SII-SWORD/CoKE huggingface dataset:
4-vinyl reductase, 4VR (V4R)
Type: Domain

Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small molecules by specialised domains. The 4-vinyl reductase (4VR) domain is a predicted small molecular binding domain, that may bind to hydrocarbons . Proteins that contain this domain include a regulator of the phenol catabolic pathway and a protein involved in chlorophyll biosynthesis.
DHHA2 domain (DHHA2)
Type: Domain

This domain is called DHHA2 since it is often associated with the DHH domain (

) and is diagnostic of DHH subfamily 2 members . The domain is about 120 residues long and contains a conserved DXK motif at its amino terminus. It is present in inorganic pyrophosphatases and in exopolyphosphatase of Saccharomyces cerevisiae.
Prp18 (Prp18)
Type: Domain

The splicing factor Prp18 is required for the second step of pre-mRNA splicing. PRP18 appears to be primarily associated with the U5 snRNP.

The structure of a large fragment of the Saccharomyces cerevisiae Prp18 is known . This fragment is fully active in yeast splicing
in vitro
and includes the sequences of Prp18 that have been evolutionarily conserved. The core structure consists of five α-helices that adopt a novel fold. The most highly conserved region of Prp18, a nearly invariant stretch of 19 aa, forms part of a loop between two α-helices and may interact with the U5 small nuclear ribonucleoprotein particles .
Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain (Pyr_nucl-diS_OxRdtase_dimer)
Type: Domain

This entry represents a dimerisation domain that is usually found at the C-terminal of both class I and class II oxidoreductases, as well as in NADH oxidases and peroxidases .
ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain (ATPase_F1/V1/A1_a/bsu_N)
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 . This entry represents the N-terminal domain, which forms a closed β-barrel with Greek-key topology.
Mur ligase, C-terminal (Mur_ligase_C)
Type: Domain

This entry represents the C-terminal domain from all four stage 2 Mur enzymes: UDP-N-acetylmuramate-L-alanine ligase (MurC), UDP-N-acetylmuramoylalanine-D-glutamate ligase (MurD), UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase (MurE), and UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF). This entry also includes the C-terminal domain of folylpolyglutamate synthase that transfers glutamate to folylpolyglutamate and cyanophycin synthetase that catalyses the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin) .

The C-terminal domain is almost always associated with the cytoplasmic peptidoglycan synthetases, N-terminal domain (see

).

The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:

(1) formation of UDP-N-acetylmuramic acid (UDPMurNAc) from N-acetylglucosamine (GlcNAc).

(2) addition of a short polypeptide chain to the UDPMurNAc.

(3) addition of a second GlcNAc to the disaccharide-pentapeptide building block and transport of this unit through the cytoplasmic membrane and incorporation into the growing peptidoglycan layer.

Stage two involves four key Mur ligase enzymes: MurC (

) , MurD (

) , MurE (

) and MurF (

) . These four Mur ligases are responsible for the successive additions of L-alanine, D-glutamate, meso-diaminopimelate or L-lysine, and D-alanyl-D-alanine to UDP-N-acetylmuramic acid . All four Mur ligases are topologically similar to one another, even though they display low sequence identity. They are each composed of three domains: an N-terminal Rossmann-fold domain responsible for binding the UDPMurNAc substrate; a central domain (similar to ATP-binding domains of several ATPases and GTPases); and a C-terminal domain (similar to dihydrofolate reductase fold) that binds the incoming amino acid . Residues found in the three domains (the Asp50, Lys130 (GKT motif), and Glu174 residues, MurC numbering) are involved in the catalytic process . The conserved sequence motifs found in the four Mur enzymes also map to other members of the Mur ligase family, including folylpolyglutamate synthetase, cyanophycin synthetase and the capB enzyme from Bacillales .
Poly(ADP-ribose) polymerase, regulatory domain (Poly(ADP-ribose)pol_reg_dom)
Type: Domain

Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The regulatory domain of the polymerase is almost always associated with the C-terminal catalytic domain (see

).

