SII-SWORD/CoKE huggingface dataset:
Herpesvirus UL87, C-terminal (Herpes_UL87_C)
Type: Domain

This entry represents the C-terminal domain found in protein UL87 from human cytomegalovirus and related proteins members of herpesviridae UL87 family. The function of this domain is unknown. It is also found in Epstein-Barr virus (EBV) early protein BcRF1 that is a viral factor crucial for the activation of late gene transcription following viral DNA replication during the productive cycle. BcRF1 forms a complex with the TATT motif, present in the promoter of most EBV late genes, and that this interaction is required for activation of late viral gene expression .
Herpesvirus UL16/UL94 (Herpes_UL16/UL94)
Type: Family

UL16 protein (also known as cytoplasmic envelopment protein 2) plays a role in capsid maturation including DNA packaging/cleavage . In immunofluorescence studies , UL16 was localised to the nucleus of infected cells in areas containing high concentrations of Human herpesvirus 2 (Herpes simplex virus 2) capsid proteins. These nuclear compartments have been described previously as viral assemblons and are distinct from compartments containing replicating DNA. Localization within assemblons argues for a role of UL16 encoded protein in capsid assembly or maturation .

UL94 is a human cytomegalovirus (HCMV) homologue that has been shown to be involved in facilitating secondary envelopment of virions .
Competence protein, ComC (Competence_ComC)
Type: Family

Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions .

This family consists of streptococcal competence stimulating peptide precursors, which are generally up to 50 amino acid residues long. In all the members of this family, the leader sequence is cleaved after two conserved glycine residues; thus the leader sequence is of the double- glycine type . Competence stimulating peptides (CSP) are small (less than 25 amino acid residues) cationic peptides. The N-terminal amino acid residue is negatively charged, either glutamate or aspartate. The C-terminal end is positively charged. The third residue is also positively charged: a highly conserved arginine . Some COMC proteins and their precursors (not included in this family) do not fully follow the above description.

Functionally, CSP act as pheromones, stimulating competence for genetic transformation in streptococci. In streptococci, the (CSP mediated) competence response requires exponential cell growth at a critical density, a relatively simple requirement when compared to the stationary-phase requirement of Haemophilus, or the late-logarithmic- phase of Bacillus . All bacteria induced to competence by a particular CSP are said to belong to the same pherotype, because each CSP is recognised by a specific receptor (the signalling domain of a histidine kinase ComD). Pherotypes are not necessarily species-specific. In addition, an organism may change pherotype. There are two possible mechanisms for pherotype switching: horizontal gene transfer, and accumulation of point mutations. The biological significance of pherotypes and pherotype switching is not definitively determined. Pherotype switching occurs frequently enough in naturally competent streptococci to suggest that it may be an important contributor to genetic exchange between different bacterial species .

This entry also includes proteins that form bacteriocin-like propetides with a glycine-glycine cleavage site. The bacteriocin is initially formed as a pre-propeptide and upon cleavage at the glycine-glycine cleavage site, a leader peptide and the propeptide would be formed. The propeptide then undergoes posttranslational modification before becoming functional .
Herpesvirus UL92 (Herpes_UL92)
Type: Family

Members of this family are functionally uncharacterised proteins from herpesviruses. The N terminus of these proteins contain 6 conserved cysteines and histidines that might form a zinc binding domain.
Herpesvirus UL79 (Herpes_UL79)
Type: Family

Members of the herpesvirus UL79 family also contain proteins such as U52 and gene 18 protein. UL79 plays a role in the expression of late transcripts bridging viral DNA replication and late gene expression during infection .
Transposase IS66, central domain (Transposase_IS66_central)
Type: Domain

This domain can be found in transposase IS66 from Agrobacterium tumefaciens . Transposases are necessary for efficient DNA transposition. IS66 may cause genetic and structural variations of the T region and the vir region of the octopine Ti plasmids .
Adenoviral packaging protein 3-like (L1-like)
Type: Family

