SII-SWORD/CoKE huggingface dataset:
Aspartate decarboxylase-like domain superfamily (Asp_de-COase-like_dom_sf)
Type: Homologous_superfamily

β-barrels are commonly observed in protein structures. They are classified in terms of two integral parameters: the number of strands in the sheet, n, and the shear number, S, a measure of the stagger of the strands in the β-sheet. These two parameters have been shown to determine the major geometrical features of β-barrels. Six-stranded β-barrels with a pseudo-twofold axis are found in several proteins. One involving parallel strands forming two psi structures is known as the double-psi barrel. The first psi structure consists of the loop connecting strands β1 and β2 (a 'psi loop') and the strand β5, whereas the second psi structure consists of the loop connecting strands β4 and β5 and the strand β2. All the psi structures in double-psi barrels have a unique handedness, in that β1 (β4), β2 (β5) and the loop following β5 (β2) form a right-handed helix. The unique handedness may be related to the fact that the twisting angle between the parallel pair of strands is always larger than that between the antiparallel pair .

In many cases, including aspartate decarboxylase and aspartic proteinases, strands 1 and 4 are each bent and consist of two sections. The two sections normally make a right angle; sometimes their hydrogen-bond patterns are disrupted at the corner by a bulge or even by a large insertion. In these cases, the barrel can also be viewed as a pair of orthogonally packed sheets, each with four strands.
Mannose-6-phosphate receptor binding domain superfamily (Man6P_isomerase_rcpt-bd_dom_sf)
Type: Homologous_superfamily

Mannose-6-phosphate receptors (MPRs) are transmembrane proteins involved in the transport of lysosomal enzymes from the Golgi complex and the cell surface to lysosomes . Lysosomal enzymes bearing phosphomannosyl residues bind specifically to MPRs in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment, where the low pH mediates dissociation of the complex. There are two distinct MPRs that function in the recognition of mannose-6-phosphate-containing proteins: the cation-dependent MPR (CD-MPR) and the cation-independent MPR (CI-MPR). The CI-MPR is also known as the insulin-like growth factor II receptor, a multi-functional protein implicated in tumour suppression.
GrpE nucleotide exchange factor, head (GrpE_head)
Type: Homologous_superfamily

In prokaryotes, the nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK . The DnaK reaction cycle involves rapid peptide binding and release, which is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK, which enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK, which is required for peptide release. In eukaryotes, GrpE is essential for mitochondrial Hsp70 function, however the cytosolic Hsp70 homologues are GrpE-independent.

GrpE binds as a homodimer to the ATPase domain of DnaK, and may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains, the N-terminal coiled coil domain, which may facilitate peptide release, and the C-terminal head domain, which forms part of the contact surface with the ATPase domain of DnaK. The head domain is comprised of six short β strands with a limited hydrophobic core.
Attachment protein shaft domain superfamily (Attachment_protein_shaft_sf)
Type: Homologous_superfamily

The attachment proteins in adenoviruses and reoviruses display structural similarity, indicating similar cell-surface receptor binding strategies, even though these viruses differ from one another in design, capsid composition and genome composition . The dsDNA adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised, while the dsRNA reoviruses are responsible for mild respiratory or gastrointestinal infections.
Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II (Transketo_C/PFOR_II)
Type: Homologous_superfamily

Transketolase C-terminal-like domains can be found in a number of different enzymes, including the C-terminal domain of the pyruvate dehydrogenase E1 component , the C-terminal domain of branched-chain alpha-keto acid dehydrogenases , and domain II of pyruvate-ferredoxin oxidoreductase (PFOR) . Structural studies reveal this domain to comprise of three layers α/β/α. The mixed β sheet consists of five strands in the order 13245, where strand 1 is antiparallel to the others. This domain has been proposed as a regulatory molecule binding site in transketolase .
L-fucose isomerase, N-terminal/central domain superfamily (Fucose_isomerase_N/cen_sf)
Type: Homologous_superfamily

