SII-SWORD/CoKE huggingface dataset:
Bindin (Bindin)
Type: Family

Bindin, the major protein component of the acrosome granule of sea urchin sperm, mediates species-specific adhesion of sperm to the egg surface during fertilisation . The protein coats the acrosomal process after externalisation by the acrosome reaction; it binds to sulphated, fucose-containing polysaccharides on the vitelline-layer receptor proteoglycans that cover the egg plasma membrane. Bindins from different genera show high levels of sequence similarity in both the mature bindin domain and in the probindin precursor region. The most highly conserved region is a 42-residue segment in the central portion of the mature bindin protein. This domain may be responsible for conserved functions of bindin, while the more highly divergent flanking regions may be responsible for its species-specific properties .
Precursor fusion glycoprotein F0, Paramyxoviridae (Fusion_F0_Paramyxovir)
Type: Family

The fusion glycoproteins from this family are found in ssRNA negative-strand viruses. This protein directs fusion of viral and cellular membranes, resulting in viral penetration, and can direct fusion of infected cells with adjoining cells, resulting in the formation of syncytia. The mature form is a dimer of polypeptides F1 and F2 linked by a disulphide bond .
Human immunodeficiency virus 1, envelope glycoprotein Gp120 (HIV1_Gp120)
Type: Domain

The envelope glycoprotein Gp160 of HIV1 is cleaved into the surface protein Gp120 and the transmembrane protein Gp41. The entry of HIV requires interaction of viral Gp120 with the CD4 glycoprotein and a chemokine receptor on the cell surface . This entry represents the GP120 core protein, which is released after Gp160 is proteolytically cleaved in the trans-Golgi and activated by cellular furin or furin-like proteases to produce gp120 and gp41 .
Cytochrome b245, heavy chain (Cyt_b245_heavy_chain)
Type: Family

Phagocytes form the first line of defence against invasion by micro-organisms. Engulfing of bacteria by neutrophils during phagocytosis is accompanied by a respiratory burst. Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous disease (CGD) . Proteins in this entry are calcium-dependent NADPH oxidases that generates superoxide, including NADPH oxidase 1-4 from animals (also known as Cytochrome b-245 heavy chain) and Respiratory burst oxidase homologue proteins from plants. NADPH oxidase 2 is the catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion .
Interleukin-2 (IL-2)
Type: Family

T-Lymphocytes regulate the growth and differentiation of certain lymphopoietic and haemopoietic cells through the release of various secreted protein factors . These factors, which include interleukin-2 (IL2), are secreted by lectin- or antigen-stimulated T-cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T-cells. In addition, it acts on some B-cells, via receptor-specific binding , as a growth factor and antibody production stimulant . The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity . Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly-defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF) .
MCP methyltransferase, CheR-type (CheR_MeTrfase)
Type: Domain

CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains . Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase , which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues .

The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A . The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal α/β domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region .
Enhancer of rudimentary (ERH)
Type: Family

The Drosophila protein 'enhancer of rudimentary' (gene (e(r)) is a small protein of 104 residues whose function is not yet clear. From an evolutionary point of view, it is highly conserved and has been found to exist in probably all multicellular eukaryotic organisms. ERH has been implicated in the regulation of pyrimidine biosynthesis, DNA replication, transcription, mRNA splicing, cellular proliferation, tumorigenesis, and the Notch signaling pathway . Fission yeast homologue of ERH is implicated in meiotic mRNA elimination during vegetative growth. It forms a stoichiometric complex with Mmi1 to promote meiotic mRNA decay and facultative heterochromatin assembly in which the formation of ERH dimer is essential for the complex function.

ERH has been shown to interact with SAFB1/SAFB2 (scaffold attachment factor-B 1/2) at the nuclear matrix to regulate SR protein phosphorylation .
FAS1 domain (FAS1_domain)
Type: Domain

The FAS1 (fasciclin-like) domain is an extracellular module of about 140 amino acid residues. It has been suggested that the FAS1 domain represents an ancient cell adhesion domain common to plants and animals ; related FAS1 domains are also found in bacteria .

