SII-SWORD/CoKE huggingface dataset:
Arginine-tRNA ligase (Arg-tRNA-ligase)
Type: Family

Arginine-tRNA ligase (

) has been crystallized and preliminary X-ray crystallographic analysis of yeast arginine-tRNA ligase-yeast tRNAArg complexes is available .

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 .
Metallo-beta-lactamase (Metallo-B-lactamas)
Type: Domain

Metallo beta lactamases exhibit low sequence identity between enzymes but they are structurally similar. They have a characteristic α-β/β-α sandwich fold in which the active site is at the interface between domains. Apart from the beta-lactamases and metallo-beta-lactamases, a number of other proteins contain this domain and share the same fold type . These proteins include thiolesterases, members of the glyoxalase II family, that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid and a competence protein that is essential for natural transformation in Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the competence protein these proteins bind two zinc ions per molecule as cofactor.
Photosystem I PsaA/PsaB (PSI_PsaA/B)
Type: Family

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. PSI is found in the chloroplast of plants and cyanobacteria. The electron transfer components of the reaction centre of PSI are a primary electron donor P-700 (chlorophyll dimer) and five electron acceptors: A0 (chlorophyll), A1 (a phylloquinone) and three 4Fe-4S iron-sulphur centres: Fx, Fa, and Fb.

PsaA and psaB, two closely related proteins, are involved in the binding of P700, A0, A1, and Fx. psaA and psaB are both integral membrane proteins of 730 to 750 amino acids that seem to contain 11 transmembrane segments. The Fx 4Fe-4S iron-sulphur centre is bound by four cysteines; two of these cysteines are provided by the psaA protein and the two others by psaB. The two cysteines in both proteins are proximal and located in a loop between the ninth and tenth transmembrane segments. A leucine zipper motif seems to be present downstream of the cysteines and could contribute to dimerisation of psaA/psaB.
Glucose-6-phosphate dehydrogenase (G6P_DH)
Type: Family

Glucose-6-phosphate dehydrogenase (

) (G6PDH) is a ubiquitous protein, present in bacteria and all eukaryotic cell types . The enzyme catalyses the the first step in the pentose pathway, i.e. the conversion of glucose-6-phosphate to gluconolactone 6-phosphate in the presence of NADP, producing NADPH. The ubiquitous expression of the enzyme gives it a major role in the production of NADPH for the many NADPH-mediated reductive processes in all cells, and is critical for NADPH homeostasis and redox regulation . Deficiency of G6PDH is a common genetic abnormality affecting millions of people worldwide. Many sequence variants, most caused by single point mutations, are known, exhibiting a wide variety of phenotypes with the distinctive one being chronic and drug- or food-induced hemolytic anemia, attributed to the inability to produce NADPH and withstand harmful oxidants in erythrocyte cells .
Cysteine-rich secretory protein-related (CRISP-related)
Type: Family

The cysteine-rich secretory proteins (Crisp) are predominantly found in the mammalian male reproductive tract as well as in the venom of reptiles. This family includes mammalian testis-specific protein (Tpx-1), also known as cysteine-rich secretory protein 2 (CRISP2) ; venom allergen 5 from vespid wasps and venom allergen 3 from fire ants, which are potent allergens that mediate allergic reactions to stings insects of the Hymenoptera family ; scoloptoxins from Scolopendra dehaani (Thai centipede) ; plant pathogenesis proteins of the PR-1 family , which are synthesised during pathogen infection or other stress-related responses; allurin, a sperm chemoattractant , serotriflin , etc.

The precise function of some of these proteins is still unclear. Tpx-1 or CRISP2 may regulate some ion channels' activity and thereby regulate calcium fluxes during sperm capacitation .

This entry also includes antigen 5 like allergen Cul n 1 from biting midge salivary glands and Protein lon-1 from Caenorhabditis elegans that regulates body size morphogenesis, but does not affect male tail development .
Synaptophysin/synaptoporin (Synaptophysin/porin)
Type: Family

Synaptophysin and synaptoporin are related glycoproteins: they are the major integral membrane proteins of a certain class of small neurosecretory vesicles, although they may also be found in vesicles of various non-endocrine cells . The polypeptide chain spans the membrane four times and possibly acts as an ion or solute channel.
Glycoside hydrolase, family 59 (Glyco_hydro_59)
Type: Family

Glycoside hydrolase family 59

comprises enzymes with only one known activity; galactocerebrosidase (

).

Globoid cell leukodystrophy (Krabbe disease) is a severe, autosomal recessive disorder that results from deficiency of galactocerebrosidase (GALC) activity . GALC is responsible for the lysosomal catabolism of certain galactolipids, including galactosylceramide and psychosine .

