SII-SWORD/CoKE huggingface dataset:
Phosducin, N-terminal domain superfamily (Phosducin_N_dom_sf)
Type: Homologous_superfamily

The outer and inner segments of vertebrate rod photoreceptor cells contain phosducin, a soluble phosphoprotein that complexes with the beta/gamma-subunits of the GTP-binding protein, transducin. Light-induced changes in cyclic nucleotide levels modulate the phosphorylation of phosducin by protein kinase A . The protein is thought to participate in the regulation of visual phototransduction or in the integration of photo-receptor metabolism. Similar proteins have been isolated from the pineal gland and it is believed that the functional role of the protein is the same in both retina and pineal gland .

This superfamily represents the N-terminal domain of phosducin. Together with the C-terminal domain, it covers one side and the top of the seven-bladed β propeller of Gt beta gamma. The binding of phosducin induces a distinct structural change in the β propeller of Gt beta gamma, such that a small cavity opens up between blades 6 and 7 . Binding of phosducin results in sequestration of beta gamma from the membrane to the cytosol and turns off the signal-transduction cascade. Regulation of this membrane association/dissociation switch of Gt beta gamma by phosducin may be a general mechanism for attenuation of G protein coupled signal transduction cascades.
Bacteriophage T4, Gp59, helicase assembly protein domain superfamily (Phage_T4_Gp59_dom_sf)
Type: Homologous_superfamily

The Bacteriophage T4 gene 59 helicase assembly protein (Gp59) is required for recombination-dependent DNA replication and repair, which is the predominant mode of DNA replication in the late stage of T4 infection. Gp59 accelerates the loading of the T4 gene 41 helicase during DNA synthesis by the T4 replication system in vitro. This protein binds to both T4 gene 41 helicase and T4 gene 32 single-stranded DNA binding protein, and to single and double-stranded DNA .

The structure of Gp59 helicase assembly protein reveals a novel α-helical bundle fold with two domains of similar size. Surface residues are predominantly basic (pI 9.37) with clusters of acidic residues but exposed hydrophobic residues suggest sites for potential contact with DNA and with other protein molecules . The N-terminal domain shares structural homology with the high mobility group (HMG) proteins from eukaryotic organisms and it has been suggested that it plays a role in duplex DNA binding ahead of the fork. The C-terminal domain interacts with the helicase (T4 gp41) and with SSB (single-stranded binding protein T4 gp32) .
Phosphoglycolate phosphatase-like, domain 2 (PGP-like_dom2)
Type: Homologous_superfamily

Phosphoglycolate phosphatase (PGP) is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In Ralstonia eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO . In E. coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the E. coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes.

This entry represents an α-helical orthogonal bundle found towards the N terminus of phosphoglycolate phosphatase and related proteins.
Copper chaperone GriE/MELC1 superfamily (GriE/MELC1_sf)
Type: Homologous_superfamily

This superfamily represents the 2-layer α/β sandwich domain of tyrosinase co-factor MELC1 and copper chaperone GriE .

The melanin operon (melC) of Streptomyces antibioticus contains two genes, melC1 and melC2 (apotyrosinase). It is thought that MelC1 forms a transient binary complex with the downstream apotyrosinase MelC2 to facilitate the incorporation of copper ion and the secretion of tyrosinase indicating that MelC1 is a chaperone for the apotyrosinase MelC2 .
Ribosome modulation factor domain superfamily (RMF_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain of ribosome modulation factors (RMF). They associate with 70s ribosomes and convert them to a dimeric form (100S ribosomes) which appear during the transition from the exponential growth phase to the stationary phase of Escherichia coli cells .

It has been proposed that RMF mediates the formation of a 'storage ribosome', the 100S particle, in stationary phase by inactivating excess ribosomes to protect them from degradation and to maintain the required balance between the concentrations of ribosomes and protein synthesis factors in order to maintain translational elongation efficiency .
SecY domain superfamily (SecY_dom_sf)
Type: Homologous_superfamily

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion . The structure of the Escherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic domains . Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices.

This superfamily represents the structural domain of SecY .
YejL-like superfamily (YejL_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain of the UPF0352 family of proteins, which have not known function.
TTHA0068-like superfamily (TTHA0068_sf)
Type: Homologous_superfamily

This superfamily represents a structural domain found in the DUF309 family of proteins of unknown function.
SP1917 domain superfamily (SP1917_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain found in protein SP1917 and other members of the UCP033199 family of uncharacterised proteins.
Thiol:disulphide interchange protein DsbA/DsbL (DsbA/DsbL)
Type: Family

Bacterial Disulfide bond forming (Dsb) proteins facilitate proper folding and disulfide bond formation of periplasmic and secreted proteins .

