SII-SWORD/CoKE huggingface dataset:
Formiminotransferase, C-terminal subdomain superfamily (Formiminotransferase_C_sf)
Type: Homologous_superfamily

The formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD) forms a homodimer, with each protomer being comprised of two subdomains. The formiminotransferase domain has an N-terminal subdomain that is made up of a six-stranded mixed β-pleated sheet and five α helices, which are arranged on the external surface of the β sheet. This, in turn, faces the β-sheet of the C-terminal subdomain to form a double β-sheet layer. The two subdomains are separated by a short linker sequence, which is not thought to be any more flexible than the remainder of the molecule. The substrate is predicted to form a number of contacts with residues found in both the N-terminal and C-terminal subdomains . In humans, deficiency of this enzyme results in a disease phenotype .

This entry represents the C-terminal subdomain superfamily of the formiminotransferase.
Amyloidogenic glycoprotein, amyloid-beta peptide superfamily (Amyloid_glyco_Abeta_sf)
Type: Homologous_superfamily

Amyloid-beta precursor protein (APP, or A4) is associated with Alzheimer's disease (AD), because one of its breakdown products, amyloid-beta (A-beta), aggregates to form amyloid or senile plaques . Mutations in APP or in proteins that process APP have been linked with early-onset, familial AD. Individuals with Down's syndrome carry an extra copy of chromosome 21, which contains the APP gene, and almost invariably develop amyloid plaques and Alzheimer's symptoms.

APP is important for the neurogenesis and neuronal regeneration, either through the intact protein, or through its many breakdown products . APP consists of a large N-terminal extracellular region containing heparin-binding and copper-binding sites, Kunitz domain, E2 domain, a short hydrophobic transmembrane domain, and a short C-terminal intracellular domain. The N-terminal region is similar in structure to cysteine-rich growth factors and appears to function as a cell surface receptor, contributing to neurite growth, neuronal adhesion, axonogenesis and cell mobility . APP acts as a kinesin I membrane receptor to mediate the axonal transport of beta-secretase and presenilin 1. The N-terminal domain can regulate neurite outgrowth through its binding to heparin and collagen I and IV, which are components of the extracellular matrix. APP is also coupled to apoptosis-inducing pathways, and is involved in copper homeostasis/oxidative stress through copper ion reduction, where copper-metallated APP induces neuronal death . The C-terminal intracellular domain appears to be involved in transcription regulation through protein-protein interactions. APP can promote transcription activation through binding to APBB1/Tip60, and may bind to the adaptor protein FE65 to transactivate a wide variety of different promoters.

APP can be processed by different sets of enzymes:

In the non-amyloidogenic (non-plaque-forming) pathway, APP is cleaved by alpha-secretase to yield a soluble N-terminal sAPP-alpha (neuroprotective) and a membrane-bound CTF-alpha. CTF-alpha is broken-down by presenilin-containing gamma-secretase to yield soluble p3 and membrane-bound AICD (nuclear signalling).

In the amyloidogenic pathway (plaque-forming), APP is broken down by beta-secretase to yield soluble sAPP-beta and membrane-bound CTF-beta. CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact.

This entry represents the amyloid-beta peptide (A-beta) superfamily, which originates as a breakdown product from the cleavage of amyloid-beta precursor protein (APP, or A4), an integral, glycosylated membrane brain protein.
Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily (Nuc_rcpt_coact_CREBbp_sf)
Type: Homologous_superfamily

This entry represents the interlocking domain superfamily of the eukaryotic nuclear receptor coactivators CREBP and p300. The interlocking domain forms a 3-helical non-globular array that forms interlocked heterodimers with its target.

Nuclear receptors are ligand-activated transcription factors involved in the regulation of many processes, including development, reproduction and homeostasis. Nuclear receptor coactivators act to modulate the function of nuclear receptors. Coactivators associate with promoters and enhancers primarily through protein-protein contacts to facilitate the interaction between DNA-bound transcription factors and the transcription machinery. Many of these coactivators are structurally related, including CBP (CREB-binding protein) and p300 . CBP and p300 both have histone acetyltransferase activity (

). CBP/p300 proteins function synergistically to activate transcription, acting to remodel chromatin and to recruit RNA polymerase II and the basal transcription machinery. CBP is required for proper cell cycle control, differentiation and apoptosis. The interaction of CBP/p300 with transcription factors involves several small domains. The IBiD domain in the C-terminal of CBP is responsible for CBP interaction with IRF-3, as well as with the adenoviral oncoprotein E1A, TIF-2 coactivator, and the IRF homologue KSHV IRF-1 .
Protein of unknown function DUF1780, putative endonuclease superfamily (DUF1780_sf)
Type: Homologous_superfamily