This entry includes packaging protein 3 (also known as L1) I-leader protein from adenovirus. L1 is involved in viral genome packaging through its interaction with packaging protein 1 and 2 . The function of I-leader protein is not clear .
Coronavirus Orf3a/b (Coronavirus_Orf3a/b)
Type: Family

Members of this family are non-structural proteins that are found in alphacoronavirus, including Transmissible gastroenteritis virus (TGEV) and Porcine respiratory coronavirus (PRCV). These proteins are found on the same mRNA as another product, designated ORF3a and they are referred to as 3a-like accessory proteins found in multiple alpha and betacoronavirus lineages that infect bats and humans. They are transmembrane proteins of the viroporin family that form ion channels in the host membrane and have been implicated in inducing apoptosis, pathogenicity, and virus release .
Carotenoid oxygenase (Carotenoid_Oase)
Type: Family

This entry represents a number of enzymes with oxidoreductase activity, many of which acting on carotenoids. They fold into a seven-bladed β-propeller and require Fe2+ for activity.

Carotenoids such as β-carotene, lycopene, lutein and beta-cryptoxanthine are produced in plants and certain bacteria, algae and fungi, where they function as accessory photosynthetic pigments and as scavengers of oxygen radicals for photoprotection. They are also essential dietary nutrients in animals. Carotenoid oxygenases cleave a variety of carotenoids into a range of biologically important products, including apocarotenoids in plants that function as hormones, pigments, flavours, floral scents and defence compounds, and retinoids in animals that function as vitamins, visual pigments and signalling molecules . Examples of carotenoid oxygenases include:

Beta,beta-carotene 15,15'-dioxygenase (BCDO1) from animals, which cleaves β-carotene symmetrically at the central double bond to yield two molecules of retinal .

Carotenoid-cleaving dioxygenase, mitochondrial (BCDO2) from animals, which cleaves β-carotene asymmetrically to apo-10'-beta-carotenal and beta-ionone, the latter being converted to retinoic acid. Lycopene is also oxidatively cleaved .

Carotenoid 9,10(9',10')-cleavage dioxygenase (CCD) from plants, which cleaves a variety of carotenoids symmetrically at both the 9-10 and 9'-10' double bonds and catalyzes the formation of 4,9-dimethyldodeca-2,4,6,8,10-pentaene-1,12-dialdehyde from zeaxanthin .

9-cis-epoxycarotenoid dioxygenase (NCED1/2) from plants, which cleaves 9-cis xanthophylls to xanthoxin, a precursor of the hormone abscisic acid .

Apocarotenoid-15,15'-oxygenase (ACOX) from bacteria and cyanobacteria, which converts beta-apocarotenals rather than β-carotene into retinal. This protein has a seven-bladed β-propeller structure with four histidines that hold the iron active centre .

Retinoid isomerohydrolase (RPE65) from animals, which in its soluble form binds all-trans retinol, and in its membrane-bound form binds all-trans retinyl esters. RPE65 is important for the production of 11-cis retinal during visual pigment regeneration .
DUF236 repeat (DUF236)
Type: Repeat

This family represents a short repeat region found a number of C. elegans proteins of unknown function.
Systemic acquired resistance protein SAR (Sar8_2)
Type: Family

Members of this family are found in Solanaceae spp. plants, a taxonomic group (family) that includes pepper and tobacco plant species. Synthesis of these proteins is induced by Tobacco mosaic virus and salicylic acid ; indeed they are thought to be involved in the development of systemic acquired resistance (SAR) after an initial hypersensitive response to microbial infection . SAR is characterised by long-lasting resistance to infection by a wide range of pathogens, extending to plant tissues distant from the initial infection site .
Nicotianamine synthase (Nicotian_synth)
Type: Family

