SII-SWORD/CoKE huggingface dataset:
Uncharacterised protein family UPF0128 (UPF0128)
Type: Family

The function of this family is unknown. These proteins are from 222 to 233 residues in length, lack hydrophobic stretches, and are found predominantly in thermophiles.
Glycerol-3-phosphate transporter (G3P_transporter)
Type: Family

This family includes very hydrophobic proteins, predicted to span the membrane at least 8 times. The two members confirmed experimentally as glycerol-3-phosphate transporters, from Escherichia coli and Bacillus subtilis , share more than 50 % amino acid identity.
Conserved hypothetical protein CHP00725 (CHP00725)
Type: Family

This family of conserved hypothetical proteins has no known function.
Cytokinin riboside 5'-monophosphate phosphoribohydrolase LOG (LOG)
Type: Family

This entry represents a cytokinin-activating enzyme working in the direct activation pathway. It is a phosphoribohydrolase that converts inactive cytokinin nucleotides to the biologically active free-base forms . The proteins in this entry belong to the LOG family of proteins.
tRNA-dihydrouridine synthase, TIM-barrel, NifR3-related (tRNA_dU_NifR3-rel)
Type: Family

The function of this family is unknown, but it may include TIM-barrel proteins.
Carboxy-S-adenosyl-L-methionine synthase (CmoA)
Type: Family

This family represents the carboxy-S-adenosyl-L-methionine synthase CmoA. CmoA and CmoB are important components of the cmo5U biosynthetic pathway. These enzymes are involved in the conversion of 5-methoxyuridine (mo5U) to uridine-5-oxyacetic acid (cmo5U) at the wobble position (34) of tRNA . Uridine-5-oxyacetic acid at tRNA position 34 is apparently necessary for the efficient decoding of G-ending Pro, Ala, and Val codons in these organisms . cmo5U modification requires the previously unknown metabolite carboxy-S-adenosine-L-methionine (Cx-SAM), which is generated by CmoA through conversion of prephenate and SAM to yield Cx-SAM and phenylpyruvate .
Protein of unknown function DUF406 (DUF406)
Type: Family

These small proteins are approximately 100 amino acids in length and appear to be found only in gamma proteobacteria. The function of this protein family is unknown .
Uracil-DNA glycosylase family 4 (Ura-DNA_glyco_family4)
Type: Domain

Uracil-DNA glycosylase (UDG) removes uracil from DNA to initiate DNA base excision repair. UDGs were classified into families 1, 2 and 3 on the basis of sequence similarity. Thermophilic UDGs have been identify more recently and they have been classified as a new UDG family, family 4 .

The enzymes of family 4 Uracil-DNA glycosylase (UDG), found in thermophilic organisms, are thermostable enzymes. Uracil-DNA glycosylases (UDGs) are DNA repair enzymes that catalyze the removal of mismatched uracil from DNA to initiate DNA base excision repair pathway. The Thermus thermophilus enzyme TTUDGA removes uracil from both, ssDNA and dsDNA, but not thymine from a G:T mismatch . These details suggest that the mechanism by which Family 4 UDGs remove uracils from DNA is similar to that of Family 1 enzymes . The thermostability of the enzyme may be linked to the presence of an iron-sulfur cluster, salt-bridges and ion pairs on the molecular surface as well as prolines on loops and turns, as commonly found in the Family 4 enzymes.

Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. Uracil mispaired with guanine in DNA is one of the major pro-mutagenic events, causing G:C->A:T mutations .
Inner membrane protein YhjD (IM_pro_YhjD)
Type: Family

This family, including YhjD in E. coli, is a conserved inner membrane protein . Its homologue, YihY, was incorrectly assigned to be ribonuclease BN previously .
L-fucose-proton symporter FucP (Lfuc_symporter_FucP)
Type: Family

This family describes the L-fucose-proton symporter (also known as L-fucose permease) in bacteria, which mediates the uptake of L-fucose across the boundary membrane with the concomitant transport of protons into the cell . L-fucose(6-deoxy-L-galactose) is a monosaccharide found in glycoproteins and cell wall polysaccharides. L-fucose is used in bacteria through an inducible pathway mediated by at least four enzymes: a permease, isomerase, kinase and an aldolase which are encoded by fucP, fucI, fucK, fucA respectively.
Uncharacterised protein family, Major Facilitator Superfamily MSF4 (Uncharacterised_MSF4)
Type: Family

