SII-SWORD/CoKE huggingface dataset:
Class VI myosin, motor domain (MYSc_Myo6)
Type: Domain

Myosin VI is a monomeric myosin, which moves towards the minus-end of actin filaments, in contrast to most other myosins which moves towards the plus-end of actin filaments. It is thought that myosin VI, unlike plus-end directed myosins, does not use a pure lever arm mechanism, but instead steps with a mechanism analogous to the kinesin neck-linker uncoupling model . Myosin VI mediates cargo transport and also serves as an anchor that supports cellular architectures by physically connecting cytoskeletons with its binding targets, such as membranes. It has being implicated in a myriad of functions: the transport of cytoplasmic organelles, maintenance of normal Golgi morphology, endocytosis, secretion, cell migration, border cell migration during development, and in cancer metastasis, playing roles in deafness and retinal development among others . While how this is accomplished is largely unknown there are several interacting proteins that have been identified such as disabled homologue 2 (DAB2), GIPC1, synapse-associated protein 97 (SAP97; also known as DLG1) and optineurin, which have been found to target myosin VI to different cellular compartments .
GCM domain superfamily (GCM_dom_sf)
Type: Homologous_superfamily

GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been identified in proteins belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian homologues . In GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 residues. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved.

The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' . The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues . The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding . The GCM domain is a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain . The GCM domain consists of a large and a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five-and three-stranded β-sheets, respectively, with three small helical segments packed against the same side of the two β-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded β-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the β-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.
Fibronectin type III superfamily (FN3_sf)
Type: Homologous_superfamily

Fibronectin is a dimeric glycoprotein composed of disulfide-linked subunits
with a molecular weight of 220-250kDa each. It is involved in cell adhesion,
cell morphology, thrombosis, cell migration, and embryonic differentiation. Fibronectin is a modular protein composed of homologous repeats of three
prototypical types of domains known as types I, II, and III .

Fibronectin type-III (FN3) repeats are both the largest and the most common of the fibronectin subdomains. Domains homologous to FN3 repeats have been found
in various animal protein families including other extracellular-matrix
molecules, cell-surface receptors, enzymes, and muscle proteins . Structures of individual FN3 domains have revealed a conserved β-sandwich fold with one β-sheet containing four strands and the other sheet containing three strands (see for example

) . This fold is topologically very similar to that of Ig-like domains, with a notable difference being the lack of a conserved disulfide bond in FN3 domains. Distinctive hydrophobic core packing and the lack of detectable
sequence homology between immunoglobulin and FN3 domains suggest, however,
that these domains are not evolutionarily related .

FN3 exhibits functional as well as structural modularity. Sites of interaction with other molecules have been mapped to short stretch of amino acids such as the Arg-Gly-Asp (RGD) sequence found in various FN3 domains. The RGD sequences is involved in interactions with integrin. Small peptides containing the RGD sequence can modulate a variety of cell adhesion invents associated with thrombosis, inflammation, and tumour metastasis. These properties have led to the investigation of RGD peptides and RGD peptide analogues as potential therapeutic agents .
DhaL domain superfamily (DhaL_dom_sf)
Type: Homologous_superfamily

Dihydroxyacetone (Dha) kinases are a family of sequence-conserved enzymes that phosphorylate dihydroxyacetone, glyceraldehyde and other short-chain ketoses and aldoses. They can be divided into two groups according to the source of high-energy phosphate that they utilise, either ATP or phosphoenolpyruvate (PEP). The ATP-dependent forms are the two-domain Dha kinases (DAK), which occur in animals, plants and eubacteria. They consist of a Dha binding (K) and an ATP binding (L) domain. The PEP-dependent forms occur only in eubacteria and a few archaebacteria and consist of three subunits. Two subunits, DhaK and DhaL, are homologous to the K and L domains. Intriguingly, the ADP moiety is not exchanged for ATP but remains permanently bound to the DhaL subunit where it is rephosphorylated in situ by the third subunit, DhaM, which is homologous to the IIA domain of the mannose transporter of the bacterial PEP:sugar phosphotransferase system (PTS) .

The DhaL domain consists of eight antiparallel α-helices arranged in an up-and-down geometry and aligned on a circle. This results in the formation of a helix barrel enclosing a deep pocket. The helices are amphipathic with the hydrophobic side chains directed into the pocket of the barrel and with the polar residues exposed. The nucleotide is bound on the top of the barrel .

The DhaL α helix barrel fold appears not only as a C-terminal domain in Dha kinases but also as an N-terminal domain in a family of two-domain proteins with unknown function. One representative example is YfhG of Lactococcus lactis .
UreE urease accessory, N-terminal domain superfamily (UreE_N_sf)
Type: Homologous_superfamily

Urease and other nickel metalloenzymes are synthesised as precursors devoid of the metalloenzyme active site. These precursors then undergo a complex post-translational maturation process that requires a number of accessory proteins.