Thiol:disulphide interchange proteins DsbA and DsbL are involved in disulfide-bond formation . They act by transferring its disulfide bond to other proteins and are reduced in the process. DsbA is required for disulfide bond formation in some periplasmic proteins such as PhoA or OmpA and is reoxidised by DsbB . DsbA is a monomeric thiol disulfide oxidoreductase protein containing a redox active CXXC motif imbedded in a TRX fold. It is involved in the oxidative protein folding pathway in prokaryotes, and is the strongest thiol oxidant known, due to the unusual stability of the thiolate anion form of the first cysteine in the CXXC motif . The highly unstable oxidized form of DsbA directly donates disulfide bonds to reduced proteins secreted into the bacterial periplasm. This rapid and unidirectional process helps to catalyze the folding of newly-synthesized polypeptides. To regain catalytic activity, reduced DsbA is then reoxidized by the membrane protein DsbB, which generates its disulfides from oxidized quinones, which in turn are reoxidized by the electron transport chain . DsbL is reoxidised by DsbI; DsbL and DsbI represent a second redox couple in some bacteria for specific substrates .
Bifunctional cytochrome P450/NADPH--cytochrome P450 reductase (Bifunctional_P450_P450_red)
Type: Family

Bifunctional cytochrome P450/NADPH--cytochrome P450 reductase (also known as P450foxy) is a fused protein of cytochrome P450 and its reductase . It is a fatty acid (FA) monooxygenase that is characterised by self-sufficient catalysis and high turnover numbers due to the fused structure . Its reductase domain is required for electron transfer from NADP to cytochrome P450 .
NADPH-cytochrome P450 reductase (P450R)
Type: Family

This group represents the NADPH--cytochrome P450 reductase (CPR) from eukaryotes. CPR is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5 .

Interestingly, animals harbour a single CPR gene, while higher plants have multiple CPRs with as many as three in Populus tricocarpa and Oryza sativa . In comparison with other CPRs, plant CPRs often possess long N-terminal membrane-spanning domains .
D-amino-acid oxidase (DAO)
Type: Family

D-Amino acid oxidase (DAO or DAAO) is a flavin adenine dinucleotide (FAD)-containing flavoproteins that catalyse the oxidative deamination of d-amino acids with oxygen to generate the corresponding 2-oxo acids along with hydrogen peroxide and ammonia. It displays broad substrate specificity and acts on several neutral and basic d-amino acids, such as d-Ser and d-Ala .
NADP-dependent oxidoreductase domain (NADP_OxRdtase_dom)
Type: Domain

The aldo-keto reductase family includes a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and many others . All possess a similar structure, with a β-α-β fold characteristic of nucleotide binding proteins . The fold comprises a parallel β8/α8 barrel, which contains a novel NADP-binding motif. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the β-sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones .

Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases .

Some proteins of this entry contain a K+ ion channel beta chain regulatory domain; these are reported to have oxidoreductase activity .

This entry represents the NADP-dependent oxidoreductase domain found in these proteins.
DNA polymerase, palm domain superfamily (DNA_pol_palm_dom_sf)
Type: Homologous_superfamily

DNA is the biological information that instructs cells how to exist in an ordered fashion: accurate replication is thus one of the most important events in the life cycle of a cell. This function is performed by DNA- directed DNA-polymerases

) by adding nucleotide triphosphate (dNTP) residues to the 5'-end of the growing chain of DNA, using a complementary DNA chain as a template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used for the de novo synthesis of a DNA chain. Even though there are 2 different methods of priming, these are mediated by 2 very similar polymerases classes, A and B, with similar methods of chain elongation.

A number of DNA polymerases have been grouped under the designation of DNA polymerase family B. Six regions of similarity (numbered from I to VI) are found in all or a subset of the B family polymerases. The most conserved region (I) includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known, however, it has been suggested that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain , a DNA binding domain, and binding domains for both dNTP's and pyrophosphate .
Heat shock protein Hsp33, helix hairpin bin domain superfamily (Hsp33_helix_hairpin_bin_dom_sf)
Type: Homologous_superfamily

Hsp33 is a molecular chaperone, distinguished from all other known chaperones by its mode of functional regulation. Its activity is redox regulated. Hsp33 is a cytoplasmically localized protein with highly reactive cysteines that respond quickly to changes in the redox environment. Oxidizing conditions like H
2
O
2
cause disulphide bonds to form in Hsp33, a process that leads to the activation of its chaperone function. In normal (reducing) cytosolic conditions, four conserved Cys residues are coordinated by a Zn ion. Hsp33 is homodimeric in its functional form .

