SII-SWORD/CoKE huggingface dataset:
tRNA (guanine-N-7) methyltransferase, Trmb type (tRNA_(Gua-N-7)_MeTrfase_Trmb)
Type: Family

This entry represents tRNA (guanine-N-7) methyltransferase (

), which catalyses the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. Capping of the pre-mRNA 5' end by addition a monomethylated guanosine cap (m(7)G) is an essential and the earliest modification in the biogenesis of mRNA . The reaction is catalysed by three enzymes: triphosphatase, guanylyltransferase, and tRNA (guanine-N-7) methyltransferase . This entry includes Bacillus subtilis TrmB, which contains a unique variant of the Rossmann-fold methyltransferase (RFM) structure, with the N-terminal helix folded on the opposite site of the catalytic domain .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Photosystem I Ycf4, assembly (PSI_Ycf4_assembly)
Type: Family

Photosystem I (PSI) is a large protein complex embedded within the photosynthetic thylakoid membrane formed by a core complex, peripheral light-harvesting complexes (LHCIs) and cofactors. It consists of 15 core and 4 LHCI subunits, ~150 chlorophylls (a and b) molecules, 2 phylloquinones, and 3 Fe4S4-clusters . The three dimensional structure of the PSI complex has been resolved at 2.5 A , which allows the precise localisation of each cofactor. PSI together with photosystem II (PSII) catalyses the light-induced steps in oxygenic photosynthesis - a process found in cyanobacteria, eukaryotic algae (e.g. red algae, green algae) and higher plants.

To date, three thylakoid proteins involved in the stable accumulation of PSI have been identified: BtpA (

) , Ycf3 , and Ycf4 . Because translation of the psaA and psaB mRNAs encoding the two reaction centre polypeptides, of PSI and PSII respectively, is not affected in mutant strains lacking functional ycf3 and ycf4, the products of these two genes appear to act at a post-translational step of PSI biosynthesis. The BtpA protein appears to act at the level of PSI stabilisation . It is an extrinsic membrane protein located on the cytoplasmic side of the thylakoid membrane . Homologs of BtpA are found in the crenarchaeota and euryarchaeota, where their function remains unknown. The Ycf4 protein is firmly associated with the thylakoid membrane, presumably through a transmembrane N-terminal domain . Together with Ycf3, it forms a core PSI assembly apparatus as an auxiliary factor. The Ycf3 is a TPR-containing protein loosely associated with the thylakoid membrane and, with its interacting partner Y3IP1, facilitates the assembly of reaction centre subunits. Ycf4 facilitates the integration of peripheral PSI subunits and LHCIs into the PSI reaction centre subcomplex .
US22-like (US22-like)
Type: Family

Herpesviruses are large and complex DNA viruses, widely found in nature. Human cytomegalovirus (HCMV), an important human pathogen, defines the betaherpesvirus family. Mouse cytomegalovirus (MCMV) and rat cytomegalovirus serve as biological model systems for HCMV. HCMV, MCMV, and rat CMV display the largest genomes among the herpesviruses and are essentially co-linear over the central 180 kb of the 230-kb genomes. Betaherpesviruses, which include the CMVs as well as human herpesviruses 6 and 7, differ from alpha- and gammaherpesviruses by the presence of additional gene families such as the US22 gene family, which are mainly clustered at the ends of the genome. The US22 family was first described in HCMV. This gene family comprises 12 members in both HCMV and MCMV and 11 in rat CMV .

US22 proteins have been found across many animal DNA viruses and some vertebrates . The name sake of this family US22 (

) is an early nuclear protein that is secreted from cells . The US22 family may have a role in virus replication and pathogenesis . Domain analysis showed that US22 proteins usually contain two copies of conserved modules which is homologous to several other families like SMI1 and SYD (commonly called SUKH superfamily). Bacterial operon analysis revealed that all bacterial SUKH members function as immunity proteins against various toxins. Thus US22 family is predicted to counter diverse anti-viral responses by interacting with specific host proteins .

