SII-SWORD/CoKE huggingface dataset:
Acetylcholinesterase, tetramerisation domain (AChE_tetra)
Type: Domain

Cholinesterase enzymes are members of the broader alpha/beta hydrolase family and can be dividied into two distinct groups: those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases

)

acetylcholine + H
2
O ->choline + acetate

and those that catalyse the conversion of other acylcholines to a choline and a weak acid (cholinesterases

)

an acylcholine + H
2
O ->choline + a carboxylate

Acetylcholinesterase also acts on a variety of acetic esters and catalyses transacetylations. It is the most intensively studied of the cholinesterase enzymes due to its key physiological role in the turnover of the neurotransmitter acylcholine . This enzyme is found in, or attached to, cellular or basement membranes of presynaptic cholinergic neurons and postsynaptic cholinoceptive cells within the neuromuscular junction. Signal transmission at the neuromuscular junction involves the release of acylcholine, its interaction with the acycholine receptor and hydrolysis, all occuring in a period of a few milliseconds. Rapid hydrolysis of the newly released aceytlcholine is vital in order to prevent continuous firing of the nerve impulses . Consistent with its role in this process, acetylcholinesterase has an unusually high turnover number, ensuring that acetylcholine is broken down quickly. There is evidence to suggest that acetylcholinesterase has additional important roles including involvement in neuronal adhesion, the formation of Alzheimer fibrils, and neurite growth .

The acetylcholinesterase tetramerisation domain is found at the C terminus and forms a left handed superhelix.
Poly(A)-specific ribonuclease, RNA-binding (PolyA-riboNase_RNA-binding)
Type: Domain

This domain corresponds to the RNA binding domain of Poly(A)-specific ribonuclease (PARN). PARN is a 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails .
MutL, C-terminal, dimerisation (MutL_C)
Type: Domain

MutL and MutS are key components of the DNA repair machinery that corrects replication errors . MutS recognises mispaired or unpaired bases in a DNA duplex and in the presence of ATP, recruits MutL to form a DNA signalling complex for repair. The N-terminal region of MutL contains the ATPase domain and the C-terminal is involved in dimerisation .
Baseplate structural protein Gp11 (Baseplate_struct_Gp11)
Type: Family

The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres . The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation .
RsbS co-antagonist protein RsbRA N-terminal domain (RsbRA_N)
Type: Domain

The general stress response in Bacillus subtilis is governed by sigma(B), whose activity is controlled by a partner switching mechanism in which key protein interactions are governed by serine phosphorylation. In the environmental stress pathway, the RsbS antagonist binds and inactivates the RsbT switch protein/kinase. Following stress, RsbT phosphorylates RsbS, releasing RsbT to bind and activate the RsbU phosphatase.

RsbRA (also known as RsbR) was previously reported to be a positive regulator that enhances RsbT kinase activity . It has since been reported instead to function as a co-antagonist of RsbS .

For RsbS to function, it requires one of a family of four co-antagonist proteins, named RsbRA (RsbR), RsbRB (YkoB), RsbRC (YojH) and RsbRD (YqhA). These RsbRA paralogs each have a a C-terminal domain closely resembling the entire RsbS protein . The N-terminal domain of RsbRA has been reported to show a classic globin fold. However, structural analysis has not revealed the presence of any bound cofactor, such as heme .
Dissimilatory sulphite reductase D (DsrD)
Type: Domain

The structure of the dissimilatory sulphite reductase D (DsrD) protein has shown it to contain a winged-helix motif similar to those found in DNA binding proteins . The structure suggests a possible role for DsrD in transcription or translation of genes, which catalyse dissimilatory sulphite reduction.
TATA-box binding (DUF1779)
Type: Family

This is a family of bacterial proteins. YwmB from Bacillus subtilis contains a circularly permuted TATA-box binding protein-like fold (PDB 2FPN).
Antitoxin TacA 1-like (TacA_1-like)
Type: Family