This superfamily represents a helix hairpin bin domain found in Hsp33. This domain folds into three helices that pack on the other subunit of the Hsp33 dimer .
Chloramphenicol acetyltransferase-like domain superfamily (CAT-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain characteristic of trimeric enzymes with the active sites being located in between subunits, including chloramphenicol acetyltransferase.

Chloramphenicol acetyltransferase (CAT) catalyses the acetyl-CoA dependent acetylation of chloramphenicol, resulting in the inactivation of the antibiotic. The crystal structure of the type III enzyme from Escherichia coli with chloramphenicol bound has been determined. CAT is a trimer of identical subunits (monomer Mr 25,000) and the trimeric structure is stabilised by a number of hydrogen bonds, some of which result in the extension of a β-sheet across the subunit interface. Chloramphenicol binds in a deep pocket located at the boundary between adjacent subunits of the trimer, such that the majority of residues forming the binding pocket belong to one subunit while the catalytically essential histidine belongs to the adjacent subunit. His195 is appropriately positioned to act as a general base catalyst in the reaction, and the required tautomeric stabilisation is provided by an unusual interaction with a main-chain carbonyl oxygen .
HAD superfamily (HAD_sf)
Type: Homologous_superfamily

The haloacid dehydrogenase (HAD) superfamily includes phosphatases, phosphonatases, P-type ATPases, beta-phosphoglucomutases, phosphomannomutases, and dehalogenases, which are involved in a variety of cellular processes ranging from amino acid biosynthesis to detoxification .

Crystal structures of proteins from the HAD superfamily show that these proteins all share a conserved α/β-domain classified as a hydrolase fold, which is similar to the Rossmann fold . This conserved domain usually contains an insertion (sub)domain. For example, the crystal structure of a phosphoglycolate phosphatase from Thermoplasma acidophilum revealed two distinct domains, a larger core domain and a smaller cap domain. The large domain is composed of a centrally located five-stranded parallel β-sheet with strand order S10, S9, S8, S1, S2 and a small β-hairpin, strands S3 and S4. This central sheet is flanked by a set of three α-helices on one side and two helices on the other. The topology of the large domain is conserved; however, structural variation is observed in the smaller domain among the different functional classes of the haloacid dehalogenase superfamily.
Transcription regulator SKI/SnoN (Tscrpt_reg_SKI_SnoN)
Type: Family

This entry represents the SKI/SnoN family of proteins, which are the products of the oncogenic sno gene. This gene was identified based on its homology to
v-ski
, the transforming component of the Sloan-Kettering virus. Both Ski and SnoN are potent negative regulators of TGF-beta . Overexpression of Ski or SnoN results in oncogenic transformation of avian fibroblasts; however it may also result in terminal differentiation and therefore the Ski/SnoN mechanism of action is thought to be complex .

These proteins do not have catalytic or DNA-binding activity and therefore function primarily through interaction with other proteins, acting as transcriptional cofactors. Despite their lack of DNA-binding ability, their primary function is related to transcriptional regulation, in particular the negative regulation of TGF-beta signalling . Ski/SnoN interact concurrently with co-Smad and R-Smad and in doing so block the ability of the Smad complexes to activate transcription of the TGF-beta target genes . Binding of Ski/SnoN may additionally stabilise the Smad heteromer on DNA, therefore preventing further binding of active Smad complexes . As Smad complexes critically mediate the inhibitory signals of TGF-beta in epithelial cells, high levels of SKI/SnoN may promote cell proliferation. They repress gene transcription recruiting diverse corepressors and histone deacetylases and stablish cross-regulatory mechanisms with TGF-beta/Smad pathway that control the magnitude and duration of TGF-beta signals. The alteration in regulatory processes may lead to disease development .

High levels of SnoN have been shown to stabilise p53 with a resultant increase in premature senescence. SnoN interacts with the PML protein and is then recruited to the PML nuclear bodies, resulting in stabilisation of p53 and premature senescence .
Hepatocyte nuclear factor 1, N-terminal domain superfamily (HNF1_dimer_N_dom_sf)
Type: Homologous_superfamily

The N-terminal dimerisation domain of the transcriptional activator hepatocyte nuclear factor 1 is essential for DNA binding and association of the transcriptional coactivator, DCoH (dimerization cofactor of HNF-1). This domain forms a unique four-helical bundle which is largely conserved when dimerisation occurs .
Type IV secretion system, VirB5-domain (T4SS_VirB5-domain)
Type: Homologous_superfamily