Members of this group are nickel-binding proteins required for urease metallocentre assembly . They are believed to function as metallochaperones to deliver nickel to urease apoprotein . It has been shown by yeast two-hybrid analysis that UreE forms a dimeric complex with UreG in Helicobacter pylori . The UreDFG-apoenzyme complex has also been shown to exist and is believed to be, with the addition of UreE, the assembly system for active urease . The complexes, rather than the individual proteins, presumably bind to UreB via UreE/H recognition sites.

The structure of Klebsiella aerogenes UreE reveals a unique two-domain architecture.The N-terminal domain is structurally related to a heat shock protein, while the C-terminal domain shows homology to the Atx1 copper metallochaperone . Significantly, the metal-binding sites in UreE and Atx1 are distinct in location and types of residues despite the relationship between these proteins and the mechanism for UreE activation of urease is proposed to be different from the thiol ligand exchange mechanism used by the copper metallochaperones.

The N-terminal domain is termed the peptide-binding domain. Deletion of this domain does not eliminate enzymatic activity, and the truncated protein can still activate urease . It has a closed barrel fold and a crossover loop topology.
Nitric oxide synthase, N-terminal domain superfamily (NOS_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of the nitric oxide synthases.
Staphylokinase/Streptokinase superfamily (SAK/SK_sf)
Type: Homologous_superfamily

This entry represents staphylokinases and streptokinases.

Staphylokinase (also known as SAK) from Staphylococcus aureus is a virulence factor due to its interaction with plasminogen and alpha-defensins in the hosts. The binding of staphylokinase to plasminogen results in the formation of active plasmin, a proteolytic enzyme facilitating bacterial penetration into the surrounding tissues . However, once the host tissues are infected, the interaction between staphylokinase and plasminogen decreases disease severity . The three-dimensional structure of streptokinase is believed to contain two independently folded domains, each with a ubiquitin-like fold.

Streptokinase (SK) can be found in several species of Streptococci. It can bind not only plasminogen, but also host fibrinogen . This close interaction with the human fibrinolytic system allows the microbe to acquire unregulatable cell-surface enzymatic activity, promoting further spread from the site of infection. The complexes formed between streptococcal cells, streptokinase, plasminogen and fibrinogen can lyse fibrin clots in the host . Streptokinase has been used to treat acute myocardial infarction .

Staphylokinases and streptokinases have a β(2)-α-β(2) fold with a mixed β-sheet topology.
ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain superfamily (ATPase_F1/V1/A1_a/bsu_N_sf)
Type: Homologous_superfamily

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 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.

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.
SK, calmodulin-binding domain superfamily (CaM-bd_dom_sf)
Type: Homologous_superfamily

Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM) . CaM binds to the SK channel through this the CaM-binding domain (CaMBD), which is located in an intracellular region of the alpha-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of
CaM. The structure of this domain complexed with CaM is known . This domain forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three α-helices, two from one CaMBD subunit and one from the other.
Methane monooxygenase, gamma chain superfamily (Me_mOase_sf_g)
Type: Homologous_superfamily

Methane monooxygenases (

) catalyse the oxidation of methane to methanol in the presence of oxygen and NADH in methanotrophs. It has a broad specificity, hydroxylating many alkanes, and converting alkenes into the corresponding epoxides. In additional reactions, CO is oxidized to CO2, ammonia is oxidized to hydroxylamine, and some aromatic compounds and cyclic alkanes can also be hydroxylated, although more slowly. In Methylococcus capsulatus there are two forms of the enzyme, a soluble and a membrane-bound type. The soluble form consists of 3 components, A, B and C. Protein A is made up of 3 chains, alpha, beta and gamma.

This entry represents the gamma chain of methane monooxygenases. Structurally, the gamma chain contains two domains, each consisting of a three helices arranged in an open bundle topology .
Class X myosin, motor domain (MYSc_Myo10)
Type: Domain

Myosin X is an unconventional myosin found to localize to filopodia. It is thought to be involved in numerous processes ranging from invadopodia formation to cell migration . Myosin X walks towards the barbed ends of filaments and is thought to walk both on bundles of actin and single filaments, a unique behaviour . The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. C-terminal to the head domain are a variable number of IQ domains, 2 PH domains, a MyTH4 domain, and a FERM domain.
Class XXI myosin, motor domain (MYSc_Myo21)
Type: Domain

Myosins are present in all eukaryotes including protozoan parasites . Myosins are characterised by three domains: an N-terminal motor or head domain that binds ATP and filamentous actin, a neck domain which binds light chains or calmodulin, and a C-terminal tail which is highly divergent . Class XXI myosins are found in trypanosomatids. They are preferentially localised in the proximal region of the flagellum; this localisation is determined by the myosin tail .

This entry represents the motor or head domain of class XXI myosins.
Tubulin binding cofactor A superfamily (TBCA_sf)
Type: Homologous_superfamily

The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP .

This entry represents tubulin binding cofactor A (TBCA) from animal, plants and fungi. Human TBCA functions as a molecular chaperone for beta-tubulin . Budding yeast TBCA, also known as Rbl2, may bind transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic . The sequence identity of Rbl2 and human TBCA is only 32%, they appear to be structurally distinct and may interact with beta-tubulin by different mechanisms .

The structure of TBCA has three helices forming a bundle closed fold with left-handed twist topology going up-and-down.
CcmE-like superfamily (CcmE-like_sf)
Type: Homologous_superfamily

CcmE is the product of a cluster of Ccm genes that are necessary for cytochrome c biosynthesis in many prokaryotes and plant mitochondria . In E. coli, expression of these proteins is induced when the organisms are grown under anaerobic conditions with nitrate or nitrite as the final electron acceptor .

The CcmE structure presents a close or partly open barrel fold and a greek-key topology.
Plus3-like superfamily (Plus3-like_sf)
Type: Homologous_superfamily

The yeast Paf1 complex consists of Pfa1, Rtf1, Cdc73, Ctr9, and Leo1. The complex regulates histone H2B ubiquitination, histone H3 methylation, RNA polymerase II carboxy-terminal domain (CTD) Ser2 phosphorylation, and RNA 3' end processing. The conservation of Paf1 complex function in higher eukaryotes has been confirmed in human cells, Drosophila and Arabidopsis. The Plus3 domain spans the most conserved regions of the Rtf1 protein and is surrounded by regions of low complexity and coiled-coil propensity . It contains only a limited number of highly conserved amino acids, among which are three positively charged residues that gave the Plus3 domain its name. The capacity to bind single-stranded DNA is at least one function of the Plus3 domain .

The plus-3 domain is about 90 residues in length and is often found associated with the GYF domain (

). The Plus3 domain structure consists of six α-helices intervened by a sequence of six β-strands in a mixed α/β topology. β-strands 1, 2, 5, and 6 compose a four-stranded antiparallel β-sheet with a β-hairpin insertion formed by strands 3 and 4. The N-terminal helices α1-α3 and C-terminal helix α6 pack together to form an α subdomain, while the β-strands and the small 3(10) helix α4 form a β-subdomain. The two subdomains pack together to form a compact, globular protein .
Glycerate kinase superfamily (Glycerate_kinase_sf)
Type: Homologous_superfamily

This superfamily includes glycerate kinase 2 (

), which catalyses the phosphorylation of (R)-glycerate to 3-phospho-(R)-glycerate in the presence of ATP. There are two glycerate kinases in E. coli, known as GKI and GKII and GKII is encoded by glxK .

The structure of the glycerate kinase consists of two different α/β domains. The first domain has a Flavodoxin-like fold (

): three layers (α/β/α) with parallel β-sheet of five strand. The second domain is similar to the Restriction endonuclease-like fold (

): three layers (α/β/α) with mixed β-sheet of five strands, and is inserted into the first one.
Pyridoxine 5'-phosphate synthase (Pyridoxine-5'_phos_synth)
Type: Homologous_superfamily

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .

In Escherichia coli, the pdx genes involved in vitamin B6 have been characterised . This entry represents PdxJ (also called PNP synthase), which catalyses the condensation of 4-hydroxy-L-threonine and 1-deoxy-D-xylulose-5-phosphate to form pyridoxine-5'-phosphate (PNP) . The product of the PdxJ reaction is then oxidized by PdxH to form pyridoxal 5'-phosphate (PLP).

PNP synthase (PdxJ) adopts a TIM barrel topology. Intersubunit contacts are mediated by three ''extra'' helices, generating a tetramer of symmetric dimers with shared active sites. The open state has been proposed to accept substrates and to release products, while most of the catalytic events are likely to occur in the closed state. A hydrophilic channel running through the centre of the barrel was identified as the essential structural feature that enables PNP synthase to release water molecules produced during the reaction from the closed, solvent-shielded active site .
Tombusvirus P19 superfamily (VP19_sf)
Type: Homologous_superfamily

This entry represents the Tombusvirus P19 (VP19) core domain superfamily. VP19 has a β(2)-α-β(2)-α fold with two layers (α/β) and antiparallel sheet topology.
Vacuolar ATP synthase subunit C superfamily (Vac_ATP_synth_c_sf)
Type: Homologous_superfamily

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.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents the C subunit that is part of the V1 complex, and is localised to the interface between the V1 and V0 complexes . This subunit does not show any homology with F-ATPase subunits. The C subunit plays an essential role in controlling the assembly of V-ATPase, acting as a flexible stator that holds together the catalytic (V1) and membrane (V0) sectors of the enzyme . The release of subunit C from the ATPase complex results in the dissociation of the V1 and V0 subcomplexes, which is an important mechanism in controlling V-ATPase activity in cells.

The vacuolar ATP synthase subunit C structure has two α+β (sub)domains, each has a ferredoxin-like fold (

), connected with 3-helical bundle.