden mosaic virus (BGMV) possess a bipartite genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted Maize streak virus (MSV) and Wheat dwarf virus (WDV) . Beet curly top virus (BCTV), and Tobacco yellow dwarf virus belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by a specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous plants.

Sequence comparison of the whitefly-transmitted Squash leaf curl virus (SqLCV) and Tomato yellow leaf curl virus (TYLCV) with the genomic components of TGMV and BGMV reveals a close evolutionary relationship . Amino acid sequence alignments of Potato yellow mosaic virus (PYMV) proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated from the New World, especially in the putative coat protein gene regions . Comparison of MSV DNA-encoded proteins with those of other geminiviruses infecting monocotyledonous plants, including Panicum streak virus and Miscanthus streak virus (MiSV) , reveal high levels of similarity.
Ras-like guanine nucleotide exchange factor, N-terminal (Ras-like_Gua-exchang_fac_N)
Type: Domain

The N-terminal domain of guanine nucleotide exchange factor (GEF) for Ras-like GTPases is also called REM domain (Ras exchanger motif). REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few .

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved . The structure consists of two distinct α helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.

This entry represents a domain found in several GEF for Ras-like small GTPases which lies N-terminal to the RasGef (Cdc25-like) domain.
Triosephosphate isomerase (Triosephosphate_isomerase)
Type: Family

Triosephosphate isomerase (

) (TIM) is the glycolytic enzyme that catalyses the reversible interconversion of glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. TIM plays an important role in several metabolic pathways and is essential for efficient energy production, highly conserved in prokaryotes and eukaryotes. In pathogenic organisms, this enzyme plays a crucial role obtaining energy for infection and survival. TIM is a dimer of identical subunits, each of which is made up of about 250 amino-acid residues. A glutamic acid residue is involved in the catalytic mechanism .

The tertiary structure of TIM has eight β/α motifs folded into a barrel structure. The TIM barrel fold occurs ubiquitously and is found in numerous other enzymes that can be involved in energy metabolism, macromolecule metabolism, or small molecule metabolism .

The sequence around the active site residue is perfectly conserved in all known TIM's. Deficiencies in TIM are associated with haemolytic anaemia coupled with a progressive, severe neurological disorder .
DegT/DnrJ/EryC1/StrS aminotransferase (DegT/StrS_aminotransferase)
Type: Family

This entry represents the 3-amino-5-hydroxybenzoic acid synthase family (AHBA_syn) that are probably all pyridoxal-phosphate-dependent aminotransferase enzymes with a variety of molecular functions. Members of the family have the same structural fold as members of the pyridoxal phosphate (PLP)-dependent aspartate aminotransferase superfamily .

The AHBA_syn family members are involved in various biosynthetic pathways for secondary metabolites. The AHBA_synfamily includes StsA

, StsC

and StsS . The aminotransferase activity was demonstrated for purified StsC protein as the L-glutamine:scyllo-inosose aminotransferase

, which catalyses the first amino transfer in the biosynthesis of the streptidine subunit of streptomycin . Some other well studied proteins in this family are AHBA_synthase, the protein product of the pleiotropic regulatory gene degT, Arnb aminotransferase and pilin glycosylation protein. The prototype of this family, the AHBA_synthase, is a dimeric PLP dependent enzyme.

AHBA_syn is the terminal enzyme of 3-amino-5-hydroxybenzoic acid (AHBA) formation, which is involved in the biosynthesis of ansamycin antibiotics, including rifamycin B. Some members of this family are involved in 4-amino-6-deoxy-monosaccharide D-perosamine synthesis. Perosamine is an important element in the glycosylation of several cell products, such as antibiotics and lipopolysaccharides of Gram-positive and Gram-negative bacteria. The pilin glycosylation protein encoded by gene pglA, is a galactosyltransferase involved in pilin glycosylation. Additionally, this family consists of ArnB (PmrH) aminotransferase, a 4-amino-4-deoxy-L-arabinose lipopolysaccharide-modifying enzyme. This family also includes several predicted pyridoxal phosphate-dependent enzymes apparently involved in regulation of cell wall biogenesis. The catalytic lysine which is present in all characterised PLP dependent enzymes is replaced by histidine in some members of this family .
Regulatory protein cro-like (Cro-like)
Type: Family