The crystal structure of FAS1 domains 3 and 4 of fasciclin I from Drosophila melanogaster (Fruit fly) has been determined, revealing a novel domain fold consisting of a seven-stranded β wedge and at least five α helices; two well-ordered N-acetylglucosamine groups attached to a conserved asparagine are located in the interface region between the two FAS1 domains . Fasciclin I is an insect neural cell adhesion molecule involved in axonal guidance that is attached to the membrane by a GPI-anchored protein.

FAS1 domains are present in many secreted and membrane-anchored proteins. These proteins are usually GPI anchored and consist of: (i) a single FAS1 domain, (ii) a tandem array of FAS1 domains, or (iii) FAS1 domain(s) interspersed with other domains.

Proteins known to contain a FAS1 domain include:

Fasciclin I (4 FAS1 domains).

Human TGF-beta induced Ig-H3 (BIgH3) protein (4 FAS1 domains), where the FAS1 domains mediate cell adhesion through an interaction with alpha3/beta1 integrin; mutation in the FAS1 domains result in corneal dystrophy .

Volvox major cell adhesion protein (2 FAS1 domains) .

Arabidopsis fasciclin-like arabinogalactan proteins (2 FAS1 domains) .

Mammalian stabilin protein, a family of fasciclin-like hyaluronan receptor homologues (7 FAS1 domains).

Human extracellular matrix protein periostin (4 FAS1 domains).

Bacterial immunogenic protein MPT70 (1 FAS1 domain) .

The FAS1 domains of both human periostin (

) and BIgH3 (

) proteins were found to contain vitamin K-dependent gamma-carboxyglutamate residues . Gamma-carboxyglutamate residues are more commonly associated with GLA domains (

), where they occur through post-translational modification catalysed by the vitamin K-dependent enzyme gamma-glutamylcarboxylase.
RNA polymerase, subunit H/Rpb5 C-terminal (RNA_pol_subH/Rpb5_C)
Type: Domain

Prokaryotes contain a single DNA-dependent RNA polymerase (RNAP;

) that is responsible for the transcription of all genes, while eukaryotes have three classes of RNAPs (I-III) that transcribe different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. Certain subunits of RNAPs, including RPB5 (POLR2E in mammals), are common to all three eukaryotic polymerases. RPB5 plays a role in the transcription activation process. Eukaryotic RPB5 has a bipartite structure consisting of a unique N-terminal region (

), plus a C-terminal region that is structurally homologous to the prokaryotic RPB5 homologue, subunit H (gene rpoH) .

This entry represents prokaryotic subunit H and the C-terminal domain of eukaryotic RPB5, which share a two-layer α/β fold, with a core structure of β/α/β/α/β(2).
Late protein L2 (Late_L2)
Type: Family

This family includes the L2 minor capsid protein, a late protein from Human papillomavirus (HPV). HPV are dsDNA viruses with no RNA stage in their replication cycle. Their dsDNA is contained within a capsid composed of 72 L1 capsomers and about 36 L2 minor capsid proteins. L2 minor capsid proteins enter the nucleus twice during infection: in the initial phase after virion disassembly, and in the productive phase when it assembles into replicated virions along with L1 major capsid proteins. L2 proteins contain two nuclear localisation signals (NLSs), one at the N-terminal (nNLS) and the other at the C-terminal (cNLS). L2 uses its NLSs to interact with a network of karyopherins in order to enter the nucleus via several import pathways. L2 from HPV types 11 and 16 was shown to interact with karyopherins Kapbeta(2) and Kapbeta(3) . L2 capsid proteins can also interact with viral dsDNA, facilitating its release from the endocytic compartment after viral uncoating.
Herpsevirus envelope glycoprotein M (Herpes_glycop_M)
Type: Family