Nicotianamine synthase

catalyzes the trimerization of S-adenosylmethionine to yield one molecule of nicotianamine. Nicotianamine has an important role in plant iron uptake mechanisms. Plants adopt two strategies (termed I and II) of iron acquisition. Strategy I is adopted by all higher plants except graminaceous plants, which adopt strategy II . In strategy I plants, the role of nicotianamine is not fully determined: possible roles include the formation of more stable complexes with ferrous than with ferric ion, which might serve as a sensor of the physiological status of iron within a plant, or which might be involved in the transport of iron . In strategy II (graminaceous) plants, nicotianamine is the key intermediate (and nicotianamine synthase the key enzyme) in the synthesis of the mugineic family (the only known family in plants) of phytosiderophores. Phytosiderophores are iron chelators whose secretion by the roots is greatly increased in instances of iron deficiency .

The 3D structures of five example NAS from Methanothermobacter thermautotrophicus reveal the monomer to consist of a five-helical bundle N-terminal domain on top of a classic Rossmann fold C-terminal domain. The N-terminal domain is unique to the NAS family, whereas the C-terminal domain is homologous to the class I family of SAM-dependent methyltransferases. An active site is created at the interface of the two domains, at the rim of a large cavity that corresponds to the nucleotide binding site such as is found in other proteins adopting a Rossmann fold .
Membrane bound O-acyl transferase, MBOAT (MBOAT_fam)
Type: Family

The MBOAT (membrane bound O-acyl transferase) family of membrane proteins contains a variety of acyltransferase enzymes. A conserved histidine has been suggested to be the active site residue . The structure of MBOAT has been revealed .

This family includes Diacylglycerol O-acyltransferase 1 (DGAT1) and Lysophospholipid acyltransferase 7 (MBOAT7) from humans. DGAT1 catalyses the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates . It also functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders . MBOAT7 participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation .
Glycoside hydrolase family 57, N-terminal domain (Glyco_hydro_57_N)
Type: Domain

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.

Glycoside hydrolase family 57

comprises enzymes with two known activities; alpha-amylase (

) and 4-alpha-glucanotransferase (

).
Nucleoplasmin family (Nucleoplasmin)
Type: Family

The nucleoplasmin family includes nucleophosmin, nucleoplasmin and nucleoplasmin-like proteins. Nucleophosmin (also known as NPM1/B23) is a multifunctional protein that is involved in a number of cellular activities, such as ribosome maturatation and export, centrosome duplication, and response to stress stimuli . Nucleoplasmin (NPM2) is a histone chaperone for histones H2A-H2B and is highly expressed in the oocyte and through the early stages of embryogenesis .

Mutations of the NPM1 gene has been linked to acute myeloid leukemia .
Cellulose/chitin-binding protein, N-terminal (Cellulose/chitin-bd_N)
Type: Domain

This domain is found in a variety of cellulose- and chitin-binding proteins . This domain is also found in baculoviral spheroidins and spindolins , and in bacterial GlcNAc-binding protein A (gbpA) .
Protein-arginine deiminase (PAD)
Type: Family

In the presence of calcium ions, Protein-arginine deiminase (PAD) enzymes

catalyse the post-translational modification reaction responsible for the formation of citrulline residues from protein-bound arginine residues . Four PAD isotypes of PAD have been identified in mammals, a fifth may also exist. Non-mammalian vertebrates appear to have only a single PAD enzyme. All known natural substrates of PAD are proteins known to have an important structural function, such as keratin (PAD1), intermediate filaments or proteins associated with intermediate filaments. Citrulination may have consequences for the structural integrity and interactions of these proteins. Physiological levels of calcium appear to be too low to activate these enzymes suggesting a role between PAD activation and loss of calcium homeostasis during terminal differentiation and cell death (apoptosis).