This family also includes G2/M cell-cycle inhibitor DR6 and DR7 that are known to inhibit the host G2/M cell-cycle progression in a p53-independent manner .
Acetaldehyde dehydrogenase (Acetaldehyde_dehydrogenase)
Type: Family

The acetaldehyde dehydrogenase family (

) of bacterial enzymes catalyse the formation of acetyl-CoA from acetaldehyde in the 3-hydroxyphenylpropinoate degradation pathway. It occurs as a late step in the meta-cleavage pathways of a variety of compounds, including catechol, biphenyl, toluene, salicylate .

Members of this entry heterodimerise with members of

to form a bifunctional aldolase-dehydrogenase .

Members of this protein family are acetaldehyde dehydrogenase (acetylating),

. This enzyme oxidizes acetaldehyde, using NAD(+), and attaches coenzyme A (CoA), yielding acetyl-CoA., etc.
Bacterial sugar transferase (Bact_transf)
Type: Domain

This entry represents a conserved region from a number of different bacterial sugar transferases, involved in diverse biosynthesis pathways. Examples include galactosyl-P-P-undecaprenol synthetase (

), which transfers galatose-1-phosphate to the lipid precursor undecaprenol phosphate in the first steps of O-polysaccharide biosynthesis; UDP-galactose-lipid carrier transferase, which is involved in the biosynthesis of amylovoran; and galactosyl transferase CpsD, which is essential for assembly of the group B Streptococci (GBS) type III capsular polysaccharide.
CUB-like domain (CUB-like_dom)
Type: Domain

This domain is found in a family of hypothetical Caenorhabditis elegans proteins. The aligned region has no known function nor do any of the proteins which possess it. However, this domain is related to the CUB domain (

). The aligned region is approximately 130 amino acids long and contains two conserved cysteine residues.
Thrombospondin, type 3-like repeat (Thrombospondin_3-like_rpt)
Type: Repeat

The thrombospondin repeat is a short aspartate rich repeat which binds to calcium ions. The repeat was initially identified in thrombospondin proteins that contained 7 of these repeats . The repeat lacks defined secondary structure .

This entry represents the type 3 thrombospondin repeat found in proteins of the thrombospondin family and related repeats present in other types of proteins.
Polymorphic outer membrane protein repeat (POMP_repeat)
Type: Repeat

This repeat is found in several Chlamydia polymorphic membrane proteins . Chlamydia pneumoniae (Chlamydophila pneumoniae) is an obligate intracellular bacterium and a common human pathogen causing infection of the upper and lower respiratory tract. Proteins in this entry consist of there repeats at the N-terminal which may adopt a β-helical structure, a middle domain (

) and a C-terminal domain

.
Sec-independent protein translocase protein TatA/B/E (TatA/B/E)
Type: Family

Translocation of proteins across the two membranes of Gram-negative bacteria can be carried out via a number of routes. Most proteins marked for export carry a secretion signal at their N terminus, and are secreted by the general secretory pathway. The signal peptide is cleaved as they pass through the outer membrane. Other secretion systems include the type III system found in a select group of Gram-negative plant and animal pathogens, and the CagA system of Helicobacter pylori .

In some bacterial species, however, there exists a system that operates independently of the Sec pathway . It selectively translocates periplasmic-bound molecules that are synthesised with, or are in close association with, "partner" proteins bearing an (S/T)RRXFLK twin arginine motif at the N terminus. The pathway is therefore termed the Twin-Arginine Translocation or TAT system. Surprisingly, the four components that make up the TAT system are structurally and mechanistically related to a pH-dependent import system in plant chloroplast thylakoid membranes . The gene products responsible for the Sec-independent pathway are called TatA, TatB, TatC and TatE.