This protein family includes Antitoxin TacA 1 from Salmonella typhimurium and similar short sequences mainly found in bacteria. TacA1, the antitoxin component of a type II toxin-antitoxin (TA) system, counteracts the toxic effect of cognate toxin TacT1. TacT1 is active in complex with its antitoxin, acetylation of this antitoxin upregulates the acetylation of tRNAs by TacT1 .
Protein of unknown function DUF1780, putative endonuclease (DUF1780)
Type: Family

This is a family of uncharacterised proteins. The structure of a hypothetical protein from Pseudomonas aeruginosa has shown it to adopt an α/β fold, placing it in the Endonuclease superfamily/clan of restriction endonucleases.
CAMSAP, CKK domain (CKK_CAMSAP)
Type: Domain

The CKK domain occurs at the C-terminal in CAMSAP proteins. The structure of the CKK domain is a β-barrel with an associated α-helical hairpin. Characteristically, the CKK domain has a single invariant tryptophan residue within the core of the predicted β-barrel. Residues that interact with this Trp to form part of this core are highly conserved too.

The calmodulin-regulated spectrin-associated (CAMSAP) proteins are defined by a CKK domain that binds microtubules . It includes CAMSAPs from vertebrates and Patronin from invertebrates . CAMSAP1 is the representative member. It contains a conserved region, CC1, that binds to both spectrin and Ca2+/calmodulin in vitro and links spectrin-binding to neurite outgrowth . Patronin binds to and protects the MT minus-end against depolymerization . CAMSAP2 is a key microtubule-organising protein that specifically binds the minus end of non-centrosomal microtubules and regulates their dynamics and organisation. CAMSAP proteins carry an N-terminal region that includes two CH domains represented by

and

, a central region including a predicted coiled-coil, and a C-terminal CKK domain

, which is involved in binding CAMSAP proteins to microtubules .
Protein Ocr (Ocr)
Type: Family

Protein Ocr protects Bacteriophage T7 DNA from degradation and modification by the host restriction-modification complex . The structure of Ocr from T7 has shown that this protein mimics the size and shape of a bent DNA molecule, that binds to and completely occupies the DNA-binding sites of all known families of the complex type I DNA restriction enzymes which inhibits the restriction endonuclease activity . Ocr binds to bacterial RNA polymerase (RNAP) and competes with sigma factors resulting in host transcription inhibition and it also inhibits the host exclusion defense system BREX .
Mediator complex, subunit Med5, fungi (Mediator_Med5_fun)
Type: Family

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.

This entry represents the Med5 subunit of the Mediator complex in fungi. Deletion of the MED5 gene leads to increased transcription of nuclear genes encoding components of the oxidative phosphorylation machinery, and decreased transcription of mitochondrial genes encoding components of the same machinery .
Golgi to ER traffic protein 2 (GET2)
Type: Family

The Golgi to ER traffic (GET) complex is composed of Get1, Get2 and Get3. The complex is involved in the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum . Get1 and Get2 form a transmembrane complex and interact with Get3, an ATPase which recognises and selectively binds the transmembrane domain of TA proteins in the cytosol .
DNA repair protein Nse5/Nse6 (DNA_repair_Nse5/Nse6)
Type: Family

Nse5 and Nse6 are non-structural nuclear proteins that are critical for chromosome segregation in fission yeast . Nse5 forms a dimer with Nse6 and facilitates DNA repair as part of the Smc5-Smc6 holocomplex. Nse6 is also known as KRE29.
Mitochondrial protein Pet20-like (Pet20-like)
Type: Family

This entry includes a group of fungi mitochondrial proteins, including Pet20, Sue1 and Mrx6 (YNL295W) from budding yeasts. This entry also includes Cox24 from fission yeasts.