In humans, PAD enzymes may be involved in cytoskeletal reorganization in the egg and early embryo . These enzymes abolish the methyltransferase activity of Nicotinamide- N-methyltransferase (NNMT) through its citrullination, which may play a role in a subset of breast cancers and several chronic disease conditions .
Acetamidase/Formamidase (FmdA_AmdA)
Type: Family

This family includes amidohydrolases of formamide

and acetamide

. The formamidase from Methylophilus methylotrophus (Bacterium W3A1) forms a homotrimer suggesting that this may be a common property of other members of this family.
Thiaminase-2/PQQC (Thiaminase-2/PQQC)
Type: Domain

Proteins containing this domain are found in all the three major phyla of life: archaebacteria, eubacteria, and eukaryotes. In Bacillus subtilis, TenA is one of a number of proteins that enhance the expression of extracellular enzymes, such as alkaline protease, neutral protease and levansucrase and has been identified as a Thiaminase 2 . The THI-4 protein, which is involved in thiamine biosynthesis, also contains this domain. The C-terminal part of these proteins consistently show significant sequence similarity to TenA proteins. This similarity was first noted with the Neurospora crassa THI-4 .
Domain of unknown function DUF237 (DUF237)
Type: Domain

This is a domain of unknown function found in mycoplasma. It is found at the C-terminal region.
TspO/MBR-related protein (TspO_MBR)
Type: Family

Members of this group are involved in transmembrane signalling. In both prokaryotes and mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway . They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria) .

Rhodobacter sphaeroides TspO (previously CrtK) is involved in signal transduction, functioning as a negative regulator of the expression of some photosynthesis genes (PpsR/AppA repressor/antirepressor regulon). This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins . It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes . A homologue of the TspO protein in Rhizobium meliloti (Sinorhizobium meliloti) is involved in regulating expression of the ndi locus in response to stress conditions . There is evidence that the S. meliloti TspO acts through, or in addition to, the FixL regulatory system.

In animals, translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor (PBR, MBR) is a mitochondrial protein (located in the outer mitochondrial membrane) where it forms a complex with several proteins of the mitochondrial permeability transition pore (MPTP). TSPO is involved in multiple processes, including regulation of cell death, cholesterol transport and steroid biosynthesis, mitochondrial respiration and oxidation and mitochondrial protein import .

These observations suggest that fundamental aspects of this receptor and the downstream signal transduction pathway are conserved in bacteria and higher eukaryotic mitochondria. The alpha-3 subdivision of the purple bacteria is considered to be a likely source of the endosymbiont that ultimately gave rise to the mitochondrion. Therefore, it is possible that the mammalian PBR remains both evolutionarily and functionally related to the TspO of R. sphaeroides.
Glutamate-cysteine ligase catalytic subunit (GCS)
Type: Family

This family represents the catalytic subunit of glutamate-cysteine ligase (

), also known as gamma-glutamylcysteine synthetase (GCS). This enzyme catalyses the rate limiting step in the biosynthesis of glutathione. The eukaryotic enzyme is a dimer of a heavy chain and a light chain with all the catalytic activity exhibited by the heavy chain.
Equine arteritis virus Gp3 (EAV_Gp3)
Type: Family

This entry contains proteins encoded by ORF3 of Equine arteritis virus. They are possible envelope glcoproteins.
Vacuolating cytotoxin, putative (Vacuolating_cytotoxin_put)
Type: Domain

Proteins containing this domain include a number of Helicobacter pylori outer membrane proteins with multiple copies of this small conserved region.
Arabidopsis retrotransposon Orf1, C-terminal (ATHILA_Orf1_C)
Type: Domain

ATHILA is a group of Arabidopsis thaliana retrotransposons belonging to the Ty3/gypsy family of the long terminal repeat (LTR) class of eukaryotic retrotransposons . The central region of ATHILA retrotransposons contains two or three open reading frames (ORFs). This entry represents the C-terminal domain of the ORF1 product. The function of ORF1 is unknown.
Acireductone dioxygenase ARD family (ARD)
Type: Family

The two acireductone dioxygenase enzymes (ARD and ARD', previously known as E-2 and E-2') from Klebsiella pneumoniae share the same amino acid sequence