This domain consists of a duplication of two helix-loop-helix structural repeats .
Polysaccharide lyase family 8, C-terminal (Lyase_8_C)
Type: Domain

Proteins containing this domain consist of a group of secreted bacterial lyase enzymes capable of acting on hyaluronan (hyaluronate lyase,

) and chondroitin (chondroitin AC lyase,

) in the extracellular matrix of host tissues, contributing to the invasive capacity of the pathogen . This domain is almost always associated with the polysaccharide lyase family 8, N-terminal domain (see

). This entry represents the C-terminal domain of hyaluronate and chondroitin AC lyase enzymes.
Gfo/Idh/MocA-like oxidoreductase, C-terminal (Gfo/Idh/MocA-like_OxRdtase_C)
Type: Domain

This entry represents a domain found C-terminal in Gfo/Idh/MocA family of proteins.

In general, the Gfo/Idh/MocA protein family members are enzymes that catalyse various different chemical reactions such as oxidation and reduction of carbohydrates, oxidation of trans-dihydrodiols, reduction of biliverdin, and hydrolysation of glycosidic bonds. All the enzymes in this family utilise NAD(P) as a hydride donor or acceptor. However, despite the structural similarities, some member such as the transcriptional repressor Gal80p, does not have enzymatic activity .
Histidine kinase CheA-like, homodimeric domain (CheA-like_dim)
Type: Domain

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

This helical bundle domain is the homodimer interface of signal transducing histidine kinases like CheA .
Integrase, SAM-like, N-terminal (Integrase_SAM-like_N)
Type: Domain

Proteins containing this domain cleave DNA substrates by a series of staggered cuts, during which the protein becomes covalently linked to the DNA through a catalytic tyrosine residue at the carboxy end of the alignment .

The phage integrase N-terminal SAM-like domain is almost always found with the signature that defines the phage integrase family (see

).
Iron hydrogenase, large subunit, C-terminal (Fe_hydrogenase_lsu_C)
Type: Domain

Proteins containing this domain may be involved in the mechanism of biological hydrogen activation and contain 4FE-4S clusters. They can use molecular hydrogen for the reduction of a variety of substances. This domain consists of two intertwined α/β subdomains with FE-S cluster located at the interface between these subdomains .
Tetracycline repressor TetR, C-terminal (Repressor_TetR_C)
Type: Domain

This entry represents the C-terminal domain found in the tetracycline transcriptional repressor TetR, which binds to the Tet(A) gene to repress its expression in the absence of tetracycline . Tet(A) is a membrane-associated efflux protein that exports tetracycline from the cell before it can attach to ribosomes and inhibit polypeptide chain growth. TetR occurs as a homodimer and uses two helix-turn-helix (HTH) motifs to bind tandem DNA operators, thereby blocking the expression of the associated genes, TetA and TetR. The structure of the class D TetR repressor protein involves 10 α-helices, with connecting turns and loops. The three N-terminal helices constitute the DNA-binding HTH domain, which has an inverse orientation compared with HTH motifs in other DNA-binding proteins. The core of the protein, formed by helices 5-10, is responsible for dimerisation and contains, for each monomer, a binding pocket that accommodates tetracycline in the presence of a divalent cation.
FAD-binding oxidoreductase/transferase, type 4, C-terminal (FAD-bd_oxidored_4_C)
Type: Domain

This entry represents a domain found in a group of type 4 FAD-binding oxidoreductase/transferases and similar proteins from all cellular organisms, including D-2-hydroxyglutarate dehydrogenase from humans and Escherichia coli , Alkyldihydroxyacetonephosphate synthase from Caenorhabditis elegans and D-2-hydroxyglutarate--pyruvate transhydrogenase DLD2 from Saccharomyces cerevisiae . This domain, often found at the C-terminal end of the proteins, shows a ferredoxin-like fold .
THUMP domain (THUMP_dom)
Type: Domain

The THUMP domain (named after THioUridine synthases, RNA Methylases and Pseudouridine synthases) is a module of approximately 110 amino acid residues involved in RNA metabolism. It is found in enzymes responsible for various RNA modifications, including methylation, pseudouridylation, thiouridylation, deamination, and acetylation. The THUMP domain can occur independently or in association with different catalytic domains, such as methylase, pseudo U-synthase, or PP-loop domains .