Pet20 is a mitochondrial protein which is thought to play a role in the correct assembly/maintenance of mitochondrial components . Sue1 is required for degradation of unstable forms of cytochrome c . Cox24, which is also named Small ribosomal subunit protein mS38, is a mitochondrial protein required for processing of the Cox1 transcript .
SKG6/TOS2-like (SKG6/TOS2-like)
Type: Family

This fungal protein family includes SKG6 and TOS2 from Saccharomyces cerevisiae, which are membrane proteins that show polarised intracellular localisation .
Ubiquitin-fold modifier-conjugating enzyme 1 (Ufc1)
Type: Family

Ubiquitin-like (UBL) post-translational modifiers are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. Ubiquitin-fold modifier 1 (Ufm1) a ubiquitin-like protein is activated by a novel E1-like enzyme, Uba5, by forming a high-energy thioester bond. Activated Ufm1 is then transferred to its cognate E2-like enzyme, Ufc1, in a similar thioester linkage. This family represents the E2-like enzyme which catalyses the second step in ufmylation .
Cytochrome c oxidase assembly factor 1 (Coa1)
Type: Family

Coa1 is an inner mitochondrial membrane protein that associates with Shy1 and is required for cytochrome oxidase complex IV assembly. It contains a conserved hydrophobic segment (amino acids 74-92) with the potential to form a membrane-spanning helix. The N terminus of Coa1 is rich in positively charged amino acids and could form an amphipathic α helix, characteristic of a mitochondrial presequence. A cleavage site for the mitochondrial processing peptidase is predicted adjacent to the presequence. Upon in vitro import into mitochondria, Coa1 is processed to a mature form, indicating that it possesses a cleavable presequence . The eukaryotic cytochrome oxidase complex consists of 12-13 subunits, with three mitochondrial encoded subunits, Cox1-Cox3, forming the core enzyme. Translation of the Cox1 transcript requires the two promoters, Pet309 and Mss51, and the latter has an additional role in translational elongation. Coa1 is necessary for linking the activity of Mss51 to Cox1 insertion into the assembly complex .
DNA replication factor Dna2, N-terminal (DNA_replication_fac_Dna2_N)
Type: Domain

This entry represents N-terminal domain of the DNA replication factor Dna2.

Dna2 and its plant homologue JHS1 are DNA replication factors with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities. It is required for Okazaki fragment processing and is involved in DNA repair pathways . The helicase activity is weak and its function remains unclear .
Fcf2 pre-rRNA processing, C-terminal (Fcf2_C)
Type: Domain

This domain is found in eukaryotic nucleolar proteins that are involved in pre-rRNA processing .
Argonaute, linker 1 domain (ArgoL1)
Type: Domain

ArgoL1 is a region found in argonaute proteins. It normally co-occurs with BAG domain (

) and Piwi domain (

). It is a linker region between the N-terminal and the PAZ domains. It contains an α-helix packed against a three-stranded antiparallel β-sheet with two long β-strands (β8 and β9) of the sheet spanning one face of the adjacent N and PAZ domains. L1 together with linker 2, L2, PAZ and ArgoN forms a compact global fold .
Vacuolar protein sorting-associated protein 51 (Vps51)
Type: Family

The VFT tethering complex (also known as GARP complex, Golgi associated retrograde protein complex, Vps53 tethering complex) is a conserved eukaryotic docking complex which is involved in recycling of proteins from endosomes to the late Golgi. Vps51 (also known as Ang2 or Vps67) is a subunit of VFT and interacts with the SNARE Tlg1 . It is also part of the endosome-associated recycling protein (EARP) complex which is structurally related to GARP complex .
Guanine nucleotide-binding protein-like 3, N-terminal domain (Gnl3_N_dom)
Type: Domain

This entry represents an N-terminal domain found in Guanine nucleotide-binding protein-like 3 , Nuclear GTP-binding protein NUG1 , GTPase Grn1 and other related proteins. The function of this domain is unknown.
Phospholipase C-beta, C-terminal domain (PLC-beta_C)
Type: Domain

