SII-SWORD/CoKE huggingface dataset:
Cytochrome c oxidase, subunit Va/VI superfamily (Cyt_c_oxidase_su5A/6_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex are encoded within the mitochondrial genome, there are a variable number of small polypeptidic subunits encoded within the nuclear genome. This entry represents subunits Va and VI, which are the heme A-containing chains of cytochrome c oxidase. Subunit Va is one of three mammalian subunits that lacks a transmembrane region. Subunit Va is located on the matrix side of the membrane and binds thyroid hormone T2, releasing allosteric inhibition caused by the binding of ATP to subunit IV and allowing high turnover at elevated intramitochondrial ATP/ADP ratios .
Mediator complex subunit 15, KIX domain (MED15_KIX)
Type: Domain

GAL11 is a component of the Mediator complex, a co-activator that plays critical roles in transcriptional activation. The GAL11/MED15 subunit has an N-terminal KIX domain, which is an activator-binding domain. This domain contains a docking site for the activation domain of yeast drug resistance protein Pdr1, therefore is thought to be involved in antifungal/xenobiotic-dependent regulation of multidrug resistance .
Cytochrome c oxidase, subunit 8 superfamily (Cyt_c_oxidase_su8_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In fungi (as in other eukaryotes) this enzyme complex is located in the mitochondrial inner membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptide subunits. This family includes fungal-type cytochrome-c oxidase, subunit VIIa, also known as cytochrome c oxidase subunit 8 .
Cytochrome c oxidase subunit 6B/Cytochrome c oxidase assembly factor 6-like superfamily (CX6/COA6-like_sf)
Type: Homologous_superfamily

This superfamily includes the cytochrome c oxidase subunit 6B (CX6), Cytochrome c oxidase assembly factor 6 (COA6) and their respective homologues.

Cytochrome c oxidase (

) is an oligomeric enzymatic complex that is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptide subunits. One of these subunits is the potentially haem-binding subunit, VIb, which is encoded in the nucleus . Subunit VIb is one of three mammalian subunits that lacks a transmembrane region. It is located on the cytosolic side of the membrane and helps form the dimer interface with the corresponding subunit on the other monomer complex .
Peridinin-chlorophyll A binding superfamily (Peridinin-chlorophyll-bd_sf)
Type: Homologous_superfamily

Peridinin-chlorophyll-protein, a water-soluble light-harvesting complex that has a blue-green absorbing carotenoid as its main pigment, is present in most photosynthetic dinoflagellates. These proteins are composed of two similar repeated domains. These domains constitute a scaffold with pseudo-twofold symmetry surrounding a hydrophobic cavity filled by two lipid, eight peridinin, and two chlorophyll a molecules . They have a multihelical fold which forms a boat-shaped protein shell around cofactors.
Flavin prenyltransferase-like (Flavin_trans-like)
Type: Homologous_superfamily

This entry contains a diverse range of flavoprotein enzymes, including epidermin decarboxylase, EpiD, which has been shown to be a flavoprotein that binds FMN . This enzyme catalyses the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond.

This superfamily also includes the B-chain of dipicolinate synthase. Dipicolinate synthase catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid. Dipicolinic acid is a small polar molecule that accumulates to high concentrations in bacterial endospores and is thought to play a role in spore heat resistance, or the maintenance of heat resistance . This superfamily also includes phenolic acid decarboxylase (also known as phenylacrylic acid decarboxylase [ec:4.1.1.-]) .
Core-binding factor, beta subunit superfamily (CBF_bsu_sf)
Type: Homologous_superfamily

Core binding factor (CBF) is a heterodimeric transcription factor essential for genetic regulation of hematopoiesis and osteogenesis. The beta subunit binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including Murine leukemia virus, Polyomavirus enhancer, T-cell receptor enhancers etc. The beta subunit enhances DNA-binding ability of the alpha subunit
in vitro
, and has been show to have a structure related to the OB fold . This superfamily also includes the Drosophila melanogaster brother and big brother proteins, which regulate the DNA-binding properties of Runt.