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.
Nitrite reductase, copper-type (NO2-reductase_Cu)
Type: Family

These enzymes are involved in nitrate assimilation in the denitrification pathway. The 3D structure of the copper-containing nitrite reductase (NIR) from Achromobacter cycloclastes has been determined to 2.3A resolution . The enzyme is a trimer, each monomer of which contains two Greek key β-barrel domains (similar to that of plastocyanin) and houses two copper sites. The two copper atoms in the monomer comprise a type I copper site (Cu-I: two His, one Cys and one Met ligand) that plays a crucial role for electron transfer from pseudoazurin to the type II copper site (Cu-II: three His and one solvent ligand), the catalytic centre of NIR for the reduction of nitrite. The Cu-II site lies at the bottom of a 12A deep solvent channel and is the site to which the substrate (NO2-) binds .
Translation initiation factor 3 (Translation_initiation_fac_3)
Type: Family

Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit . The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 .
Nuclear transcription factor Y subunit A (NFYA)
Type: Family

Diverse DNA binding proteins are known to bind the CCAAT box, a common cis- acting element found in the promoter and enhancer regions of a large number of genes in eukaryotes. Amongst these proteins is one known as the CCAAT-binding factor (CBF) or nuclear transcription factor Y (NF-Y) . CBF is a heteromeric transcription factor that consists of two different components both needed for DNA-binding.

The HAP protein complex of yeast binds to the upstream activation site of cytochrome C iso-1 gene (CYC1) as well as other genes involved in mitochondrial electron transport and activates their expression. It also recognises the sequence CCAAT and is structurally and evolutionary related to CBF.

The first subunit of CBF is known as CBF-A or NF-YB in vertebrates, and HAP3 in budding yeast. The second subunit is known as CBF-B or NF-YA in vertebrates and HAP2 in budding yeast. It is a protein of 265 to 350 amino-acid residues which contains a highly conserved region of about 60 residues. This region, called the 'essential core' , seems to consist of two subdomains: an N-terminal subunit-association domain and a C-terminal DNA recognition domain.

This entry represents the NF-YA subunit.
Estrogen receptor (Estr_rcpt)
Type: Family

Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands . The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner . In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.

NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.

The oestrogen receptors (ERs) are steroid or nuclear hormone receptors that act as transcription regulators involved in diverse physiological functions. Oestrogen receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. The ER consists of three functional and structural domains: an N-terminal modulatory domain, a highly conserved DNA-binding domain that recognises specific sequences (

), and a C-terminal ligand-binding domain (

).

The N-terminal modulatory domain spans the first 180 residues and contains the activation function 1 (AF1) region. Nuclear receptors differ considerably with respect to AF1 activity and regulation, as it is a poorly conserved region . There is another activation function region, namely AF2, which resides in the C-terminal end of the ligand-binding domain. Transcription activation is facilitated by both AF1 and AF2, which appear to act synergistically in the ER complex . For example, the ER can recruit TIF2 (transcription intermediary factor 2) via the AF1 and AF2 regions, whose synergistic action results in the activation of transcription.
Zinc finger, TRAF-type (Znf_TRAF)
Type: Domain

This entry represents TRAF-type zinc finger domains. Some of the proteins that have this domain are mammalian signal transducers associated with the cytoplasmic domain of the 75kDa tumour necrosis factor receptor . A heterocomplex, homodimer or heterodimer of TRAF1 and TRAF2, binds to the N-terminal of the inhibitor of apoptosis proteins 1 and 2 (IAPS) and recruits them to the tumour necrosis factor receptor 2. Other proteins containing this domain include F45G2.6 protein from Caenorhabditis elegans and DG17 protein from Dictyostelium discoideum (Slime mold).

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Phytochrome (Phytochrome)
Type: Family

Phytochromes are a class of photoreceptor found in plants, bacteria and fungi, which are used to detect light. In plants, phytochromes mediate physiological and developmental responses to changes in red and far-red light conditions . The protein undergoes reversible photochemical conversion between a biologically-inactive red light-absorbing form and the active far-red light-absorbing form. Phytochrome is a dimer of identical 124kDa subunits, each of which contains a linear tetrapyrrole chromophore, covalently-attached via a Cys residue.