Envelope glycoprotein M (gM) is well conserved across the herpesvirus family. It is important for virion assembly and egress .
Green fluorescent protein, GFP (Green_fluorescent_prot)
Type: Family

The green fluorescent protein (GFP) is found in the jellyfish (Aequorea victoria), and functions as an energy-transfer acceptor. It fluoresces
in vivo
upon receiving energy from the
Ca
2+
-activated photoprotein aequorin. The protein absorbs light maximally at 395 nm and exhibits a smaller absorbance peak at 470 nm. The fluorescence emission spectrum peaks at 509 nm with a shoulder at 540 nm. The protein is produced in the photocytes and contains a chromophore, which is composed of modified amino acid residues. The chromophore is formed upon cyclisation of the residues ser-dehydrotyr-gly. There are several other members of the GFP family, which are able to fluoresce different colours, sveral of which are non-fluorescent . These proteins are all essentailly encoded by single genes, since both the substrate and the catalytic enzyme for pigment biosynthesis are provided within a single polypeptide chain .
Peptidase M29 (Peptidase_M29)
Type: Family

This group of metallopeptidases belong to MEROPS peptidase family M29 (aminopeptidase T family, clan M-). The protein fold of the peptidase domain and the active site residues are not known for any members of the thermophilic metallo-aminopeptidases family .
Ribonucleotide reductase large subunit, C-terminal (RNR_lg_C)
Type: Domain

Ribonucleotide reductase (RNR,

) catalyses the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in their genomes.

Ribonucleotide reductase is an oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain .

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals, the function of each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction process by hydrogen atom abstraction from the ribonucleotide . The radical-based reaction involves five cysteines: two of these are located at adjacent anti-parallel strands in a new type of ten-stranded α/β-barrel; two others reside at the carboxyl end in a flexible arm; and the fifth, in a loop in the centre of the barrel, is positioned to initiate the radical reaction . There are several regions of similarity in the sequence of the large chain of prokaryotes, eukaryotes and viruses spread across 3 domains: an N-terminal domain common to the mammalian and bacterial enzymes; a C-terminal domain common to the mammalian and viral ribonucleotide reductases; and a central domain common to all three .

This entry represents the C-terminal region of the large (alpha) subunit of RNRs from all domains in life.
Cyclin-dependent kinase, regulatory subunit (Cyclin-dep_kinase_reg-sub)
Type: Family

In eukaryotes, cyclin-dependent protein kinases interact with cyclins to regulate cell cycle progression, and are required for the G1 and G2 stages of cell division . The proteins bind to a regulatory subunit, cyclin-dependent kinase regulatory subunit (CKS), which is essential for their function. This regulatory subunit is a small protein of 79 to 150 residues. In yeast (gene CKS1) and in fission yeast (gene suc1) a single isoform is known, while mammals have two highly related isoforms. The regulatory subunits exist as hexamers, formed by the symmetrical assembly of 3 interlocked homodimers, creating an unusual 12-stranded β-barrel structure . Through the barrel centre runs a 12A diameter tunnel, lined by 6 exposed helix pairs . Six kinase units can be modelled to bind the hexameric structure, which may thus act as a hub for cyclin-dependent protein kinase multimerisation .
Acetate transporter GPR1/Ato2/SatP-like (Gpr1/Fun34/SatP-like)
Type: Family

This family of evolutionary related proteins includes Yarrowia lipolytica (Candida lipolytica) glyxoxylate pathway regulator GPR1 , Saccharomyces cerevisiae Ady2, Fun34/Ato2 and Ato3 ; fission yeast Mug86 (also known as SpAC5D6.09c); Escherichia coli SatP (YaaH) ; and the Acetate transporter protein patA from Penicillium expansum. The uncharacterised protein AlcS from Aspergillus fumigatus and Emericella nidulans is also included in this entry. They contain six transmembrane helices that surrounds the central channel pore, involved in transport .