This is a superfamily 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.
Formaldehyde-activating enzyme superfamily (HCHO-activating_enzyme_sf)
Type: Homologous_superfamily

This superfamily 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.
Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily (Nuc_rcpt_coact_Ncoa_int_sf)
Type: Homologous_superfamily

This entry represents the interlocking domain superfamily of the eukaryotic nuclear receptor coactivators Ncoa1, Ncoa2 and Ncoa3. The interlocking domain forms a 3-helical non-globular array that forms interlocked heterodimers with its target.

Nuclear receptors are ligand-activated transcription factors involved in the regulation of many processes, including development, reproduction and homeostasis. Nuclear receptor coactivators act to modulate the function of nuclear receptors. Coactivators associate with promoters and enhancers primarily through protein-protein contacts to facilitate the interaction between DNA-bound transcription factors and the transcription machinery. In addition to their role as coactivators of various nuclear receptors, Ncoa1 and Ncoa3 both have histone acetyltransferase activity (

), but Ncoa2 does not .
NEDD8-activating enzyme E1 catalytic subunit, C-terminal (NEDD8-ac_enz1_catalyticsu_C)
Type: Homologous_superfamily

E1 and E2 enzymes play a central role in ubiquitin and ubiquitin-like protein transfer cascades. This is an E2 binding domain that is found on NEDD8 activating E1 enzyme. The protein resembles ubiquitin, and recruits the catalytic core of the E2 enzyme Ubc12 in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains .
AF2212/PG0164-like superfamily (AF2212/PG0164-like_sf)
Type: Homologous_superfamily

This superfamily is composed of hypothetical bacterial proteins.
Capsid protein VP4 superfamily, Picornavirus (Capsid_VP4_sf_Picornavirus)
Type: Homologous_superfamily

This entry represents the VP4 coat protein superfamily found in Picornaviruses, small RNA-containing mammalian viruses such as Foot-and-mouth disease virus (FMDV) , Mengo encephalomyocarditis virus and Theiler's murine encephalomyelitis virus (strain DA) (TMEV) .
Hypothetical protein TM1506 (Hyp_TM1506)
Type: Homologous_superfamily

This family consist of hypothetical bacterial proteins.
Bacteriophage T4, Gp59, helicase assembly protein, C-terminal domain superfamily (Phage_T4_Gp59_C_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 C-terminal domain of the T4 gene 59 helicase assembly protein consists of seven α-helices with short intervening loops and turns; the surface of the domain contains large regions of exposed hydrophobic residues and clusters of acidic and basic residues. The hydrophobic region on the 'bottom' surface of the domain near the C-terminal helix binds the leading strand DNA, whilst the hydrophobic region on the, top, surface of the domain lies between the two arms of the fork DNA, allowing for T4 gene 41 helicase binding and assembly into a hexameric complex around the lagging strand .
Type-2 restriction enzyme NgoMIV superfamily (NgoMIV_sf)
Type: Homologous_superfamily

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This entry represents NgoMIV-type prokaryotic DNA restriction enzymes exhibiting an α/β structure, with a central region comprising a mixed six-stranded β-sheet with α-helices on each side. A long 'arm' protrudes out of the core of the domain between strands beta2 and beta3 and is mainly involved in the tetramerisation interface of the protein. These restriction enzymes recognise the double-stranded sequence GCCGGC and cleave after G-1 .
Protein-glutamine gamma-glutamyltransferase superfamily (Transglut_prok_sf)
Type: Homologous_superfamily

Protein-glutamine gamma-glutamyltransferase (also known as microbial transglutaminase, MTG) catalyses an acyl transfer reaction by means of a Cys-Asp diad mechanism, in which the gamma-carboxyamide groups of peptide-bound glutamine residues act as the acyl donors. The MTG molecule forms a single, compact domain belonging to the α+β folding class, containing 11 α-helices and 8 β-strands. The α-helices and the β-strands are concentrated mainly at the amino and carboxyl ends of the polypeptide, respectively. These secondary structures are arranged so that a β-sheet is surrounded by α-helices, which are clustered into three regions .
Cdc42 binding domain-like superfamily (Cdc42-bd-like_dom_sf)
Type: Homologous_superfamily