In Arabidopsis thaliana, there are genes for at least five phytochrome proteins . These photoreceptors control such responses as germination, stem elongation, flowering, gene expression, and chloroplast and leaf development. It is not yet known which red light responses are controlled by which phytochrome species, or whether the different phytochromes have overlapping functions . Synechocystis sp. (strain PCC 6803) hypothetical protein slr0473 contains a domain similar to that of plants phytochrome and seems also to bind a chromophore.
Dihydroorotate dehydrogenase, conserved site (Dihydroorotate_DH_CS)
Type: Conserved_site

Dihydroorotate dehydrogenase (

) (DHOdehase) catalyses the fourth step in the
de novo
biosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein while in other eukaryotes it is found in the mitochondria .
Glycosyl transferase, family 1 (Glyco_trans_1)
Type: Domain

Proteins containing this domain transfer UDP, ADP, GDP or CMP linked sugars to a variety of substrates, including glycogen, fructose-6-phosphate and lipopolysaccharides. The bacterial enzymes are involved in various biosynthetic processes that include exopolysaccharide biosynthesis, lipopolysaccharide core biosynthesis and the biosynthesis of the slime polysaccaride colanic acid. Mutations in this domain of the human N-acetylglucosaminyl-phosphatidylinositol biosynthetic protein are the cause of paroxysmal nocturnal hemoglobinuria (PNH) , an acquired hemolytic blood disorder characterised by venous thrombosis, erythrocyte hemolysis, infections and defective hematopoiesis.

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'.
Phycobilisome linker domain (PBS_linker_dom)
Type: Domain

Phycobilisomes (PBSs) are the major light-harvesting systems in cyanobacteria and red algae. PBS is a supercomplex that is composed of a core complex and multiple peripheral rod complexes. Typically, the core consists of two or five cylinders lying on the membrane with, in most cases, multiple rods radiating from the core to form a hemidiscoidal structure. The building units of the core cylinders and the peripheral rods are trimeric and hexameric discs, in which a monomer consists of a pair of related phycobiliproteins (PBPs), such as phycorerythrins, phycoerythrocyanins, phycocyanins, and allophycocyanins. The discs are connected to each other via specific linker polypeptides to form peripheral rods or core cylinders. Linker polypeptides share a conserved domain of ~180 residues, which can be present in one or multiple copies .
Filamin/ABP280 repeat (Filamin/ABP280_rpt)
Type: Repeat

The many different actin cross-linking proteins share a common architecture, consisting of a globular actin-binding domain and an extended rod. Whereas their actin-binding domains consist of two calponin homology domains (see

), their rods fall into three families.

The rod domain of the family including the Dictyostelium discoideum (Slime mould) gelation factor (ABP120) and human filamin (ABP280) is constructed from tandem repeats of a 100-residue motif that is glycine and proline rich . The gelation factor's rod contains 6 copies of the repeat, whereas filamin has a rod constructed from 24 repeats. The resolution of the 3D structure of rod repeats from the gelation factor has shown that they consist of a β-sandwich, formed by two β-sheets arranged in an immunoglobulin-like fold . Because conserved residues that form the core of the repeats are preserved in filamin, the repeat structure should be common to the members of the gelation factor/filamin family.

The head to tail homodimerisation is crucial to the function of the ABP120 and ABP280 proteins. This interaction involves a small portion at the distal end of the rod domains. For the gelation factor it has been shown that the carboxy-terminal repeat 6 dimerises through a double edge-to-edge extension of the β-sheet and that repeat 5 contributes to dimerisation to some extent .
Ependymin (Ependymin)
Type: Family

Ependymins are secretory proteins found predominantly in the cerebrospinal fluid of teleost fish . A bound form of the glycoproteins is associated with the extracellular matrix, probably with collagen fibrils, that may be the functional form of ependymins . The proteins bind calcium via N-linked sialic acid residues. The molecular function of ependymins appear to be related to cell contact phenomena involving the extracellular matrix .
Geminivirus AL1 replication-associated protein, CLV type (Gemini_AL1_CLV)
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.
Photosystem I reaction centre subunit VIII (PSI_PsaI)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

This entry represents subunit VIII (PsaI) of the photosystem I (PSI) reaction centre. PSI is located, along with photosystem II (PSII), in the thylakoid photosynthetic membranes of plants, green algae and cyanobacteria. The crystal structure of PSI from the thermophilic cyanobacterium Synechococcus elongatus (Thermosynechococcus elongatus) has 12 protein subunits and 127 cofactors comprising 96 chlorophylls, 2 phylloquinones, 3 4Fe4S clusters, 22 carotenoids, 4 lipids, and a putative calcium ion . PsaI consists of a single transmembrane helix, and has a crucial role in aiding normal structural organisation of PsaL within the PSI complex and the absence of PsaI alters PsaL organisation, leading to a small, but physiologically significant, defect in PSI function . PsaL encodes a subunit of PSI and is necessary for trimerisation of PSI. PsaL may constitute the trimer-forming domain in the structure of PSI .