SII-SWORD/CoKE huggingface dataset:
TLV/ENV coat polyprotein (TLV/ENV_coat_polyprotein)
Type: Family

Enveloped viruses such as Human immunodeficiency virus 1, influenza virus, and Ebola virus sp. express a surface glycoprotein that mediates both cell attachment and fusion of viral and cellular membranes. The ENV polyprotein (coat polyprotein) usually contains two coat proteins which differ depending on the source.

The structure of a number of the ENV polyprotein domains have been determined:

The crystal structure of an extraviral segment of the Moloney murine leukemia virus (MoMuLV) transmembrane (TM) subunit has been determined to 1.7-A resolution. This segment contains a trimeric coiled coil, with a hydrophobic cluster at its base and a strand that packs in an antiparallel orientation against the coiled coil. This structure serves as a model for a wide range of viral fusion proteins; key residues in this structure are conserved among C- and D-type retroviruses and the filovirus ebola .

An essential step in retrovirus infection is the binding of the virus to its receptor on a target cell. The structure of the receptor-binding domain of the envelope glycoprotein from Friend murine leukemia virus (F-MuLV) has been determined determined to 2.0-A resolution. The core of the domain is an antiparallel β sandwich, with two interstrand loops forming a helical subdomain atop the sandwich. The residues in the helical region, but not in the β sandwich, are highly variable among mammalian C-type retroviruses with distinct tropisms, indicating that the helical subdomain determines the receptor specificity of the virus .
Hyaluronidase (Hyaluronidase)
Type: Family

Glycoside hydrolase family 56

comprises enzymes with only one known activity; hyaluronidase

.

The venom of Apis mellifera (Honeybee) contains several biologically-active peptides and two enzymes, one of which is a hyaluronidase . The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four cysteines and a number of potential glycosylation sites . The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation .

PH-20 is required for sperm adhesion to the egg zona pellucida; it is located on both the sperm plasma membrane and acrosomal membrane . The amino acid sequence of the mature protein contains 468 amino acids, and includes six potential N-linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the C terminus .

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Spectrin/alpha-actinin (Spectrin/alpha-actinin)
Type: Repeat

Spectrin repeats are found in several proteins involved in cytoskeletal structure and in proteins with a more regulatory role mostly in animals . This entry includes spectrin alpha and beta subunits, alpha-actinin and dystrophin .
Wnt protein, conserved site (Wnt_CS)
Type: Conserved_site

Wnt-1 (previously known as int-1) is a proto-oncogene induced by the integration of the mouse mammary tumor virus. It is thought to play a role in intercellular communication and seems to be a signalling molecule important in the development of the central nervous system (CNS). The sequence of wnt-1 is highly conserved in mammals, fish, and amphibians.

Wnt-1 is a member of a large family of related proteins that are all thought to be developmental regulators. These proteins are known as wnt-2 (also known as irp), wnt-3 up to wnt-15. At least four members of this family are present in Drosophila; one of them, wingless (wg), is implicated in segmentation polarity.

All these proteins share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulfide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters.

Signal transduction by the Wnt family of ligands is mediated by the binding to the extracellular domain fz of Frizzled receptors. It can lead to either the activation of dishvelled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes or be coupled to the inositol signaling pathway and PKC activation, depending on the type of Frizzled receptor .

This entry represents a conserved region including three cysteines.
Alanine-tRNA ligase, class IIc, anti-codon-binding domain superfamily (Ala-tRNA-ligase_IIc_anticod-bd)
Type: Homologous_superfamily

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 .
Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily (Thr/Ala-tRNA-synth_IIc_edit)
Type: Homologous_superfamily

This superfamily represents a structural domain containing a two-layer core α/β structure: α-β(2)-α-β(2). This domain is thought to be a putative editing domain found in the N-terminal part of threonyl-tRNA synthetase (ThrRS), the C-terminal of alanyl-tRNA synthetase (AlaRS), and as the stand-alone hypothetical protein

from the archaea Pyrococcus horikoshii ; probable circular permutation of LuxS .

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 .
Alanyl-tRNA synthetase, class IIc, N-terminal (Ala-tRNA-synth_IIc_N)
Type: Domain

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 .

Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (

) is an alpha4 tetramer that belongs to class IIc.
Alanyl-tRNA synthetase, class IIc, core domain (Ala-tRNA-synth_IIc_core)
Type: Domain

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 .

Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (

) is an alpha4 tetramer that belongs to class IIc.
S-adenosylmethionine decarboxylase, conserved site (S-AdoMet_deCO2ase_CS)
Type: Conserved_site

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.
Ubiquinone biosynthesis hydroxylase, UbiH/UbiF/VisC/COQ6, conserved site (Ubi_Hdrlase_CS)
Type: Conserved_site

This entry represents FAD-dependent hydroxylases (monooxygenases) which are all believed to act in the aerobic ubiquinone biosynthesis pathway . A separate set of hydroxylases, as yet undiscovered, are believed to be active under anaerobic conditions . In Escherichia coli, three enzyme activities have been described: UbiB (which acts first at position 6, see

), UbiH (which acts at position 4, ) and UbiF (which acts at position 5, ). UbiH and UbiF are similar to one another and form the basis of this subfamily. Interestingly, E. coli contains another hydroxylase gene, called visC, that is highly similar to UbiF, adjacent to UbiH and, when mutated, results in a phenotype similar to that of UbiH (which has also been named visB) . Several other species appear to have three homologs in this family, although they assort themselves differently on phylogenetic trees (e.g. Xylella and Mesorhizobium) making it difficult to ascribe a specific activity to each one. Eukaryotes appear to have only a single homologue in this subfamily (COQ6, ) which complements UbiH, but also possess a non-orthologous gene, COQ7 which complements UbiF.

This entry represents the conserved site of the ubiquinone biosynthesis hydroxylase enzyme.
Aldo/keto reductase, conserved site (Aldo/ket_reductase_CS)
Type: Conserved_site

This entry represents three conserved sites found in members of the aldo/keto reductase family. The third site, located in the C-terminal, is centered on a lysine residue whose chemical modification, in aldose and aldehyde reductases, affect the catalytic efficiency.

The aldo-keto reductase family includes a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and many others . All possess a similar structure, with a β-α-β fold characteristic of nucleotide binding proteins . The fold comprises a parallel β8/α8 barrel, which contains a novel NADP-binding motif. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the β sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones .

Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases .

Some proteins of this entry contain a K+ ion channel beta chain regulatory domain; these are reported to have oxidoreductase activity .
Peptidyl-tRNA hydrolase, conserved site (Pept_tRNA_hydro_CS)
Type: Conserved_site

This entry represents two conserved regions that each contain an histidine. The first of these regions is located in the N-terminal part of the protein, the other in the central part.

Peptidyl-tRNA hydrolase (

) (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis . Bacterial PTH has been found to be evolutionary related to a yeast protein . This enzyme is interesting as a potential target for the discovery of new antimicrobial agents as it is critical for the viability of bacteria [

}. It folds into a single α/β globular domain with seven β-strands forming a twisted mixed central β-sheet, surrounded by a total of six helices .
Tryptophanase, conserved site (Tryptophanase_CS)
Type: Conserved_site

Tryptophanase (tryptophan indole-lyase, TNase) (

) and tyrosine phenol-lyase (TPL) (

) are related pyridoxal-phosphate dependent homotetrameric enzymes that catalyse the reversible hydrolytic cleavage of L-tryptophan or L-tyrosine to indole or phenol, respectively, and ammonium pyruvate. These two enzymes are very similar in sequence and structure, but show strict substrate specificity. Both TNase and TPL may react by a rare S(E)2-type mechanism .

This entry represents the conserved site associated to the central region of the sequence, the pyridoxal-phosphate group is attached to the lysine residue in the central section of the sequence.
L-lactate dehydrogenase, active site (L-lactate_DH_AS)
Type: Active_site

NAD-dependent L-lactate dehydrogenases from bacteria and eukaryotes functions as the final step in anaerobic glycolysis. Although lactate dehydrogenases have in some cases been mistaken for malate dehydrogenases due to the similarity of these two substrates and the apparent ease with which evolution can toggle these activities, critical residues have been identified which can discriminate between the two activities.

This entry represents the active site of L-lactate dehydrogenase, and includes a conserved histidine which is essential to the catalytic mechanism.
Heat shock protein 70, conserved site (Heat_shock_70_CS)
Type: Conserved_site

Heat shock proteins, Hsp70 chaperones help to fold many proteins. Hsp70 assisted folding involves repeated cycles of substrate binding and release. Hsp70 activity is ATP dependent. Hsp70 proteins are made up of two regions: the amino terminus is the ATPase domain and the carboxyl terminus is the substrate binding region .