The THUMP domain can occur in stand-alone form or in association with a variety of catalytic domains, like methylase, pseudo U-synthase or rhodanese. THUMP is an ancient domain that apparently evolved prior to the divergence of the primary divisions of life. It was initially predicted to have RNA-binding capacity but it was shown later that it associates with the adjacent FLD domain (IPR000241) to display the RNA-binding ability, leading to the delivery of a variety of RNA modification enzymes to their targets. The domain adopts an α/β fold, with two helices packed against a β-sheet .

Recent structural and biochemical studies have established that the THUMP domain plays a crucial role in capturing the 3'-end of RNA substrates, particularly the CCA-terminus of tRNAs. This function is essential for the proper positioning of the RNA substrate for modification by the associated catalytic domains .

THUMP-containing proteins have been identified in all domains of life, including bacteria, archaea, and eukaryotes, indicating their ancient evolutionary origin. Recent studies have also revealed that some THUMP-related proteins are involved in modifications of other RNA types beyond tRNA, such as rRNA .

Some proteins known to contain a THUMP domain are listed below:

Bacterial and archaeal thiI-like 4-thiouridine synthases (also known as tRNA sulfurtransferases).

Bacterial, archaeal and eukaryotic RNA methyltransferases including tRNA methyltransferases.

tRNA pseudouridine synthase Pus10.

tRNA acetyltransferases.

THUMP domain-containing protein.
GAD-like domain superfamily (GAD-like_sf)
Type: Homologous_superfamily

This superfamily represents a 2 layer α/β insertion domain found in the glutamyl-tRNA amidotransferase subunit E and some aspartyl tRNA ligases , and in hypothetical protein PH0730 (

).
Amelogenin (Amelogenin)
Type: Family

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth. They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins .

Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units : the N-terminal region appears to contain β-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive β-turn segment and a "β-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region . The β-spiral offers a probable site for interactions with Ca2+ ions.

Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide .
Olfactory receptor, insect (7tm6_olfct_rcpt)
Type: Family

This entry represents Odorant receptors and Odorant receptor coreceptors that are found mainly insects. The odorant receptor repertoire encodes a large collection of odor stimuli that vary widely in identity, intensity, and duration . The atypical heteromeric and topological design of the odorant receptors appears to be an insect-specific solution for odor recognition. Odor-evoked odorant receptor currents are independent of known G-protein-coupled second messenger pathways.

Odorant coreceptors form complexes with conventional odorant receptors resulting in odorant-sensing units and providing sensitive and prolonged odorant signaling and calcium permeability. Odorant coreceptors are a universal and integral part of the functional odorant receptor, involved in the dendritic localization of other olfactory receptors .

All known members of this group are seven-transmembrane proteins that are candidate odorant receptors in Drosophila.
Hepatitis TT virus, Orf2/Gyrovirus Vp2, N-terminal domain (HEV_TT_vir_Orf2/Gyrovir_Vp2_N)
Type: Domain

This entry represents a domain found in ORF2 from Torque teno virus (TTV) and related viruses. This domain contains a set of conserved cysteine and histidine residues suggesting a zinc binding domain and has been implicated in kinases regulation . TTV, isolated initially from a Japanese patient with hepatitis of unknown aetiology, has since been found to infect both healthy and diseased individuals, and numerous prevalence studies have raised questions about its role in unexplained hepatitis . This domain is also present in the VP2 protein from the chicken anaemia virus which is a gyrovirus. Gyroviruses are small circular single stranded viruses. it is also found in the Protein US1 from Human cytomegalovirus.

Torque teno virus (TTV) is a nonenveloped and single-stranded DNA virus that was initially isolated from a Japanese patient with hepatitis of unknown aetiology, and which has since been found to infect both healthy and diseased individuals . Numerous prevalence studies have raised questions about its role in unexplained hepatitis. ORF2 is a 150 residue protein of unknown function.
Ecdysteroid kinase-like (EcKL)
Type: Family