This domain corresponds to the α helical C-terminal domain of phospholipase C beta (also known a 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta) .
tRNA (1-methyladenosine) methyltransferase catalytic subunit Gcd14 (tRNA_MeTrfase_Gcd14)
Type: Family

Gcd14, also known as Trm61, is the catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase , which is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA .
Gag protein p6 (Gag_p6)
Type: Domain

HIV protein p6 contains two late-budding domains (L domains) which are short sequence motifs essential for viral particle release. p6 interacts with the endosomal sorting complex and represents a docking site for several cellular and binding factors . The PTAP motif interacts with the cellular budding factor TSG101 . This domain is also found in some chimpanzee immunodeficiency virus (SIV-cpz) proteins.
Bacteriophage/plasmid primase, P4, C-terminal (Phage/plasmid_primase_P4_C)
Type: Domain

This domain is found in D5 proteins of DNA viruses, also known as Uncoating factor OPG117, and bacteriophage P4 DNA primase.
Primase, C-terminal 2 (PriCT_2)
Type: Domain

This α helical domain is found at the C-terminal of primases.
Primase, C-terminal 1 (PriCT_1)
Type: Domain

This α helical domain is found at the C-terminal of primases.
Inositol 1,4,5-trisphosphate/ryanodine receptor (Ins145_P3_rcpt)
Type: Domain

This domain corresponds to the ligand binding region on inositol 1,4,5-trisphosphate receptor, and the N-terminal region of the ryanodine receptor. Both receptors are involved in Ca2+ release. They can couple to the activation of neurotransmitter-gated receptors and voltage-gated Ca2+ channels on the plasma membrane, thus allowing the endoplasmic reticulum to discriminate between different types of neuronal activity .
Non-structural protein NSP9, coronavirus (NSP9_CoV)
Type: Domain

NSP9 is a single-stranded RNA-binding viral protein involved in RNA synthesis, essential for the coronavirus replication . The dimerisation of NSP9 is essential for binding and orienting RNA for subsequent use by the replicase machinery. NSP9 is composed of seven antiparallel β-strands and a single α-helix hat are arranged into a single compact domain and form a cone-shaped β-barrel flanked by the C-terminal α-helix (

) . The NSP9 dimer interface is formed by the N-finger motifs and the parallel association of the C-terminal α-helices GXXXG motifs. The N- and C-terminal regions are more conserved than the central core one, and the GXXXG motif is strictly conserved . NSP9 binds to discrete regions on the 7SL RNA component of the signal recognition particle (SRP) and interfere with protein trafficking to the cell membrane upon infection, which interferes with essential host functions, and suppresses host immune defenses .
Scaffold protein Nfu/NifU, N-terminal (Nfu/NifU_N)
Type: Domain

Iron-sulphur (FeS) clusters are important cofactors for numerous proteins involved in electron transfer, in redox and non-redox catalysis, in gene regulation, and as sensors of oxygen and iron. These functions depend on the various FeS cluster prosthetic groups, the most common being [2Fe-2S] and [4Fe-4S] . FeS cluster assembly is a complex process involving the mobilisation of Fe and S atoms from storage sources, their assembly into [Fe-S] form, their transport to specific cellular locations, and their transfer to recipient apoproteins. So far, three FeS assembly machineries have been identified, which are capable of synthesising all types of [Fe-S] clusters: ISC (iron-sulphur cluster), SUF (sulphur assimilation), and NIF (nitrogen fixation) systems.

In the NIF system, NifS and NifU are required for the formation of metalloclusters of nitrogenase in Azotobacter vinelandii, and other organisms, as well as in the maturation of other FeS proteins. Nitrogenase catalyses the fixation of nitrogen. It contains a complex cluster, the FeMo cofactor, which contains molybdenum, Fe and S. NifS is a cysteine desulphurase. NifU binds one Fe atom at its N-terminal, assembling an FeS cluster that is transferred to nitrogenase apoproteins . Nif proteins involved in the formation of FeS clusters can also be found in organisms that do not fix nitrogen .