VirB5 proteins are an essential component of most type IV secretion systems. VirB5/TraC is a single domain protein consisting of a three helix bundle and a loose globular appendage . Structural and functional studies indicate that VirB5 proteins participate in protein-protein interactions important for pilus assembly and function.
PsbQ-like domain superfamily (PsbQ-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a four helix up-down bundle domain found in a number of proteins including PsbQ from chloroplast and cyanobacterial photosystem II, and cyclocphilins involved in the assembly and maintenanace of phtosystem II .
Salmonella invasion protein A, C-terminal actin-binding domain superfamily (SipA_actin-bd_C_sf)
Type: Homologous_superfamily

Salmonella invasion protein A (SipA) is a virulence factor that is translocated into host cells by a type III secretion system. In the host cell it binds to actin, stimulates actin polymerisation and counteracts F-actin destabilising proteins. This contributes towards cytoskeletal rearrangements that allow the entry of the pathogen into the host cell .

The actin-binding domain forms a heart-shaped helical structure that appears to be unrelated to that of other actin-binding domains . Disordered regions are present on both sides of the structural domain, forming nonglobular arms. SipA polymerises actin by stapling filaments with these nonglobular arms.
Salmonella invasion protein A, chaperone-binding (SipA_chaperone-bd)
Type: Homologous_superfamily

Salmonella invasion protein A (SipA) is a virulence factor that is translocated into host cells by a type III secretion system. In the host cell it binds to actin, stimulates actin polymerisation and counteracts F-actin destabilising proteins. This contributes towards cytoskeletal rearrangements that allow the entry of the pathogen into the host cell .

The chaperone-binding domain of SipA consists of a globular domain, represented by this entry, and an adjacent nonglobular polypeptide . Both of these elements are necessary for chaperone binding to occur. The globular domain is composed of eigth α helices arranged so that six amphipathic helices surround a predominantly hydrophobic helix in the middle.
Glycoside hydrolase, family 49, N-terminal domain (Glyco_hydro_49_N_dom)
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.

Dextranase (

) and isopullulanase (

) are members of glycoside hydrolase family 49 (

). Dextranase hydrolyses alpha-1,6-glycosidic bonds in dextran polymers.

The N-terminal domain of these enzymes forms a β-sandwich structure that is similar to the immunoglobulin fold but contains two extra strands.
.
S-adenosyl-l-methionine hydroxide adenosyltransferase, C-terminal domain superfamily (SAM_OH_AdoTrfase_C_sf)
Type: Homologous_superfamily

The S-adenosyl-L-methionine (SAM) hydroxide adenosyltransferase family groups several fluorinase and chlorinase enzymes whose common feature is that they mediate nucleophilic reactions of their respective halide ions to the C-5' carbon of SAM . These enzymes utilise a rigorously conserved amino acid side chain triad (Asp-Arg-His) which may have a role in activating water to hydroxide ion. Structural studies indicate that the protein is a homotrimer, with each monomer being composed of N- and C-terminal domains . The N-terminal domain has a central seven-stranded β-sheet, which combines parallel and antiparallel strands sandwiched between α-helices. The C-terminal domain forms a β-barrel with a greek-key topology. SAM is bound at the interface between the C-terminal domain of one monomer and the N-terminal domain of the neighbouring monomer, with a total of three molecules bound by the trimer. This group of proteins, which are predominantly found in prokaryotes, used to be known as DUF62 .

This superfamily represents the C-terminal domain of these proteins.
S-adenosyl-l-methionine hydroxide adenosyltransferase, N-terminal domain superfamily (SAM_OH_AdoTrfase_N_sf)
Type: Homologous_superfamily

The S-adenosyl-L-methionine (SAM) hydroxide adenosyltransferase family groups several fluorinase and chlorinase enzymes whose common feature is that they mediate nucleophilic reactions of their respective halide ions to the C-5' carbon of SAM . These enzymes utilise a rigorously conserved amino acid side chain triad (Asp-Arg-His) which may have a role in activating water to hydroxide ion. Structural studies indicate that the protein is a homotrimer, with each monomer being composed of N- and C-terminal domains . The N-terminal domain has a central seven-stranded β-sheet, which combines parallel and antiparallel strands sandwiched between α-helices. The C-terminal domain forms a β-barrel with a greek-key topology. SAM is bound at the interface between the C-terminal domain of one monomer and the N-terminal domain of the neighbouring monomer, with a total of three molecules bound by the trimer. This group of proteins, which are predominantly found in prokaryotes, used to be known as DUF62 .

This entry represents the N-terminal domain of these proteins.