This family includes ecdysteroid 22-kinase, an enzyme responsible for the phosphorylation of ecdysteroids (insect growth and moulting hormones) at C-22, to form physiologically inactive ecdysteroid 22-phosphates . Most insects contain 12 to 105 genes encoding this family and yet so far only one enzyme (ecdysteroid 22-kinase from Bombyx mori) has characterised substrates (2-deoxyecdysone, ecdysone, 20-hydroxyecdysone). There are good reasons to believe that this family includes kinases that act on other small molecule substrates and that they may function in detoxification processes .
HTLV Tax (Tax)
Type: Family

Human T-lymphotropic virus 1 is the etiological agent for adult T-cell leukemia (ATL), as well as for tropical spastic paraparesis (TSP) and HTLV-I associate myelopathy (HAM). A biological understanding of the involvement of HTLV-I and in ATL has focused significantly on the workings of the virally-encoded 40kDa phospho-oncoprotein, Tax. Tax is a transcriptional activator. Its ability to modulate the expression and function of many cellular genes has been reasoned to be a major contributory mechanism explaining HTLV-I mediated transformation of cells. In activating cellular gene expression, Tax impinges upon several cellular signal-transduction pathways, including those for CREB/ATF and NF-kappaB .
Human herpesvirus K1 glycoprotein, C-terminal (K1_C)
Type: Domain

Current genotyping systems for Human herpesvirus 8 (HHV-8) are based on the highly variable gene encoding the K1 glycoprotein . This entry represents the C-terminal region of the K1 glycoprotein.
Barrier- to-autointegration factor, BAF (BAF_prot)
Type: Family

Barrier-to-autointegration factor (BAF) is an essential protein that is highly conserved in metazoan evolution, and which may act as a DNA-bridging protein . BAF binds directly to double-stranded DNA, to transcription activators, and to inner nuclear membrane proteins, including lamin A filament proteins that anchor nuclear-pore complexes in place, and nuclear LEM-domain proteins that bind to laminins filaments and chromatin. New findings suggest that BAF has structural roles in nuclear assembly and chromatin organisation, represses gene expression and might interlink chromatin structure, nuclear architecture and gene regulation in metazoans .

BAF can be exploited by retroviruses to act as a host component of pre-integration complexes, which promote the integration of the retroviral DNA into the host chromosome by preventing autointegration of retroviral DNA . BAF might contribute to the assembly or activity of retroviral pre-integration complexes through direct binding to the retroviral proteins p55 Gag and matrix, as well as to DNA.
Dim1 family (Dim1)
Type: Family

This entry represents fission yeast Dim1 and its homologues, including Dib1 from budding yeasts, YLS8 from plants and TXNL4 from animals. Dim1 was originally identified as a mitosis protein . Later, it was found to interact with spliceosome component Prp6, which is involved in pre-mRNA splicing . Dim1 may act at the level of mRNA, which impacts the functioning of the APC/C, a critical complex in controlling mitotic progression .

It's worth noting that although the Dim proteins exhibit a thioredoxin-like fold, they lack the disulfide bond required for the thioredoxin redox activity .
Glycoside hydrolase, family 33, N-terminal (Glyco_hydro_33_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.

Sialidases (

) hydrolyse alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates. Sialidases may act as pathogenic factors in microbial infections .

The 1.8 A structure of trans-sialidase from leech (Macrobdella decora,

) in complex with 2-deoxy-2, 3-didehydro-NeuAc was solved. The refined model comprising residues 81-769 has a catalytic β-propeller domain, a N-terminal lectin-like domain and an irregular β-stranded domain inserted into the catalytic domain .
Signal recognition particle, SRP54 subunit, M-domain (Signal_recog_particle_SRP54_M)
Type: Domain

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the M domain of the 54kDa SRP54 component, a GTP-binding protein that interacts with the signal sequence when it emerges from the ribosome. SRP54 of the signal recognition particle has a three-domain structure: an N-terminal helical bundle domain, a GTPase domain, and the M-domain that binds the 7s RNA and also binds the signal sequence. The extreme C-terminal region is glycine-rich and lower in complexity and poorly conserved between species.

This group of proteins include human SRP54 ; Escherichia coli and Bacillus subtilis Ffh protein (Fifty-four homologue), which seems to be the prokaryotic counterpart of SRP54 ; the PilA protein from Neisseria gonorrhoeae, the homologue of FtsY and archaeal SRP54.