L-fucose isomerase (

) converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucose metabolism using Mn2+ as a cofactor. The enzyme is a hexamer, forming the largest structurally known ketol isomerase, and has no sequence or structural similarity with other ketol isomerases. L-fucose isomerase is composed of three domains, the N-terminal, central and C-terminal domains. The N-terminal and central domains have a similar topology, consisting of three layers (α/β/α) each. The N-terminal domain has a parallel β-sheet of five strands in the order S2, S1, S3, S4, S5, while the central domain has a parallel β-sheet of four strands in the order S2, S1, S3, S4 .
Iron hydrogenase (Fe_hydrogenase)
Type: Homologous_superfamily

The iron-only hydrogenases (

) catalyse the two-electron reduction of two protons to yield dihydrogen, as part of an energy cycle. Fe-only hydrogenases are restricted to strictly anaerobic microbes, and are often very sensitive to molecular oxygen. The cytoplasmic monomeric Fe hydrogenases are involved in hydrogen production, while the periplasmic, heterodimeric Fe hydrogenases are involved in hydrogen uptake. Fe hydrogenases consist of two, intertwined domains, the catalytic domain and the larger subunit C domain . The larger subunit C domain can be divided into three subdomains. There are five distinct metal clusters, one in the catalytic domain. This superfamily represents the two intertwined domains, the catalytic domain and the large subunit C domain.
Green fluorescent protein (GFP)
Type: Homologous_superfamily

The green fluorescent-like protein family consists of fluorescent proteins and non-fluorescent chromoproteins, derived from several species of Cnidarians, as well as certain diazotrophic bacteria . These proteins range in their absorption wavelength maximum, and are often classified by their colour: green, yellow, red and purple-blue. These colour differences arise from changes in the structure of the chromophore, which is generated internally by auto-catalysis. The chromophore comprises Ser65-Tyr66-Gly67 in Aequorea victoria (Jellyfish), which forms a five-member ring after its modification. In the bioluminescent organism A. victoria, GFP acts to transform the blue light emitted from aequorin into green light. However, most organisms with GFP-like molecules are not bioluminescent, and in some cases are not even fluorescent. These proteins all display a β-can structure, which surrounds the chromophore and acts to shield it against quenching agents.
Signal recognition particle, SRP9/SRP14 subunit (Signal_recog_particle_SRP9/14)
Type: Homologous_superfamily

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 superfamily represents both the 9kDa SRP9 and the 14kDa SRP14 components. Both SRP9 and SRP14 have the same (β)-α-β(3)-α fold. The heterodimer has pseudo two-fold symmetry and is saddle-like, consisting of a curved six-stranded β-sheet that has four helices packed on the convex side and an exposed concave surface lined with positively charged residues. The SRP9/SRP14 heterodimer is essential for SRP RNA binding, mediating the pausing of synthesis of ribosome associated nascent polypeptides that have been engaged by the targeting domain of SRP .
K homology domain superfamily, prokaryotic type (KH_sf_prok-type)
Type: Homologous_superfamily

The K homology domain is a common RNA-binding motif present in one or multiple copies in both prokaryotic and eukaryotic regulatory proteins. The KH motifs may act cooperatively to bind RNA in the case of multiple motifs, or independently in the case of single KH motif proteins. Prokaryotic (pKH) and eukaryotic (eKH) KH domains share a KH-motif, but have different topologies. The pKH domain has been found in a number of proteins, including the N-terminal domain of the S3 ribosomal protein , the C-terminal domain of Era GTPase and the two C-terminal domains of the NusA transcription factor . The structure of the pKH domain consists of a two-layer α/β fold in the arrangement α/β(2)/α/β.
Elongation factor G, domain III (EFG_III)
Type: Domain