Bacteriophage lambda encodes two repressors: the Cro repressor that acts to turn off early gene transcription during the lytic cycle, and the lambda or cI repressor that is required to maintain lysogenic growth. Together the Cro and cI repressors form a helix-turn-helix (HTH) superfamily. The lambda Cro repressor binds to DNA as a highly flexible dimer. The crystal structure of the lambda Cro repressor reveals a HTH DNA-binding protein with an α/β fold that differs from other Cro family members, possibly by an evolutionary fold change . Most Cro proteins, such as Enterobacteria phage P22 Cro and Bacteriophage 434 Cro, have an all-α structure that is thought to be ancestral to lambda Cro, where the fourth and fifth helices are replaced by a β-sheet, possibly as a result of secondary structure switching rather than by nonhomologous replacement . This entry represents the lambda-type Cro repressor with an α/β topology found in tailed bacteriophages and prophages mainly from proteobacteria.
Geminivirus AL3 coat protein (Gemini_AL3)
Type: Family

Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name . Most geminiviruses can be divided into two subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted African cassava mosaic virus, Tomato golden mosaic virus (TGMV) and Bean golden mosaic virus (BGMV) possess a bipartite genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted Maize streak virus (MSV) and Wheat dwarf virus (WDV) . Beet curly top virus (BCTV), and Tobacco yellow dwarf virus belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by a specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous plants.

Sequence comparison of the whitefly-transmitted Squash leaf curl virus (SqLCV) and Tomato yellow leaf curl virus (TYLCV) with the genomic components of TGMV and BGMV reveals a close evolutionary relationship . Amino acid sequence alignments of Potato yellow mosaic virus (PYMV) proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated from the New World, especially in the putative coat protein gene regions . Comparison of MSV DNA-encoded proteins with those of other geminiviruses infecting monocotyledonous plants, including Panicum streak virus and Miscanthus streak virus (MiSV) , reveal high levels of similarity.

Geminiviruses contain three ORFs (designated AL1, AL2, and AL3) that overlap and are specified by multiple polycistronic mRNAs. The AL3 protein comprises approximately 0.05% of the cellular proteins and is present in the soluble and organelle fractions . AL3 may form oligomers . Immunoprecipitation of AL3 in a baculovirus expression system extracts expressing both AL1 and AL3 showed that the two proteins also complex with each other. The AL3 protein is involved in viral replication.
Pyridoxamine 5'-phosphate oxidase (Pyridox_Oxase)
Type: Family

Pyridoxamine 5'-phosphate oxidase (

) is an enzyme that is involved in the de novo synthesis of pyridoxine (vitamin B6) and pyridoxal phosphate. It oxidizes pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P. The enzyme requires the presence of flavin mononucleotide (FMN) as a cofactor, although there is some evidence that coenzyme F420 may perform this role in some species .

The sequences of the enzyme from bacterial (genes pdxH or fprA) and fungal (gene PDX3) sources show that this protein has been highly conserved throughout evolution. PdxH is evolutionary related to one of the enzymes in the phenazine biosynthesis protein pathway, phzD (also known as phzG) .
Capsid protein VP1,Polyomavirus (Capsid_VP1_Polyomavir)
Type: Family

This entry represents the major capsid protein VP1 (viral protein 1) from Polyomaviruses, such as Murine polyomavirus (strain P16 small-plaque) (MPyV) . Polyomaviruses are dsDNA viruses with no RNA stage in their life cycle. The virus capsid is composed of 72 icosahedral units, each of which is composed of five copies of VP1. The virus attaches to the cell surface by recognition of oligosaccharides terminating in alpha(2,3)-linked sialic acid. The capsid protein VP1 forms a pentamer. The complete capsid is composed of 72 VP1 pentamers, with a minor capsid protein, VP2 or VP3, inserted into the centre of each pentamer like a hairpin. This structure restricts the exposure of internal proteins during viral entry. Polyomavirus coat assembly is rigorously controlled by chaperone-mediated assembly. During viral infection, the heat shock chaperone hsc70 binds VP1 and co-localises it in the nucleus, thereby regulating capsid assembly .