This domain is found at the N terminus of NifU (from NIF system) and NifU related proteins, and in the human Nfu protein. Both of these proteins are thought to be involved in the assembly of iron-sulphur clusters, functioning as scaffolds .
DNA alkylation repair enzyme (DNA_alkylation)
Type: Family

These proteins are predicted to be DNA alkylation repair enzymes. The structure of a hypothetical protein shows it to adopt a super coiled α helical structure.
Formaldehyde-activating enzyme (HCHO-activating_enzyme)
Type: Domain

This family consists of formaldehyde-activating enzyme, or the corresponding domain of longer, bifunctional proteins. It links formaldehyde to the C1 carrier tetrahydromethanopterin (H4MPT), an analog of tetrahydrofolate, and is common among species with H4MPT . The ribulose monophosphate (RuMP) pathway, which removes the toxic metabolite formaldehyde by assimilation, runs in the opposite direction in some species to produce ribulose 5-phosphate for nucleotide biosynthesis, leaving formaldehyde as an additional metabolite. In these species, formaldehyde activating enzyme may occur as a fusion protein with D-arabino 3-hexulose 6-phosphate formaldehyde lyase from the RuMP pathway.
Non-structural protein NSP7, coronavirus (NSP7_CoV)
Type: Domain

Non-structural protein NSP7 has been implicated in viral RNA replication and is predominantly α-helical in structure. Its central core is an N-terminal helical bundle (HB), with helices HB1, HB2 and HB3, forming a triple-stranded antiparallel coiled coil with a right-handed superhelical pitch. It is part of the RNA-dependent RNA polymerase (RdRp) heterotetramer which consists of one NSP7, two NSP8 molecules and the catalytic NSP12, defined as the minimal core component for mediating coronavirus RNA synthesis . NSP7 and NSP8 forms a complex that adopts a hollow cylinder-like structure . The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase . NSP7 and NSP8 play a role in the stabilisation of NSP12 regions involved in RNA binding, and are essential for a highly active NSP12 polymerase complex .
Non-structural protein NSP8, coronavirus (NSP8_CoV)
Type: Domain

Viral non-structural protein NSP8 is part of the RNA-dependent RNA polymerase (RdRp) complex and forms a heterotetramer consisting of one molecule of NSP7, two copies of NSP8 and one of NSP12 . NSP8 and NSP7 adopts a hollow cylinder-like structure in which the dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RdRp . NSP7 and NSP8 are co-factors for the catalytic NSP12 that play a role in the stabilisation of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex . It has been demonstrated that NSP8 from human coronavirus 229E acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities . NSP8 has N-terminal and C-terminal D/ExD/E conserved motifs. The N-terminal motif is critical for RNA polymerase activity as these residues are part of the Mg2-binding active site .
NSP8 has a 'golf club'-like structure composed of a long α-helix N-terminal 'shaft' subdomain and an α/β C-terminal 'head' subdomain consisting of three α-helices and seven β-strands (

). The seven β-strands form an open-barrel with two antiparallel β-sheets packed orthogonally. More than half the residues in the C-terminal domain are hydrophobic, and the whole domain forms a tight hydrophobic core .

Together with NSP9, NSP8 suppresses protein integration into the cell membrane, thus, disrupting host immune defenses .
Glycolipid transfer protein domain (Glycolipid_transfer_prot_dom)
Type: Domain

Glycolipid transfer protein (GLTP) is a cytosolic protein that catalyses the intermembrane transfer of glycolipids such as glycosphingolipids, glyceroglycolipids, and possibly glucosylceramides, but not of phospholipids. The GLTP protein consists of a single domain with a multi-helical structure consisting of two layers of orthogonally packed helices .