Saccharomyces cerevisiae Ady2, also known as ATO1, is a transporter protein required for ammonia export and acetate uptake and resistance and is necessary for up-regulation and down-regulation of meiotic plaque (MP) component levels in a dependency on external acetate . Gpr1p affects sensitivity to acetic acid in the yeast Yarrowia lipolytica . Ato2 and Ato3 are required for ammonia export . AcpA may be an acetate transporter that is essential for acetate permease activity in the hyphal fungus Aspergillus nidulans . SatP is involved in the uptake of acetate and succinate . PatA is part of the gene cluster that mediates the biosynthesis of patulin, an acetate-derived tetraketide mycotoxin produced by several fungal species that shows antimicrobial properties against several bacteria .
Transcription regulator LuxR, C-terminal (Tscrpt_reg_LuxR_C)
Type: Domain

This domain is a DNA-binding, helix-turn-helix (HTH) domain of about 65 amino acids, present in transcription regulators of the LuxR/FixJ family of response regulators. The domain is named after Vibrio fischeri luxR, a transcriptional activator for quorum-sensing control of luminescence. LuxR-type HTH domain proteins occur in a variety of organisms. The DNA-binding HTH domain is usually located in the C-terminal region; the N-terminal region often containing an autoinducer-binding domain or a response regulatory domain. Most luxR-type regulators act as transcription activators, but some can be repressors or have a dual role for different sites. LuxR-type HTH regulators control a wide variety of activities in various biological processes.

The luxR-type, DNA-binding HTH domain forms a four-helical bundle structure. The HTH motif comprises the second and third helices, known as the scaffold and recognition helix, respectively. The HTH binds DNA in the major groove, where the N-terminal part of the recognition helix makes most of the DNA contacts. The fourth helix is involved in dimerisation of gerE and traR. Signalling events by one of the four activation mechanisms described below lead to multimerisation of the regulator. The regulators bind DNA as multimers .

LuxR-type HTH proteins can be activated by one of four different mechanisms:

1) Regulators which belong to a two-component sensory transduction system where the protein is activated by its phosphorylation, generally on an aspartate residue, by a transmembrane kinase . Some proteins that belong to this category are:

Rhizobiaceae fixJ (global regulator inducing expression of nitrogen-fixation genes in microaerobiosis)

Escherichia coli and Salmonella typhimurium uhpA (activates hexose phosphate transport gene uhpT)

E. coli narL and narP (activate nitrate reductase operon)

Enterobacteria rcsB (regulation of exopolysaccharide biosynthesis in enteric and plant pathogenesis)

Bordetella pertussis bvgA (virulence factor)

Bacillus subtilis coma (involved in expression of late-expressing competence genes)

2) Regulators which are activated, or in very rare cases repressed, when bound to N-acyl homoserine lactones, which are used as quorum sensing molecules in a variety of Gram-negative bacteria :

V. fischeri luxR (activates bioluminescence operon)

Agrobacterium tumefaciens traR (regulation of Ti plasmid transfer)

Erwinia carotovora carR (control of carbapenem antibiotics biosynthesis)

E. carotovora expR (virulence factor for soft rot disease; activates plant tissue macerating enzyme genes)

Pseudomonas aeruginosa lasR (activates elastase gene lasB)

Erwinia chrysanthemi echR and Erwinia stewartii esaR

Pseudomonas chlororaphis phzR (positive regulator of phenazine antibiotic production)

Pseudomonas aeruginosa rhlR (activates rhlAB operon and lasB gene)

3) Autonomous effector domain regulators, without a regulatory domain, represented by gerE .

4) Multiple ligand-binding regulators, exemplified by malT .
ATP synthase, alpha subunit, C-terminal (ATP_synth_asu_C)
Type: Domain

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.