The CBF structure has a close barrel fold with meander and is capped at both ends by α-helices.
RNA 3'-terminal phosphate cyclase, insert domain superfamily (RPTC_insert)
Type: Homologous_superfamily

RNA cyclases are a family of RNA-modifying enzymes that are conserved in eukaryotes, bacteria and archaea. RNA 3'-terminal phosphate cyclase (

) catalyses the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA.

ATP + RNA 3'-terminal-phosphate = AMP + diphosphate + RNA terminal-2',3'-cyclic-phosphate

These enzymes might be responsible for production of the cyclic phosphate RNA ends that are known to be required by many RNA ligases in both prokaryotes and eukaryotes.

RNA cyclase is a protein of from 36 to 42kDa. The best conserved region is a glycine-rich stretch of residues located in the central part of the sequence and which is reminiscent of various ATP, GTP or AMP glycine-rich loops.

The crystal structure of RNA 3'-terminal phosphate cyclase shows that each molecule consists of two domains. The larger domain contains three repeats of a folding unit comprising two parallel α helices and a four-stranded β sheet; this fold was previously identified in translation initiation factor 3 (IF3). The large domain is similar to one of the two domains of 5-enolpyruvylshikimate-3-phosphate synthase and UDP-N-acetylglucosamine enolpyruvyl transferase. The smaller insert domain disrupts the large domain, and uses a similar secondary structure element with different topology, observed in many other proteins such as thioredoxin . Although the active site of this enzyme could not be unambiguously assigned, it can be mapped to a region surrounding His309, an adenylate acceptor, in which a number of amino acids are highly conserved in the enzyme from different sources .

This superfamily represents the small insert domain that interrupts the large repetitive domain.
GHMP kinase, C-terminal domain superfamily (GHMP_kinase_C_sf)
Type: Homologous_superfamily

This domain superfamily is found in homoserine kinases (

), galactokinases (

) and mevalonate kinases (

). These kinases make up the GHMP kinase superfamily of ATP-dependent enzymes . These enzymes are involved in the biosynthesis of isoprenes and amino acids as well as in carbohydrate metabolism. The C-terminal domain of homoserine kinase has a central α-β plait fold and an insertion of four helices, which, together with the N-terminal fold, create a novel nucleotide binding fold .

This domain superfamily is also found in some diphosphomevalonate decarboxylases, which are structurally related members of the GHMP superfamily , but do not possess kinase activity.
NusA, N-terminal domain superfamily (NusA_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal RNA polymerase-binding domain of bacterial transcription factors such as NusA (N-utilising substance A). NusA is involved in transcriptional pausing, termination and anti-termination. NusA from Thermotoga maritima contains an N-terminal domain and three RNA-binding domains (one S1 domain and two KH domains). The N-terminal domain consists of a bifurcated coiled β-sheet within an α/β(3)/α/β/α fold, which can be divided into two subdomains: a globular head and a helical body. The globular head subdomain may interact with RNA polymerase, while the helical body displays a similar structure to that of the helical domain in sigma70 .
Protein-arginine deiminase, central domain superfamily (PAD_central_sf)
Type: Homologous_superfamily

Peptidylarginine deiminase (PAD) enzymes catalyse the conversion of protein-bound arginine to citrulline. There are five types of PADs known in humans, PAD1-PAD4 and PAD6 . PAD6 does not bind Ca2+ and is inactive in vitro assays against standard PADs substrate . This entry represents the central non-catalytic domain of protein-arginine deiminase. This domain has an immunoglobulin-like fold .
Methanol dehydrogenase, beta subunit superfamily (Meth_DH_bsu_sf)
Type: Homologous_superfamily

Methanol dehydrogenase (MDH) (

), found in Gram-negative bacteria, is a pyrroloquinoline quinone (PQQ)-containing enzyme which oxidises methanol to formaldehyde. It is located in the periplasmic space and passes electrons derived from the oxidation of methanol to the soluble cytochrome cL . The enzyme is a tetramer composed of two large alpha subunits and two smaller beta subunits. The alpha subunit binds the PQQ cofactor and contains the active site, while the function of the beta subunit is currently unknown . The alpha subunit forms an eight-bladed propeller structure, with several novel tryptophan-docking motifs linking the individual blades together.