The MFS is a very old, large and diverse superfamily that includes several hundred sequenced members. They catalyze uniport, solute:cation (H+ or Na+) symport and/or solute:H+ or solute:solute antiport. Most are of 400-600 amino acyl residues in length and possess either 12 or 14 putative transmembrane a-helical spanners. They exhibit specificity for sugars, polyols, drugs, neurotransmitters, Krebs cycle metabolites, phosphorylated glycolytic intermediates, amino acids, peptides, osmolites, nucleosides, organic anions, inorganic anions, etc. They are found ubiquitously in all three kingdoms of living organisms. The generalized transport reactions catalyzed by MFS porters are:

(1)Uniport: S (out) S (in).

(2)Symport: S (out) + [H+ or Na+] (out) --->S (in) + [H+ or Na+] (in).

(3)Antiport: S1 (out) + S2 (in) S1 (in) + S2 (out), (S1 may be H+ or a solute)

This family of proteins are uncharacterised proteins from archaea, which may be major facilitators. This family includes proteins from Archaeoglobus fulgidus and Aeropyrum pernix.
Dipeptide/tripeptide permease (Dipep/tripep_permease)
Type: Family

This entry includes dipeptide and tripeptide transporters belonging to the proton-dependent oligopeptide transporter (POT) family, also called the peptide transport (PTR) family.

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The amino acid/peptide transporter family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analysis of a number of recently discovered peptide transport proteins . This family consists of bacterial proton-dependent oligopeptide transporters, although they are found in yeast, plants and animals. They function by proton symport in a 1:1 stoichiometry, which is variable in different species. Structurally, these transporters present a conserved architecture consisting of 14 transmembrane α-helices with N-terminal and C-terminal six-helix bundles connected by two transmembrane α-helices (HA and HB) .
Homoserine kinase, type II (Homoserine_kinase_II)
Type: Family

This family is composed of unusual homoserine kinases, from a subset of bacteria, which have a protein kinase fold. These proteins do not bear any similarity to the GHMP family homoserine kinases (see

) present in most bacteria and eukaryotes. Homoserine kinase catalyzes the transfer of the gamma-phosphoryl group from ATP to L-homoserine producing L-homoserine phosphate, an intermediate in the production of the amino acids threonine, methionine, and isoleucine. The Type II homoserine kinase subfamily is part of a larger superfamily that includes the catalytic domains of other kinases, such as the typical serine/threonine/tyrosine protein kinases (PKs), RIO kinases, actin-fragmin kinase (AFK), and phosphoinositide 3-kinase (PI3K) .
Monovalent cation:proton antiporter, subunit B (CPA3_sub_B)
Type: Family

This family of proteins consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterised systems are the PhaABCDEFG system of Rhizobium meliloti which functions in pH adaptation and as a K+ efflux system and the MnhABCDEFG system of Staphylococcus aureus which functions as a Na+:H+ antiporter.This family is specific for the phaB and mnhB proteins.
Lysosomal cystine transporter (LC_transporter)
Type: Family

Members of this family belong to the cystinosin family and are integral membrane lysosomal proteins and they are thought to transport cystines out of lysosomes. Protein ERS1 has been characterised and encodes a functional homologue of the human lysosomal cystine transporter .
Peroxysomal long chain fatty acyl transporter (FA_transporter)
Type: Family

Eukaryotic ABC transporters are found either as complete transporters or as half transporters, which dimerise to form an active transporter. Four half ABC transporter proteins have been identified in the human peroxisome membrane: the 70kDa peroxisomal membrane protein (PMP70), the adrenoleukodystrophy protein (ALDP), the PMP70-related protein (P70R) and the ALDP-related protein (ALDR) . This entry includes PMP70 (renamed as ATP-binding cassette sub-family D member 3, ABCD3) and ALDP (ATP-binding cassette sub-family D member 1, ABCD1) from human, and yeast peroxisomal long-chain fatty acid import proteins PAT1 (PXA2) and PAT2 (PXA1) .