This entry represents the related TatA, TatB and TatE proteins.
Chromate transporter (Chromate_transpt)
Type: Family

This entry represents chromate transporters (CHR) . These proteins reduce chromate accumulation and are essential for chromate resistance. They are composed of one or two copies of this region. The short-chain CHR proteins (such as YwrB and YwrA) form heterodimer transporters which efflux chromate ions from the cytoplasm, while the long chain CHR proteins appear to have arisen from a gene fusion event of two short chain transporters.
Photosystem II PsbL (PSII_PsbL)
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 .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This entry represents the low molecular weight transmembrane protein PsbL found in PSII. PsbL is located in a gene cluster with PsbE, PsbF and PsbJ (PsbEFJL). Both PsbL and PsbJ (

) are essential for proper assembly of the OEC. Mutations in PsbL prevent the formation of both PSII core dimers and PSII-light harvesting complex . In addition, both PsbL and PsbJ are involved in the unidirectional flow of electrons, where PsbJ regulates the forward electron flow from D2 (Qa) to the plastoquinone pool, and PsbL prevents the reduction of PSII by back electron flow from plastoquinol protecting PSII from photo-inactivation .
Ferrous iron transport protein B (Fe2_transport_prot-B)
Type: Family

Escherichia coli has an iron(II) transport system (feo) which may make an important contribution to the iron supply of the cell under anaerobic conditions. FeoB has been identified as part of this transport system and may play a role in the transport of ferrous iron. FeoB is a large 700-800 amino acid integral membrane protein. The N terminus contains a P-loop motif suggesting that iron transport may be ATP dependent .
ApbE-like superfamily (ApbE-like_sf)
Type: Homologous_superfamily

This superfamily previously known as ApbE (thought to be involved in thiamine biosynthesis, alternatively known as Mg2+-dependent flavin transferase that has a role in catalysing the covalent attachment of FMN to a threonine residue in bacterial flavoproteins ) was renamed to Ftp (flavin-trafficking protein) in 2013 due to the characterisation of TP0796, a lipoprotein from T. pallidum, which is classified as a putative member of the ApbE superfamily (

).
FAD pyrophosphatase (

) catalyses the hydrolysis of FAD, forming AMP and FMN. To date, the Ftp (TP0796) of T. pallidum is the first bacterial FAD pyrophosphatase shown to have a strict requirement for Mg2+ for its catalytic activity. Other Ftp homologs (formerly known as ApbE proteins) are present in the genomes of numerous bacteria and in lower eukaryotes, such as Trypanosoma spp. (agents of sleeping sickness and Chagas disease) and Leishmania spp. (agent of leishmaniasis), but the eukaryotic homologs appear to be fused with a multidomain fumarate reductase.

Other members of the ApbE superfamily are related to the periplasmic ApbE lipoprotein of Salmonella typhimurium. In S. typhimurium, ApbE has been shown to be involved in thiamine biosynthesis and may serve in the conversion of aminoimidazole ribotide to 4-amino-5-hydroxymethyl-2-methylpyrimidine. T. pallidum is predicted to lack the thiamine pathway as well as the enzymes involved in aminoimidazole ribotide metabolism. The periplasmic location of ApbE prompts questions concerning how it could participate in a cytoplasmic pathway. ApbE proteins are relatively understudied biochemically, and representative crystal structures (PDB entries

and

) have failed to definitively elucidate their functions.

Some studies have shown that some of the Ftp family proteins bind FAD and that the Ftp protein from Vibrio harveyi transfers the FMN portion of FAD to a subunit of the integral inner membrane Nqr redox pump. The crystal structure of Ftp from T. pallidum displays a highly conserved Ftp fold and an active site/FAD-binding site of all known Ftp-like proteins.
Photosystem I PsaE, reaction centre subunit IV (PSI_PsaE)
Type: Family

PsaE is a 69 amino acid polypeptide from photosystem I present on the stromal side of the thylakoid membrane. The structure is comprised of a well-defined five-stranded β-sheet similar to SH3 domains . This subunit may form complexes with ferredoxin and ferredoxin-oxidoreductase in the photosystem I reaction centre.
Peridinin-chlorophyll A binding protein (Peridinin-chlorophyll-bd_prot)
Type: Family