This entry represents the Cdc42 (a GTPase) binding domain superfamily. The domain is largely unstructured in the absence of Cdc42 . Proteins containing this domain include the probable tyrosine-protein kinase sid-3 and the activated CDC42 kinase 1.
D-Lysine 5,6-aminomutase alpha subunit superfamily (Lys-AminoMut_asu_sf)
Type: Homologous_superfamily

This domain superfamily is found in proteins involved in the 1,2 rearrangement of the terminal amino group of DL-lysine and of L-beta-lysine, using adenosylcobalamin (AdoCbl) and pyridoxal-5'-phosphate as cofactors. The structure is predominantly a PLP-binding TIM barrel domain, with several additional α-helices and β-strands at the N and C termini. These helices and strands form an intertwined accessory clamp structure that wraps around the sides of the TIM barrel and extends up toward the Ado ligand of the Cbl cofactor, providing most of the interactions observed between the protein and the Ado ligand of the Cbl, suggesting that its role is mainly in stabilising AdoCbl in the precatalytic resting state.
Vitellinogen, beta-sheet shell domain superfamily (Vitellinogen_b-sht_shell_sf)
Type: Homologous_superfamily

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved .

In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: lipovitellin-1, phosvitin, lipovitellin-2, and a von Willebrand factor type D domain (YGP40). Vitellinogens are post-translationally glycosylated and phosphorylated in the endoplasmic reticulum and Golgi complex of hepatocytes, before being secreted into the circulatory system to be taken up by oocytes. In the ovary, vitellinogens bind to specific Vtgr receptors on oocyte membranes to become internalised by endocytosis, where they are cleaved into yolk proteins by cathepsin D. YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.

The different yolk proteins have distinct roles. Phosvitins are important in sequestering calcium, iron and other cations for the developing embryo. Phosvitins are one of the most phosphorylated (10%) proteins in nature, the high concentration of phosphate groups providing efficient metal-binding sites in clusters . Lipovitellins are involved in lipid and metal storage, and contain a heterogeneous mixture of about 16% (w/w) noncovalently bound lipid, most being phospholipid. Lipovitellin-1 contains two chains, LV1N and LV1C .

This entry represents the β-sheet shell domain superfamily found in vitellinogen, which generally corresponds to the lipovitellin-2 peptide product. This domain consists of several large open β-sheets . It is often found C-terminal to

and

.
Methylene-tetrahydromethanopterin dehydrogenase, N-terminal domain superfamily (Methyl-teptahyd_DH_N_sf)
Type: Homologous_superfamily

Prokaryotic methylene-tetrahydromethanopterin dehydrogenase catalyses the dehydrogenation of methylene-tetrahydromethanopterin during growth on one-carbon compounds such as methanol. It can also catalyse the reversible dehydrogenation of methylene-tetrahydrofolate, though at much lower efficiency . The pterin domain of this protein is composed of two α-β segments found at the N- and C-terminal ends of the polypeptide respectivly. This entry represents the N-terminal segment of the pterin domain superfamily, with a core structure comprising three layers (α/β/α) in which the β-sheet contains four strands.
Glycoside hydrolase families 57, central domain (57_glycoside_trans_central)
Type: Homologous_superfamily

This domain is found in a set of hypothetical bacterial proteins that have a N-terminal domain related to the glycoside hydrolase family 57 (

). The exact function of this domain has not, as yet, been defined.
Penicillin-binding protein 4, C-terminal domain superfamily (Pen-bd_prot4_C_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found towards the C terminus of prokaryotic penicillin-binding protein 4.
Flavocytochrome c sulphide dehydrogenase, flavin-binding domain superfamily (FlavoCytC_S_DH_flav-bd_sf)
Type: Homologous_superfamily

This entry represents the flavin-binding domain superfamily of flavocytochrome c sulphide dehydrogenase (FCSD), enzymes found in sulphur-oxidising bacteria such as the purple phototrophic bacteria Chromatium vinosum . These enzymes are complexes of flavoprotein and a dihaem cytochrome that carry out hydrogen sulphide-dependent cytochrome C reduction. The dihaem cytochrome folds into two domains, each of which resembles mitochondrial cytochrome c, with the two haem groups bound to the interior of the subunit. The flavoprotein subunit has a glutathione reductase-like fold consisting of a beta(3,4)-α(3) core, and an α+β sandwich. The active site of the flavoprotein subunit contains a catalytically important disulphide bridge located above the pyrimidine portion of the flavin ring . Electrons are transferred from the flavin to one of the haem groups in the cytochrome. This entry represents a flavoprotein domain required for binding to flavin, and subsequent electron transfer.
Smaug, PHAT domain superfamily (PHAT_dom_sf)
Type: Homologous_superfamily