The F-ATPases (or F1F0-ATPases), V-ATPases (or V1V0-ATPases) and A-ATPases (or A1A0-ATPases) are composed of two linked complexes: the F1, V1 or A1 complex contains the catalytic core that synthesizes/hydrolyses ATP, and the F0, V0 or A0 complex that forms the membrane-spanning pore. The F-, V- and A-ATPases all contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis .

In F-ATPases, there are three copies each of the alpha and beta subunits that form the catalytic core of the F1 complex, while the remaining F1 subunits (gamma, delta, epsilon) form part of the stalks. There is a substrate-binding site on each of the alpha and beta subunits, those on the beta subunits being catalytic, while those on the alpha subunits are regulatory. The alpha and beta subunits form a cylinder that is attached to the central stalk. The alpha/beta subunits undergo a sequence of conformational changes leading to the formation of ATP from ADP, which are induced by the rotation of the gamma subunit, itself driven by the movement of protons through the F0 complex C subunit .

In V- and A-ATPases, the alpha/A and beta/B subunits of the V1 or A1 complex are homologous to the alpha and beta subunits in the F1 complex of F-ATPases, except that the alpha subunit is catalytic and the beta subunit is regulatory.

The structure of the alpha and beta subunits is almost identical. Each subunit consists of a N-terminal β-barrel, a central domain containing the nucleotide-binding site and a C-terminal α bundle domain of 7 and 6 helices, respectively, in the alpha and beta subunits . This entry represents the C-terminal domain of the alpha subunit.
Beta-ketoacyl synthase (Beta-ketoacyl_synthase)
Type: Family

Beta-ketoacyl-ACP synthase

(KAS) is the enzyme that catalyses the condensation of malonyl-ACP with the growing fatty acid chain. It is found as a component of a number of enzymatic systems, including fatty acid synthetase (FAS), which catalyses the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH; the multi-functional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum , which is involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme systems; Emericella nidulans multifunctional protein Wa, which is involved in the biosynthesis of conidial green pigment; Rhizobium nodulation protein nodE, which probably acts as a beta-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; narbonolide/10-deoxymethynolide synthase, which is involved in the biosynthesis of narbomycin and pikromycin in Streptomyces venezuelae ; and yeast mitochondrial protein CEM1. The condensation reaction is a two step process, first the acyl component of an activated acyl primer is transferred to a cysteine residue of the enzyme and is then condensed with an activated malonyl donor with the concomitant release of carbon dioxide.
Translational (tr)-type GTP-binding domain (T_Tr_GTP-bd_dom)
Type: Domain

Translational GTPases (trGTPases) are a family of proteins in which GTPase activity is stimulated by the large ribosomal subunit. This family includes translation initiation, elongation, and release factors and contains four subfamilies that are widespread, if not ubiquitous, in all three superkingdoms . The trGTPase family members include bacteria elongation factors, EFTu, EFG, and the initiation factor, IF2, and their archaeal homologues, the EF1, EF2, aeIF5b and aeIF2. They all contain two homologous N-terminal domains: a GTPase or G-domain, followed by an OB-domain. These translational proteins' G-domains are both structurally and functionally related to a larger family of GTPase G proteins . This entry represents the G-domain of the trGTPases.

The basic topology of the tr-type G domain consists of a six-stranded central β-sheet surrounded by five α-helices. Helices α2, α3 and α4 are on one side of the sheet, whereas α1 and α5 are on the other . GTP is bound by the CTF-type G domain in a way common for G domains involving five conserved sequence motifs termed G1-G5. The base is in contact with the NKxD (G4) and SAx (G5) motifs, and the phosphates of the nucleotide are stabilised by main- and side-chain interactions with the P loop GxxxxGKT (G1). The most severe conformational changes are observed for the two switch regions which contain the xT/Sx (G2) and DxxG (G3) motifs that function as sensors for the presence of the gamma-phosphate. A Mg(2+) ion is coordinated by six oxygen ligands with octahedral coordination geometry; two of the ligands are water molecules, two come from the beta- and gamma-phosphates, and two are provided by the side chains of G1 and G2 threonines .