Peridinin-chlorophyll-protein, a water-soluble light-harvesting complex that has a blue-green absorbing carotenoid as its main pigment, is present in most photosynthetic dinoflagellates. These proteins are composed of two similar repeated domains. These domains constitute a scaffold with pseudo-twofold symmetry surrounding a hydrophobic cavity filled by two lipid, eight peridinin, and two chlorophyll a molecules .
Cornichon (Cornichon)
Type: Family

This entry represents a group of conserved proteins from fungi, plants to animals. They are transmembrane proteins. Proteins in this entry include budding yeast Erv14/15, Drosophila Cornichon and human CNIH1/2/3/4.
Fringe-like, glycosyltransferase domain (Fringe-like_glycosylTrfase)
Type: Domain

This entry represents the glycosyltransferase domain found in fringe proteins from Drosophila and its orthologues from mammals LFNG/RFNG/DFNG and glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1).

The Notch receptor is a large, cell surface transmembrane protein involved in a wide variety of developmental processes in higher organisms . It becomes activated when its extracellular region binds to ligands located on adjacent cells. Much of this extracellular region is composed of EGF-like repeats, many of which can be O-fucosylated. A number of these O-fucosylated repeats can in turn be further modified by the action of a beta-1,3-N-acetylglucosaminyltransferase enzyme known as Fringe . Fringe potentiates the activation of Notch by Delta ligands, while inhibiting activation by Serrate/Jagged ligands. This regulation of Notch signalling by Fringe is important in many processes .

Four distinct Fringe proteins have so far been studied in detail; Drosophila Fringe (Dfng) and its three mammalian homologues Lunatic Fringe (Lfng), Radical Fringe (Rfng) and Manic Fringe (Mfng). Dfng, Lfng and Rfng have all been shown to play important roles in developmental processes within their host, though the phenotype of mutants can vary between species e.g. Rfng mutants are retarded in wing development in chickens, but have no obvious phenotype in mice . Mfng mutants have not, so far, been charcterised. Biochemical studies indicate that the Fringe proteins are fucose-specific transferases requiring manganese for activity and utilising UDP-N-acetylglucosamine as a donor substrate . The three mammalian proteins show distinct variations in their catalytic efficiencies with different substrates.

Dfng is a glucosaminyltransferase that controls the response of the Notch receptor to specific ligands which is localised to the Golgi apparatus (not secreted as previously thought). Modification of Notch occurs through glycosylation by Dfng.
Carboxylase, conserved domain (Carboxylase_cons_dom)
Type: Domain

This domain represents a conserved region in pyruvate carboxylase (PYC) (

), oxaloacetate decarboxylase alpha chain (OADA) (

), and transcarboxylase 5s subunit (

). The domain is found adjacent to the HMGL-like domain (

) and often close to the biotin_lipoyl domain (

) of biotin requiring enzymes.
SKI/SNO/DAC domain (SKI/SNO/DAC)
Type: Domain

This domain is about 100 amino acids long and contains a conserved CLPQ motif. The c-ski proto-oncogene has been shown to influence proliferation, morphological transformation and myogenic differentiation . Sno, a Ski proto-oncogene homologue, is expressed in two isoforms and plays a role in the response to proliferation stimuli. Dachshund also contains this domain. It is involved in various aspects of development .
Shutoff protein L4 (L4)
Type: Family

The late 100kDa protein (also known as L4) inhibits host translation while promoting late viral translation by ribosome shunting . It blocks host cap-dependent translation by binding to eIF4G, displacing MKNK1 from cap initiation complexes and preventing EIF4E phosphorylation .
Flavoprotein (Flavoprotein)
Type: Domain