The PHAT (pseudo-HEAT analogous topology) domain assumes a structure consisting of a layer of three parallel helices packed against a layer of two antiparallel helices, into a cylindrical shaped five-helix bundle. It is found in the RNA-binding protein Smaug in insects, where it is essential for high-affinity RNA binding . Smaug is a translation regulator that binds to the 3'-UTR of specific mRNAs such as nanos (nos) and prevents their translation . The mammalian homologue Smaug 1 is thought to play a role in RNA granule formation and translation regulation in neurons . Another mammalian homologue Smaug 2 acts as a transcriptional repressor .
Glycoside hydrolase family 38, central domain superfamily (Glyco_hydro_38_cen_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily found in members of the glycosyl hydrolases families 38. This domain is found in the central region that adopts a structure consisting of three α helices, in an immunoglobulin/albumin-binding domain-like fold. The domain is predominantly found in the enzyme alpha-mannosidase .

Glycoside hydrolase family 38

comprises enzymes with only one known activity; alpha-mannosidase (

) (

).

Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.
RBP-J/Cbf11, DNA binding domain superfamily (RBP-J/Cbf11_DNA-bd_sf)
Type: Homologous_superfamily

This domain superfamily is found in RBP-J from human and Cbf11 from fission yeast. These proteins function as transcription factors . This domain adopts a β sandwich structure, with nine strands in two β-sheets, in a Greek-key topology, and allow for DNA binding .
KCNMB2, ball/chain domain superfamily (KCNMB2_ball/chain_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found in the cytoplasmic N terminus of KCNMB2, the beta-2 subunit of large conductance calcium and voltage-activated potassium channels. It is responsible for the fast inactivation of these channels .
Photosynthetic reaction centre, H subunit, N-terminal domain superfamily (Photo_RC_H_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain superfamily of the photosynthetic reaction centre H subunit, which includes the transmembrane domain and part of the cytoplasmic domain .

The photosynthetic apparatus in non-oxygenic bacteria consists of light-harvesting (LH) protein-pigment complexes LH1 and LH2, which use carotenoid and bacteriochlorophyll as primary donors . LH1 acts as the energy collection hub, temporarily storing it before its transfer to the photosynthetic reaction centre (RC) . Electrons are transferred from the primary donor via an intermediate acceptor (bacteriopheophytin) to the primary acceptor (quinine Qa), and finally to the secondary acceptor (quinone Qb), resulting in the formation of ubiquinol QbH2. RC uses the excitation energy to shuffle electrons across the membrane, transferring them via ubiquinol to the cytochrome bc1 complex in order to establish a proton gradient across the membrane, which is used by ATP synthetase to form ATP .

The core complex is anchored in the cell membrane, consisting of one unit of RC surrounded by LH1; in some species there may be additional subunits . RC consists of three subunits: L (light), M (medium), and H (heavy). Subunits L and M provide the scaffolding for the chromophore, while subunit H contains a cytoplasmic domain . In Rhodopseudomonas viridis, there is also a non-membranous tetrahaem cytochrome (4Hcyt) subunit on the periplasmic surface.
Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal domain superfamily (Fum_R/Succ_DH_flav-like_C_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily with a spectrin-repeat-like fold consisting of three helices in a closed bundle with a left-handed twist. This domain superfamily is found in the succinate dehydrogenase/fumarate reductase oxidoreductase family of proteins, such as:

L-aspartate oxidase (

), a flavoenzyme component of the bacterial quinolinate synthase system that catalyses the conversion of L-aspartate to oxaloacetate, the first step in the de novo biosynthesis of NAD+ .

Fumarate reductase, which is part of the quinol-fumarate reductase (QFR) respiratory complex that catalyses the terminal step of anaerobic respiration when fumarate acts as the terminal electron acceptor .

Succinate dehydrogenase (SQR;

), an iron-sulphur flavoenzyme from bacteria that is analogous to the mitochondrial respiratory complex II, forming part of the electron transport pathway from the electron acceptor (succinate) to the terminal donor (ubiquinone) .

Adenylylsulphate reductase A subunit (

), an iron-sulphur flavoenzyme that catalyses the reversible reduction of adenosine-5'-phosphate (APS) to sulphite and AMP .