SII-SWORD/CoKE huggingface dataset:
Tex-like domain superfamily (Tex-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain comprising amino acids 115-327 and 456-502, flanking the YqgF domain (

).

Tex (toxin expression) is a highly conserved bacterial protein involved in expression of critical toxin genes . The overall structure is notably flat and elongated. The most striking structural feature is a long, central helix comprising from amino acid residue 274 to 322. The rest of the protein wraps around the central helix at both the N-terminal and C-terminal ends. Although the Tex structure is fairly compact, it can be largely described as a series of distinct domains .
BH2638-like superfamily (BH2638-like_sf)
Type: Homologous_superfamily

This superfamily represents an orthogonal bundle domain found in proteins belonging to the uncharacterised protein family UPF0223, including protein BH2638.
Rhabdovirus nucleocapsid, N-terminal (Rhabdovirus_ncapsid_N)
Type: Homologous_superfamily

All negative-strand RNA viruses contain a ribonucleoprotein (RNP) complex that consists of the viral genome RNA completely enwrapped by the nucleoprotein (N).
The crystal structure of the N protein in complex with a single-strand RNA has been determined for two members of the rhabdovirus family, VSV and RABV . The regions in contact with RNA were mapped to a cavity formed between two structural lobes of the nucleoprotein: the N-terminal arm and the extended loop in the C-terminal lobe .

This superfamily represents the N-terminal domain.
Rhabdovirus nucleocapsid, C-terminal (Rhabdovirus_ncapsid_C)
Type: Homologous_superfamily

All negative-strand RNA viruses contain a ribonucleoprotein (RNP) complex that consists of the viral genome RNA completely enwrapped by the nucleoprotein (N).
The crystal structure of the N protein in complex with a single-strand RNA has been determined for two members of the rhabdovirus family, VSV and RABV . The regions in contact with RNA were mapped to a cavity formed between two structural lobes of the nucleoprotein: the N-terminal arm and the extended loop in the C-terminal lobe .

This superfamily represents the C-terminal domain.
Proteasome alpha-type subunit (Proteasome_alpha-type)
Type: Family

ATP-dependent protease complexes are present in all three kingdoms of life, where they rid the cell of misfolded or damaged proteins and control the level of certain regulatory proteins. They include the proteasome in Eukaryotes, Archaea, and Actinomycetales and the HslVU (ClpQY, clpXP) complex in other eubacteria. Genes homologues to eubacterial HslU (ClpY, clpX) have also been demonstrated in to be present in the genome of trypanosomatid protozoa .

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.

The prokaryotic ATP-dependent proteasome is coded for by the heat-shock locus VU (HslVU). It consists of HslV, a peptidase, and HslU (

), the ATPase and chaperone belonging to the AAA/Clp/Hsp100 family. The crystal structure of Thermotoga maritima HslV has been determined to 2.1-A resolution. The structure of the dodecameric enzyme is well conserved compared to those from Escherichia coli and Haemophilus influenzae .

This family consists of the alpha (or A type) subunits of the eukaryotic proteasome as well as some protease components of the archaeal and bacterial proteasomes.
Proteasome B-type subunit (Proteasome_suB-type)
Type: Family

ATP-dependent protease complexes are present in all three kingdoms of life, where they rid the cell of misfolded or damaged proteins and control the level of certain regulatory proteins. They include the proteasome in Eukaryotes, Archaea, and Actinomycetales and the HslVU (ClpQY, clpXP) complex in other eubacteria. Genes homologues to eubacterial HslU (ClpY, clpX) have also been demonstrated in to be present in the genome of trypanosomatid protozoa .

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.

The prokaryotic ATP-dependent proteasome is coded for by the heat-shock locus VU (HslVU). It consists of HslV, a peptidase, and HslU (

), the ATPase and chaperone belonging to the AAA/Clp/Hsp100 family. The crystal structure of Thermotoga maritima HslV has been determined to 2.1-A resolution. The structure of the dodecameric enzyme is well conserved compared to those from Escherichia coli and Haemophilus influenzae .

This family consists of the beta (or B type) subunits of the eukaryotic proteasome as well as the archaeal and bacterial proteasomes. These proteins belong to family T1 in the classification of peptidases.
REKLES domain (REKLES_domain)
Type: Domain

This entry represents the REKLES domain, found at the C-terminal of Bright/Dril1/ARID3a proteins. These proteins are B cell-specific, matrix association (or attachment) region-binding transcriptional regulator of immunoglobulin heavy chain genes and of E2F1-dependent cell cycle progression. The REKLES domain is essential for nuclear import and Crm1-dependent nuclear export of Bright . This domain is also involved in Bright multimerisation, which is necessary for DNA binding . The REKLES domain may be further subdivided into an N-terminal alpha and C-terminal beta subdomains.
ATP12 orthogonal Bundle domain superfamily (ATP12_ortho_dom_sf)
Type: Homologous_superfamily

This superfamily represents an orthogonal bundle domain found in mitochondrial ATPase F1 complex assembly protein ATP12 and homologue protein ATPAF2 (assembly factor 2) .
RAG nonamer-binding domain (RAG_nonamer-bd_dom)
Type: Domain