This entry represents the beta subunit of methanol dehydrogenase. Its structure consists of a single α-helix and an irregular N-terminal tail.
YqbG-like superfamily (YqbG-like_sf)
Type: Homologous_superfamily

YqbG, an uncharacterised protein from Bacillus, is the representative of this superfamily. YqbG exists as a monomer, consisting of four α-helices with a right-handed twist, arranged in a left-handed superhelix .
Bacteriochlorophyll A superfamily (Chl_A_sf)
Type: Homologous_superfamily

Bacteriochlorophyll A (or FMO) protein is involved in the energy transfer system of photosynthetic bacteria, such as Green Sulphur Bacteria. Bacteriochlorophyll A acts as a light-harvesting complex that directs light energy from the chlorosomes attached to the cell membrane to the reaction centre . The protein forms a homotrimer, with each monomer unit containing seven molecules of bacteriochlorophyll A.
Methylamine/Aralkylamine dehydrogenase light chain superfamily (MADH/AADH_L_sf)
Type: Homologous_superfamily

Aralkylamine dehydrogenase light chain and methylamine dehydrogenase light chain are aromatic amine dehydrogenases that form heterotetramers with their respective heavy chains, and catalyse the oxidative deamination of amines to their corresponding aldehydes.

The light subunit possesses an apparent Tat signal peptide. This subunit is dominated by β structure .
Mitochondrial glycoprotein superfamily (MAM33_sf)
Type: Homologous_superfamily

This mitochondrial matrix protein superfamily contains members of the MAM33 superfamily which bind to the globular 'heads' of C1Q.b. It is thought to be involved in mitochondrial oxidative phosphorylation and in nucleus-mitochondrion interactions . Its structure consists of an β(7)-α(2) fold with N- and C-terminal extensions forming a coiled coil subdomain.
Baculovirus p35 superfamily (Baculovirus_p35_sf)
Type: Homologous_superfamily

The anti-apoptotic protein p35 from baculovirus is thought to prevent the suicidal response of infected insect cells by inhibiting caspases. Ectopic expression of p35 in a number of transgenic animals or cell lines is also anti-apoptotic, giving rise to the hypothesis that the protein is a general inhibitor of caspases.

The baculovirus p35 structure forms a sandwich composed of 14 strands in 2 sheets with a greek-key topology.
Molybdopterin biosynthesis MoaE subunit superfamily (MoaE_sf)
Type: Homologous_superfamily

Members of the MoaE family are involved in biosynthesis of the molybdenum cofactor (Moco), an essential cofactor for a diverse group of redox enzymes. Moco biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes. Moco contains a tricyclic pyranopterin, termed molybdopterin (MPT), which carries the cis-dithiolene group responsible for molybdenum ligation. This dithiolene group is generated by MPT synthase in the second major step in Moco biosynthesis. MPT synthase is a heterotetramer consisting of two large (MoaE) and two small (MoaD) subunits .

Structurally, the MoaE subunit has a β-β-α-β-β-β-α fold and contains a β-hammerhead motif similar to that in barrel-sandwich hybrids.
AF0941-like superfamily (AF0941-like_sf)
Type: Homologous_superfamily

This entry represents the hypothetical protein AF_0941 from the hyperthermophilic sulphate-reducing archaeon Archaeoglobus fulgidus. The structure of this protein consists of several α-helices arranged in an orthogonal bundle.
Mur-like, catalytic domain superfamily (Mur-like_cat_sf)
Type: Homologous_superfamily

Mur ligases play an essential role in the intracellular biosynthesis of bacterial peptidoglycan. Mur ligases share the same three-domain topology, with N-terminal and central domains responsible for binding the UDP-precursor and ATP, respectively, while the C-terminal part binds the condensing amino acid residue .