EF2 (or EFG) participates in the elongation phase of protein synthesis by promoting the GTP-dependent translocation of the peptidyl tRNA of the nascent protein chain from the A-site (acceptor site) to the P-site (peptidyl tRNA site) of the ribosome. EF2 also has a role after the termination phase of translation, where, together with the ribosomal recycling factor, it facilitates the release of tRNA and mRNA from the ribosome, and the splitting of the ribosome into two subunits . EF2 is folded into five domains, with domains I and II forming the N-terminal block, domains IV and V forming the C-terminal block, and domain III providing the covalently-linked flexible connection between the two. Domains III and V have the same fold (although they are not completely superimposable and domain III lacks some of the superfamily characteristics), consisting of an α/β sandwich with an antiparallel β-sheet in a (β/α/β)x2 topology . This double split β/α/β fold is also seen in a number of ribonucleotide binding proteins. It is the most common motif occurring in the translation system and is referred to as the ribonucleoprotein (RNP) or RNA recognition (RRM) motif.
Hydroxymethylglutaryl-CoA reductase, class I/II, NAD/NADP-binding domain superfamily (HMG_CoA_Rdtase_NAD(P)-bd_sf)
Type: Homologous_superfamily

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This superfamily represents the NADP or NAD binding S-domain found in class I and II enzymes, respectively. The S-domain has the same structural fold in both classes of enzymes, consisting of an α/β sandwich with antiparallel β sheets, with a (β/α/β)x2 topology .
Methyl-coenzyme M reductase, ferredoxin-like fold (Me_CoM_Rdtase_Fd-like_fold)
Type: Homologous_superfamily

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This superfamily represents a domain with a ferredoxin-like fold decorated with additional secondary structures that is found in all three subunits, alpha, beta and gamma. This fold consists of an α/β sandwich with an anti-parallel β-sheet with a duplicated β-α-β topology .
DNA-directed RNA polymerase, RBP11-like dimerisation domain (RBP11-like_dimer)
Type: Domain

RNA polymerase (RNAP) II, which is responsible for all mRNA synthesis in eukaryotes, consists of 12 subunits. Subunits Rpb3 and Rpb11 form a heterodimer that is functionally analogous to the archaeal RNAP D/L heterodimer, and the prokaryotic RNAP alpha subunit homodimer. In each case, they play a key role in RNAP assembly by forming a platform on which the catalytic subunits (eukaryotic Rpb1/Rpb2, and prokaryotic beta/beta') can interact . These different subunits share regions of homology. Rpb11 contains a domain (Rpb11-like domain) that is required for dimerisation, and binds to a homologous region on Rpb3. The Rpb11-like domain in Rpb11 and archaeal L subunits is contiguous, whereas in Rpb3, archaeal D, and prokaryotic alpha subunits (

), the Rpb11-like domain is interrupted by an insert domain (

). In the prokaryotic RNAP alpha subunit, the Rpb11-like domain and the insert domain form two subregions of the N-terminal domain.

The structure of the Rpb11-like domain consists of a two-layer α/β fold consisting of β(2)-α-β(2)-α. Rpb3 and Rpb11 in yeast RNAP have been shown to share a high degree of sequence and structural similarity to the alpha subunit of bacterial RNAP .
Large ribosomal subunit protein bL9/RNase H1, N-terminal (Ribosomal_bL9/RNase_H1_N)
Type: Homologous_superfamily

The N-terminal domain of the large ribosomal subunit protein bL9 (previously known as ribosomal protein L9) is a regulatory RNA-binding module that binds to 23rRNA. bL9 is composed of two domains and functions as a structural protein in the large subunit of the ribosome.

The N-terminal domain of eukaryotic RNase HI, which is lacking in retroviral and prokaryotic enzymes, shows a striking structural similarity to the bL9 N-terminal domain, and may also function as a regulatory RNA-binding module. Eukaryotic RNases HI possess either one or two copies of the small N-terminal domain, in addition to the well-conserved catalytic RNase H domain. RNase HI belongs to the family of ribonuclease H enzymes that recognise RNA:DNA hybrids and degrade the RNA component.
Coatomer/calthrin adaptor appendage, C-terminal subdomain (Coatomer/calthrin_app_sub_C)
Type: Homologous_superfamily

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer .

The alpha and beta2 adaptor subunits can each be divided into a trunk domain and the appendage domain (or ear domain), separated by a linker region. Clathrin polymerisation is promoted by its binding to the beta2 appendage and hinge domains. The alpha appendage domain interacts with a number of accessory proteins, including eps15, epsin, amphiphysin, AP180, auxilin, numb, and Dab2, thereby regulating the translocation of these proteins to the bud site.
Hydroxymethylglutaryl-CoA reductase, class I/II, substrate-binding domain superfamily (HMG_CoA_Rdtase_sub-bd_dom_sf)
Type: Homologous_superfamily

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This superfamily represents the substrate-binding L-domain found in class I and II enzymes. The L-domain has the same structural fold in both classes of enzymes, and is unique to HMG-CoA reductases. Its topology resembles a prism, with a central α helix surrounded by three α/β subdomains forming three roughly triangular walls .
Growth factor receptor cysteine-rich domain superfamily (Growth_fac_rcpt_cys_sf)
Type: Homologous_superfamily

This growth factor receptor domain is a cysteine-rich region that is found in a variety of eukaryotic proteins that are involved in the mechanism of signal transduction by receptor tyrosine kinases. Proteins containing the growth factor receptor domain include the insulin-like growth factor-binding proteins (IGFBP) , the type-1 insulin-like growth-factor receptor (IGF-1R) , and members of the epidermal growth factor (EGF) receptor family , such as the receptor protein-tyrosine kinase Erbb-3 (ErbB3) . The general structure of the growth factor receptor domain is a disulphide-bound fold containing a β-hairpin with two adjacent disulphides.

IGFBPs control the distribution, function and activity of insulin-like growth factors (IGFs) IGF-I and IGF-II, which are key regulators of cell proliferation, differentiation and transformation. All IGFBPs share a common domain organisation, where the highest conservation is found in the N-terminal Cys-rich IGF-binding domain. The N-terminal domain contains 10-12 conserved cysteine residues.

IGF-1R is a member of the tyrosine-kinase receptor superfamily that is involved in both normal growth and development and malignant transformation. The Cys-rich domain is flanked by two L-domains, and together they contribute to hormone binding and ligand specificity, even though they do not bind ligand directly. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain.
Carbohydrate binding module family 10 (CBM10)
Type: Domain

Plant cell wall hydrolases from aerobic microorganisms generally have a modular structure consisting of a catalytic domain linked to one or more carbohydrate-binding modules (CBMs). CBMs function to attach the enzyme to the polymeric substrate, thereby increasing the catalytic activity. Most CBMs bind cellulose and are referred to as cellulose-binding domains (CBDs), while some can also bind xylan.
Vpu protein cytoplasmic domain superfamily (Vpu_cyt_dom_sf)
Type: Homologous_superfamily

The human immunodeficiency virus type 1 Vpu transmembrane protein is required for the induction of degradation human CD4 receptor degradation in the endoplasmic reticulum, and for the enhancement of virus particle release from the plasma membrane of infected cells. The cytoplasmic domain of Vpu directly interacts with the CD4 receptor, targeting it for proteasome degradation . The cytoplasmic domain encompasses the C-terminal half of the 81-residue protein, and is comprised of a few helical turns without an apparent hydrophobic core .
Calreticulin/calnexin, P domain superfamily (Calreticulin/calnexin_P_dom_sf)
Type: Homologous_superfamily

The type-I integral membrane protein calnexin (CNX) and its soluble paralog calreticulin (CRT) are members of a family of molecular chaperones that function in the endoplasmic reticulum (ER) of eukaryotic cells. These calcium-binding proteins are lectins that bind newly synthesised N-linked glycoproteins to help promote efficient folding and oligomeric assembly. The chaperones act to retain the glycoproteins in the ER while they are still incompletely folded, ensuring that the ER quality control machinery can dispose of misfolded glycoproteins. The family of molecular chaperones are conserved among plants, fungi, and animals.
Fungal dockerin domain superfamily (Dockerin_dom_fun_sf)
Type: Homologous_superfamily

In anaerobic microorganisms, the degradation of plant cell walls in order to recycle the photosynthetically fixed carbon is carried out by a multifunctional complex termed the cellulosome.
This consists of a number of independent enzyme components, each of which contains a conserved dockerin domain, which functions to bind the enzyme to a cohesin domain within the protein scaffoldin protein .