The members of this family are involved in the import of activated long-chain fatty acids from the cytosol to the peroxisomal matrix.
Pigment precursor permease/Protein ATP-binding cassette sub-family G (Pigment_permease/Abcg)
Type: Family

This family includes pigment precursor permeases (protein white, brown and scarlet) from flies and ATP-binding cassette sub-family G member 1 (ABCG1) from mammals.
Pleiotropic drug resistance protein PDR/CDR (Drug-R_PDR/CDR)
Type: Family

This family consists of multidrug resistance ATP binding cassette (ABC) transporters from fungi. This family includes PDR10 and PDR15, members of the pleiotropic drug resistance (PDR) network in Saccharomyces cerevisiae , and CDR transporters from Candida albicans .

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .
Conserved hypothetical protein CHP00375 (CHP00375)
Type: Family

This family of conserved hypothetical proteins has no known function.
L-aspartate oxidase (NadB)
Type: Family

L-aspartate oxidase is the B protein, NadB, of the quinolinate synthetase complex. Quinolinate synthetase makes a precursor of the pyridine nucleotide portion of NAD.
Small ribosomal subunit protein uS15, bacterial-type (Ribosomal_uS15_bac-type)
Type: Family

This family includes specifically bacterial, chloroplast, and mitochondrial ribosomal protein uS15.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Antigen peptide transporter 2 (Tap2/ABCB3)
Type: Family

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .

This entry represents Tap2 (also known as antigen peptide transporter 2), which is an eukaryotic protein belonging to the ABC transporter family. It plays a crucial role in the processing and presentation of the MHC class I-restricted antigens. It is a half transporter that forms a complex with Tap1. This complex translocates antigens from the cytoplasm to the endoplasmic reticulum for loading onto MHC class I molecules .
ATP synthase, F1 complex, alpha subunit (ATP_synth_F1_asu)
Type: Family

This entry represents the alpha subunit found in the F1 complex of F-ATPases. 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-subunit contains a highly conserved adenine-specific non-catalytic nucleotide-binding domain, with a conserved amino acid sequence of Gly-X-X-X-X-Gly-Lys. 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 is driven by the movement of protons through the F0 complex C subunit .

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.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.
IBV 3B protein (IBV_3B)
Type: Family

These proteins are the product of ORF 3B from Infectious bronchitis virus). Currently, the function of this protein remains unknown .
IBV 3C protein (IBV_3C)
Type: Family

These proteins are the product of ORF 3C from Infectious bronchitis virus. Currently, the function of this protein remains unknown.
Lipoprotein repeat (Lipoprotein_repeat)
Type: Repeat

This repeat is found in tandem in a set of lipoproteins. The alignment contains a Y-X4-D motif.
MAP domain (MAP_dom)
Type: Domain

Map (MHC class II analogous protein), also known as eap (extracellular adherence protein) and p70, is found in Staphylococcus aureus. It is a cell-wall associated protein, which is capable of binding to a number of different extracellular matrix glycoploteins and plasma proteins, and to the cell surface of S. aureus. Besides the broad binding specificity, map has been shown to be important in the adherence to and internalization of S. aureus by eukaryotic cells as well as being capable of modulating inflammatory response through its interactions with ICAM-1 (intercellular adhesion molecule-1), although its biological role in vivo remains to date unclear .

The protein consists of a signal peptide followed by a unique sequence of about 20 amino acids and four to six repeated MAP domains of 110-amino acid residues. Within each repeat there is a subdomain consisting of 31 residues that was found to be highly homologous to the N-terminal beta-chain of many MHC class II molecules .

This entry represents the MAP domain. The crystal structure of this domain has been solved and shows a core fold that is comprised of an α-helix lying diagonally across a five-stranded, mixed β-sheet. This structure is very similar to the C-terminal domain of bacterial superantigens .
SAM dependent carboxyl methyltransferase (MeTrfase_7)
Type: Family

This family of plant methyltransferases contains enzymes that act on a variety of substrates including salicylic acid, jasmonic acid and 7-methylxanthine. Caffeine is synthesised through sequential three-step methylation of xanthine derivatives at positions 7-N, 3-N, and 1-N . The protein 7-methylxanthine methyltransferase (designated as CaMXMT) catalyses the second step to produce theobromine . The protein Carlactonoate CLA methyltransferase (CLAMT) catalyses the biosynthesis of (11R)-methyl carlactonoate from (11R)-carlactonoate .
Lytic transglycosylase MltA, domain B (MltA_B)
Type: Domain

Escherichia coli MltA is a membrane-bound lytic transglycosylase comprised of two domains separated by a large groove, where the peptidoglycan strand binds. Domain A is made up of an N-terminal and a C-terminal portion, which correspond to the 3D domain, named for 3 conserved aspartate residues. Domain B is inserted within the linear sequence of domain A .