This entry contains a diverse range of flavoprotein enzymes, including epidermin biosynthesis protein, EpiD, which has been shown to be a flavoprotein that binds FMN . This enzyme catalyzes the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond. This family also includes the B chain of dipicolinate synthase a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance . Dipicolinate synthase catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid. This family also includes phenylacrylic acid decarboxylase

and phosphopantothenoylcysteine decarboxylase HAL3

.
Circovirus capsid protein (Circovirus_capsid)
Type: Family

Circoviruses are small circular single stranded viruses. This family is the capsid protein from viruses such as Porcine circovirus and Beak and feather disease virus

.
Hepatitis E virus Orf2, capsid (HEV_Orf2)
Type: Family

The Hepatitis E virus(HEV) genome is a single-stranded, positive-sense RNA molecule of approximately 7.5 kb . Three open reading frames (ORF) were identified within the HEV genome: ORF1 encodes nonstructural proteins, ORF2 encodes the putative structural protein(s), and ORF3 encodes a protein of unknown function. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins .
Glycoside hydrolase, family 77 (Glyco_hydro_77)
Type: Family

4-alpha-glucanotransferases (

) belong to the glycoside hydrolase family 77

. They transfer a segment of a (1,4)-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or (1,4)-alpha-D-glucan . 4-alpha-glucanotransferases from prokaryotes are known as amylomaltases and those from plants, including algae, are known as disproportionating enzymes (DPE). Both belong to the disproportionating family .
Lecithin:cholesterol/phospholipid:diacylglycerol acyltransferase (LACT/PDAT_acylTrfase)
Type: Family

This entry represents a group of lipid metabolizing enzymes, including LACT and LPLA2 from humans, and PDAT from plants.

Lecithin:cholesterol acyltransferase (LACT), also known as phosphatidylcholine-sterol acyltransferase (

), is involved in extracellular metabolism of plasma lipoproteins, including cholesterol. It esterifies the free cholesterol transported in plasma lipoproteins, and is activated by apolipoprotein A-I. Its structure has been revealed . Defects in LACT cause Fish eye disease and familial LCAT deficiency .

Phospholipid:diacylglycerol acyltransferase (PDAT)(

) is involved in triacylglycerol formation by an acyl-CoA independent pathway. The enzyme specifically transfers acyl groups from the sn-2 position of a phospholipid to diacylglycerol, thus forming an sn-1-lysophospholipid .

Lysosomal phospholipase A2 (LPLA2) (

) plays important roles for lung surfactant metabolism and maturation of invariant natural killer T cells. Its structure has been revealed .
Nodulin (Nodulin)
Type: Family

Nodulin is a plant protein of unknown function. It is induced during nodulation in legume roots after rhizobium infection.
Reticulon (Reticulon)
Type: Domain

Eukaryotic proteins of the reticulon (RTN) family all share an association with the endoplasmic reticulum (ER). Whereas amino-terminal regions are not related to one another, all reticulon proteins share a 200 amino acid residue region of sequence similarity at the C-terminal. This region contains two large hydrophobic regions separated by a 66 residue hydrophilic segment. The conserved hydrophobic C-terminal portion has been shown to play an essential role in the association of reticulons with the ER membrane. The hydrophobic portions are supposed to be membrane-embedded and the hydrophilic 66 residue localized to the lumenal/extracellular face of the membrane. Most reticulons have a di-lysine ER retention motif at the C-terminal. Because of their likely association with the rough as well as the smooth ER, the reticulons might play some role in transport processes or in regulation of intracellular calcium levels. It has been suggested that the reticulons may be serving as ER-associated channel-like complexes .
Adenovirus packaging protein 1 (Adeno_IVa2)
Type: Family

Packaging protein 1 (also known as IVa2) is a component of the packaging machinery which encapsidates the viral DNA into preformed capsids and transcriptional activator of the viral major late promoter (MLP) . It binds, along with packaging proteins 2 and 3, to the specific packaging sequence on the left end of viral genomic DNA and displays ATPase activity thereby providing the power stroke of the packaging machinery .