Hsp70 proteins have an average molecular weight of 70kDa . In most species,there are many proteins that belong to the hsp70 family. Some of these are only expressed under stress conditions (strictly inducible), while some are present in cells under normal growth conditions and are not heat-inducible (constitutive or cognate) . Hsp70 proteins can be found in different cellular compartments(nuclear, cytosolic, mitochondrial, endoplasmic reticulum, for example).

This entry represents three conserved sites of the heat shock 70 protein family.
Gas vesicle C repeat (Gas_vesicle_C_repeat)
Type: Repeat

Gas vesicles are small, hollow, gas filled protein structures found in several cyanobacterial and archaebacterial microorganisms . They allow the positioning of the bacteria at the favorable 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. GVPc is a minor constituent of gas vesicles and seems to be located on the outer surface. Structurally, cyanobacterial GVPc consists of four or five tandem repeats of a 33 residue sequence flanked by sequences of 18 and 10 residues at the N- and C-termini, respectively.
Transcription factor, T-box, conserved site (TF_T-box_CS)
Type: Conserved_site

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, for differentiation and organogenesis and also have been associated to multiple aspects of development and in adult terminal cell-type differentiation in different animal lineages . The T-box is defined as the minimal region within the T-box protein that is both necessary and sufficient for sequence-specific DNA binding, all members of the family so far examined bind to the DNA consensus sequence TCACACCT and function as transcriptional repressors and/or activators . The T-box is a relatively large DNA-binding domain, generally comprising about a third of the entire protein (17-26kDa) .

These genes were uncovered on the basis of similarity to the DNA binding domain of Mus musculus (Mouse) Brachyury (T) gene product, which similarity is the defining feature of the family. The Brachyury gene is named for its phenotype, which was identified 70 years ago as a mutant mouse strain with a short blunted tail. The gene, and its paralogues, have become a well-studied model for the family, and hence much of what is known about the T-box family is derived from the murine Brachyury gene.

Consistent with its nuclear location, Brachyury protein has a sequence-specific DNA-binding activity and can act as a transcriptional regulator . Homozygous mutants for the gene undergo extensive developmental anomalies, thus rendering the mutation lethal . The postulated role of Brachyury is as a transcription factor, regulating the specification and differentiation of posterior mesoderm during gastrulation in a dose-dependent manner .

T-box proteins tend to be expressed in specific organs or cell types, especially during development, and they are generally required for the development of those tissues, for example, Brachyury is expressed in posterior mesoderm and in the developing notochord, and it is required for the formation of these cells in mice .
Asp/Glu racemase, active site 1 (Asp/Glu_racemase_AS_1)
Type: Active_site

Aspartate racemase (

) and glutamate racemase (

) are two evolutionary related bacterial enzymes that do not seem to require a cofactor for their activity . Glutamate racemase, which interconverts L-glutamate into D-glutamate, is required for the biosynthesis of peptidoglycan and some peptide-based antibiotics such as gramicidin S.
In addition to characterised aspartate and glutamate racemases, this family also includes a hypothetical protein from Erwinia carotovora and one from Escherichia coli (ygeA).

Two conserved cysteines are present in the sequence of these enzymes. They are expected to play a role in catalytic activity by acting as bases in proton abstraction from the substrate. This entry represents a conserved region containing the first cysteine.
Ribonuclease T2, His active site 1 (RNase_T2_His_AS_1)
Type: Active_site

The fungal ribonucleases T2 from Aspergillus oryzae, M from Aspergillus saitoi and Rh from Rhizopeus niveus are structurally and functionally related 30 Kd glycoproteins that cleave the 3'-5' internucleotide linkage of RNA via a nucleotide 2',3'-cyclic phosphate intermediates (

).

Two histidines residues have been shown to be involved in the catalytic mechanism of RNase T2 and Rh. These residues and the region around them are highly conserved.
Phosphoglucose isomerase, conserved site (Phosphoglucose_isomerase_CS)
Type: Conserved_site

Phosphoglucose isomerase (

) (PGI) is a dimeric enzyme that catalyses the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. The multifunctional protein, PGI, is also known as neuroleukin (a neurotrophic factor that mediates the differentiation of neurons), autocrine motility factor (a tumour-secreted cytokine that regulates cell motility), differentiation and maturation mediator and myofibril-bound serine proteinase inhibitor, and has different roles inside and outside the cell. In the cytoplasm, it catalyses the second step in glycolysis, while outside the cell it serves as a nerve growth factor and cytokine .