MltA is a membrane-bound, murein degrading transglycosylase enzyme that plays an important role in the controlled growth of the stress-bearing sacculus of E. coli .
MOB kinase activator family (MOB_kinase_act_fam)
Type: Family

The MOB kinase activator family includes MOB1, an essential Saccharomyces cerevisiae protein, identified from a two-hybrid screen, that binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Conditional alleles of MOB1 cause a late nuclear division arrest at restrictive temperature . This family also includes the MOB-like protein phocein, an intracellular protein that interacts with striatin and may play a role in membrane trafficking .
Molybdenum cofactor sulfurase, C-terminal (MoCF_Sase_C)
Type: Domain

Molybdenum cofactor (MOCO) sulphurases catalyse the insertion of a terminal sulphur ligand into the molybdenum cofactor, thereby converting the oxo form of MOCO to a sulphurylated form. Suphurylated MOCO is required by several enzymes, including: aldehyde oxidase (

), which function in the last step of abscisic acid biosynthesis in plants ; and xanthine dehydrogenase (

), which synthesis uric acid from xanthine during nitrogen metabolism .

This entry represents the β-barrel C-terminal domain of MOCO sulphurase (MOSC domain), which has a β-barrel structure similar to that of the β-barrel domain in pyruvate kinase and contains a highly conserved cysteine residue required for activity. MOSC domains are found in several diverse metal-sulphur cluster biosynthesis proteins from both eukaryotes and prokaryotes. MOSC domains occur as either stand-alone forms, such as the YiiM protein from Escherichia coli, or fused to other domains, such as a NifS-like catalytic domain in MOCO sulphurase. The MOSC domain is predicted to be a sulphur-carrier domain that receives sulphur abstracted from pyridoxal phosphate-dependent NifS-like enzymes, on its conserved cysteine, and delivers it for the formation of diverse sulphur-metal clusters .

The MOSC domain contains several patches of hydrophobic residues and an absolutely conserved cysteine residue situated closer to the C-terminal end of the domain. The absolutely conserved cysteine in the MOSC domain is reminiscent of the analogous conservation of a cysteine in the active site of the thioredoxin and rhodanese superfamilies. Members of both these superfamilies, especially of the latter one, have been implicated in the synthesis of Fe-S clusters, through mobilisation of sulphur with their active cysteine.
Molybdenum cofactor sulfurase, middle domain (MOCOS_middle)
Type: Domain

This entry represents a domain located in the middle of Molybdenum cofactor sulfurases (MOCOS). MOCOS sulfurates the molybdenum cofactor . Mutations in this protein lead to a disorder characterised by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones .

This domain is also found at the N-terminal end of Mitochondrial amidoxime-reducing component 1 (mARC1), which catalyses the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles , This protein comprises two structural domains which consist of non successive secondary-structure element, with mainly β-strands forming three- and four-stranded antiparallel β-sheets and several α-helices of different lengths .

This domain, also known as the MOSC_N domain, is often found to the N terminus of MOSC domain (

).
Ribosomal biogenesis, methyltransferase, EMG1/NEP1 (Rbsml_bgen_MeTrfase_EMG1/NEP1)
Type: Family

8S rRNA (pseudouridine(1248)-N1)-methyltransferase Nep1 (also known as EMG1) methylates pseudouridine at position1248 (Psi1248) in 18S rRNA and is required for small subunit (SSU) ribosomal RNA (rRNA) maturation . Mutations in the human homologue cause Bowen-Conradi Syndrome . Nep1 is a member of the SPOUT (SpoU-TrmD) methyltransferase (MTase) superfamily, a large class of S-adenosyl-L-methionine (AdoMet or SAM)-dependent RNA MTases which are structurally characterised by a deep trefoil knot .
Nepovirus coat protein, C-terminal (Nepo_coat_C)
Type: Domain

Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection .

This domain aligns several nepovirus coat protein sequences. In several cases, this is found at the C terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped β-barrel domains, and forms a pseudo T = 3 icosahedral capsid structure .
Nepovirus coat protein, N-terminal (Nepo_coat_N)
Type: Domain

Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection .

This family includes several nepovirus coat protein sequences. In several cases, this is found at the C terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped β-barrel domains, and forms a pseudo T = 3 icosahedral capsid structure .