This superfamily represents the central domain from all four Mur enzymes: UDP-N-acetylmuramate-L-alanine ligase (MurC), UDP-N-acetylmuramoylalanine-D-glutamate ligase (MurD), UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase (MurE), and UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF). It also includes folylpolyglutamate synthase that transfers glutamate to folylpolyglutamate and cyanophycin synthetase that catalyses the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin) .
Pyrimidine nucleoside phosphorylase-like, C-terminal domain superfamily (PYNP-like_C_sf)
Type: Homologous_superfamily

This domain superfamily is found at the C-terminal end of the large α/β domain making up various pyrimidine nucleoside phosphorylases . It has slightly different conformations in different members of this family. For example, in pyrimidine nucleoside phosphorylase (PYNP,

) there is an added three-stranded antiparallel β sheet as compared to other members of the family, such as Escherichia coli thymidine phosphorylase (TP,

) . The domain contains an α/β hammerhead fold and residues in this domain seem to be important in formation of the homodimer .
Ribosome hibernation promotion factor-like (RHF-like)
Type: Homologous_superfamily

This superfamily consists of ribosome hibernation promoting factors (RHFs). RHF promotes and stabilizes dimerization of 70S ribosomes by the ribosome modulation factor (RMF), leading to the formation of inactive 100S ribosomes during the stationary phase .
Gamma-glutamyl cyclotransferase-like superfamily (GGCT-like_sf)
Type: Homologous_superfamily

Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is encoded by the gene C7orf24 . The enzyme participates in the gamma-glutamyl cycle, which plays a pre-eminent role in glutathione homoeostasis . The synthesis and metabolism of glutathione (L-gamma-glutamyl-L-cysteinylglycine) ties the gamma-glutamyl cycle to numerous cellular processes; glutathione acts as a ubiquitous reducing agent in reductive mechanisms involved in protein and DNA synthesis, transport processes, enzyme activity, and metabolism.

Structurally, GGCT is comprised of 7 β strands and 2 α helices, and it folds into a five-stranded, antiparallel β-barrel .
Sugar-phosphate isomerase, RpiB/LacA/LacB superfamily (RpiB_LacA_LacB_sf)
Type: Homologous_superfamily

This entry represents the sugar isomerase enzymes ribose 5-phosphate isomerase B (RpiB), galactose isomerase subunit A (LacA) and galactose isomerase subunit B (LacB).

Galactose-6-phosphate isomerase (

) is a heteromultimeric protein consisting of subunits LacA and LacB, and catalyses the conversion of D-galactose 6-phosphate to D-tagatose and 6-phosphate in the tagatose 6-phosphate pathway of lactose catabolism . Galactose-6-phosphate isomerase is induced by galactose or lactose.

Ribose 5-phosphate isomerase (

) forms a homodimer and catalyses the interconversion of D-ribose 5-phosphate and D-ribulose 5-phosphate in the non-oxidative branch of the pentose phosphate pathway. This reaction permits the synthesis of ribose from other sugars, as well as the recycling of sugars from nucleotide breakdown. Two unrelated enzymes can catalyse this reaction: RpiA (found in most organisms) and RpiB (found in some bacteria and eukaryotes). RpiB is also involved in metabolism of the rare sugar, allose, in addition to ribose sugars. The structures of RpiA and RpiB are distinct, RpiB having a Rossmann-type α/β/α sandwich topology .
HORMA domain superfamily (HORMA_dom_sf)
Type: Homologous_superfamily

The HORMA domain (for HOP1, REV7 and MAD2) is an about 180-240 amino acids region containing several conserved motifs. Whereas the MAD2 and the REV7 proteins are almost entirely made up of HORMA domains, HOP1 contains a HORMA domain in its N-terminal region and a Zn-finger domain, whose general arrangement of metal-chelating residues is similar to that of the PHD finger, in the C-terminal region. The HORMA domain is found in proteins showing a direct association with chromatin of all crown group eukaryotes. It has been suggested that the HORMA domain recognises chromatin states that result from DNA adducts, double-stranded breaks or non-attachment to the spindle and acts as an adaptor that recruits other proteins involved in repair .