, but bind different metal ions: ARD binds Ni2+, ARD' binds Fe2+ . ARD and ARD' can be experimentally interconverted by removal of the bound metal ion and reconstitution with the appropriate metal ion. The two enzymes share the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, but yield different products. ARD' yields the alpha-keto precursor of methionine (and formate), thus forming part of the ubiquitous methionine salvage pathway that converts 5'-methylthioadenosine (MTA) to methionine. This pathway is responsible for the tight control of the concentration of MTA, which is a powerful inhibitor of polyamine biosynthesis and transmethylation reactions . ARD yields methylthiopropanoate, carbon monoxide and formate, and thus prevents the conversion of MTA to methionine. The role of the ARD catalysed reaction is unclear: methylthiopropanoate is cytotoxic, and carbon monoxide can activate guanylyl cyclase, leading to increased intracellular cGMP levels .
Neprosin (Neprosin)
Type: Domain

Pitcher plants are insectivorous and secrete a digestive fluid into the pitcher. This fluid contains a mixture of enzymes including peptidases. One of these is Neprosin, characterised from the pitcher plant Nepenthes ventrata. This is a glutamic endopeptidase that preferentially cleaves peptide bonds on the C-terminal side of proline residues . It also cleaves peptide bonds on the C-terminal side of alanine residues but with less efficiency . The peptidase is secreted and is presumed to possess an N-terminal activation peptide. The Neprosin domain corresponds to the mature peptidase .
Male Drosophila accessory gland secretory protein (Male_ac_gland_sc)
Type: Family

The accessory gland of male insects is a genital tissue that secretes many components of the ejaculatory fluid, some of which affect the female's receptivity to courtship and her rate of oviposition. The protein is expressed exclusively in the male accessory glands of adult Drosophila melanogaster. During copulation it is transferred to the female genital tract where it is rapidly altered .
Sugar transporter SWEET repeat (SWEET_rpt)
Type: Repeat

This entry includes Sugar Will Eventually be Exported Transporters (SWEETs) which are specific sugar efflux transporters essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development . They can carry mono- and disaccharides across a membrane following the concentration gradient. In many organisms it mediates glucose transport ; in Arabidopsis it is necessary for pollen viability; and two of the rice homologues are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter . Homologues of SWEETs have been identified in bacteria .

The founding member of the SWEET family, formerly known as MtN3 and saliva in Drosophila, was identified as a nodulin-specific EST in the legume Medicago truncatula . Human SWEET1 is also known as RAG1-activating protein 1 as it has been described to be involved in activation and expression of recombination activation genes (RAGs) .
Sigma1/sigma2, reoviral (Sigma_1_2_reovir)
Type: Family

Reoviruses are double-stranded RNA viruses that lack a membrane envelope. Their capsid is organised in two concentric icosahedral layers: an inner core and an outer capsid layer. The sigma1 protein is found in the outer capsid, and the sigma2 protein is found in the core. There are four other kinds of protein (besides sigma2) in the core, termed lambda 1-3, mu2. Interactions between sigma2 and lambda 1 and lambda 3 are thought to initiate core formation, followed by mu2 and lambda2 .
Rhoptry-associated protein 1 (RAP-1)
Type: Family

Members of this family are found in the parasite Babesia bigemina. Other rhoptry-associated proteins are found in Plasmodium falciparum but these do not belong to this family. Animal infection with B. bigemina may produce a pattern similar to human malaria . Rhoptry organelles form part of the apical complex in apicomplexan parasites.
Domain of unknown function DUF240 (DUF240)
Type: Domain

This is a domain of unknown function found in mycoplasma. It is found at the N-terminal region.
Protein BPS1, chloroplastic (BPS1_pln)
Type: Family

This family includes BPS1 (Protein BYPASS 1) from plants, a protein required for normal root and shoot development. It prevents constitutive production of a root mobile carotenoid-derived signalling compound that is capable of arresting shoot and leaf development .