Secondary structure prediction suggests that the HORMA domain is globular and could potentially form a complex β-sheet(s) with associated α-helices .

Some proteins known to contain a HORMA domain are listed below:

Eukaryotic HOP1, a conserved protein that is involved in meiotic-synaptonemal-complex assembly.

Eukaryotic mitotic-arrest-deficient 2 protein (MAD2), a key component of the mitotic-spindle-assembly checkpoint .

Eukaryotic REV7, a subunit of the DNA polymerase zeta that is involved in translesion, template-independent DNA synthesis.

Fungal Atg13, adaptor protein for the Atg1 kinase complex .
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase superfamily (MECDP_synthase_sf)
Type: Homologous_superfamily

IspF is a MECDP (2-C-methyl-D-erythritol 2,4-cyclodiphosphate) synthetase, also known as YgbB. It is an enzyme in the non-mevalonate pathway of isoprenoid synthesis. Isoprenoids are essential in all organisms, and can also be synthesized through the mevalonate pathway. The non-mevolante route is used by many bacteria and human pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum. This route appears to involve seven enzymes. MECDP synthetase catalyses the intramolecular attack by a phosphate group on a diphosphate, with cytidine monophosphate (CMP) acting as the leaving group to give the cyclic diphosphate product MEDCP. The enzyme is a trimer with three active sites shared between adjacent copies of the protein. The enzyme also has two metal binding sites, the metals playing key roles in catalysis.

A number of proteins from eukaryotes and prokaryotes are bifunctional proteins with an N-terminal IspD domain and a C-terminal IspF domain .

Structurally, IpsF forms trimers with three closely packed β-sheets.
Doublecortin domain superfamily (Doublecortin_dom_sf)
Type: Homologous_superfamily

X-linked lissencephaly is a severe brain malformation affecting males. Recently it has been demonstrated that the doublecortin gene is implicated in this disorder . Doublecortin was found to bind to the microtubule cytoskeleton. In vivo and in vitro assays show that Doublecortin stabilises microtubules and causes bundling . Doublecortin is a basic protein with an iso-electric point of 10, typical of microtubule-binding proteins. However, its sequence contains no known microtubule-binding domain(s).

The detailed sequence analysis of Doublecortin and Doublecortin-like proteins allowed the identification of an evolutionarily conserved Doublecortin (DC) domain, which is ubiquitin-like. This domain is found in the N terminus of proteins and consists of one or two tandemly repeated copies of an around 80 amino acids region. It has been suggested that the first DC domain of Doublecortin binds tubulin and enhances microtubule polymerisation .

Some proteins known to contain a DC domain are listed below:

Doublecortin. It is required for neuronal migration . A large number of point mutations in the human DCX gene leading to lissencephaly are located within the DC domains .

Human serine/threonine-protein kinase DCAMKL1. It is a probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain .

Retinitis pigmentosa 1 protein. It is required for the differentiation of photoreceptor cells. Mutation in the human RP1 gene cause retinitis pigmentosa of type 1 .
Carbohydrate-binding module superfamily 5/12 (CBM_sf_5/12)
Type: Homologous_superfamily

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose . However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see .

This entry represents

and

. These modules have a core structure consisting of a 3-stranded meander β-sheet, which contain six aromatic groups that may be important for binding. CBM5/12 is found in proteins such as chitinase A1, chitinase B , and endoglucanase Z .

The overall topology of the CBM is structurally similar to the C-terminal chitin-binding domains (ChBD) of chitinase A1 and chitinase B, however the binding mechanism for the ChBD may be different from that of the CBM .