The variable portions of immunoglobulin and T cell receptor genes are assembled in developing lymphocytes from variable (V), joining (J), and in some cases diversity (D) gene segments, which are widely separated in the genome. These segments are brought together in a highly regulated manner by a somatic site-specific recombination reaction known as V(D)J recombination. Each gene segment is flanked by a signal sequence consisting of a conserved heptamer (consensus sequence 5'-CACAGTG-3') and nonamer (consensus sequence 5'-ACAAAAACC-3') separated by a relatively nonconserved 12 or 23 base pair (bp) spacer (12 signal or 23 signal, respectively). A segment flanked by a 12 signal can only be joined efficiently to one flanked by a 23 signal, a restriction referred to as the 12/23 rule .

The V(D)J recombinase subunits Rag-1 and Rag-2 (recombination activating gene) mediate assembly of antigen receptor gene segments. The critical step for signal recognition is binding of Rag-1 to the nonamer . The Rag-1 nonamer binding domain (NBD) forms a tightly interwoven dimer that binds and synapses two nonamer elements, with each NBD making contact with both DNA molecules. Each NBD monomer is composed of three helices: H1, H2 and H3. Helix 1 contains a kink that separates it into two smaller helices: H1a and H1b. Helices H2 and H3 from each subunit form a four-helix bundle through extensive hydrophobic interactions and constitute the bulk of the dimer interface, whereas the H1 helices from the two subunits wrap around one side of the four-helix bundle with the N-terminal GGRPR motifs protruding from opposite sides of the dimer. The GGRPR motif is an example of an AT-hook, a structural element found in various DNA binding proteins .
c-Kit-binding domain (KBD)
Type: Domain

This entry represents the c-Kit binding domain found in metazoan Spread (Sprouty-related, EVH1 domain-containing) proteins. This domain has been shown to be necessary for Spread-1 phosphorylation and is not similar to other previously reported tyrosine kinase interacting domains, such as SH2 or c-Met binding domains .

Despite being matched by this signature, Spread-3 family members contain inactive c-Kit binding domains as an arginine residue essential for c-Kit binding is mutated to glycine .
Arterivirus NSP4 peptidase domain (Arterivirus_NSP4_peptidase)
Type: Domain

Ths entry represents the NSP4 proteinase of arteriviruses.

Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries:

Equine arteritis virus (EAV).

Porcine reproductive and respiratory syndrome virus (PRRSV).

Mice actate dehydrogenase-elevating virus.

Simian hemorrhagic fever virus.

The arterivirus replicase gene encodes two large precursor polyproteins that are processed by the viral main proteinase nonstructural protein 4 (NSP4). The structure of the enzyme reveals two chymotrypsin-like antiparallel β-barrels and an extra C-terminal α/β domain that may play a role in mediating protein-protein interactions. The N-terminal barrel consists of six β-strands (A1 to F1), while the C-terminal barrel is composed of seven (A2 to G2). The core of both β-barrels is comprised of conserved hydrophobic residues. The additional C-terminal domain consists of two pairs of short antiparallel β-sheets and two α-helices. It interacts with the C-terminal barrel through an interface consisting of conserved hydrophobic residues. A canonical catalytic triad that is composed of Ser, His, and Asp is located in the open cleft between the β-barrels domain . The nsp4 proteinase domain is a member of peptidase family S32.
CVC domain (CVC)
Type: Domain

This entry represents the CVC (Chx10/Vsx-1 and ceh-10) domain, which is found in visual system homeobox proteins. Homeobox-containing genes encode transcription factors and are characterised by the homeodomain (HD), a motif that directs specific DNA binding to regulate the expression of target genes. Homeobox genes are grouped into several subclasses according to the primary structure of their HD and its flanking sequences. Among the paired-like subclass, the paired-like CVC (PLC)-homeodomain proteins (HDPs) are characterised by a conserved CVC domain and can be grouped into the Vsx-1 and Vsx-2 family, containing orthologs from several species. The characteristic feature of the Vsx-1 group are the existence of a RV domain and LG sequence and the lack of a Paired-Tail/OAR domain. Instead of an RV domain, the Vsx-2 group proteins have a conserved 14 amino acid motif called the Paired-Tail or OAR domain. These specific domain differences may correlate with the functional specificity of each group. PLC-HDPs appear to play a particular role in occular development and execute their functions by binding to the conserved locus control region (LCR), located upstream of the transcrption initiation site of the red opsin gene, and thus specify the development and differenciation of cone photoreceptors and a subset of retinal inner nuclear layer bipolar cells.
UMA domain (UMA)
Type: Domain

A key aspect of eukaryotic intracellular trafficking is the sorting of cell-surface proteins into multi-vesicular endosomes or bodies (MVBs), which eventually fuse with the lysosome, where they are degraded by lipases and peptidases. This is the primary mechanism for down-regulation of signaling via transmembrane receptors and removal of misfolded or defective membrane proteins. This process is also utilised by several viruses (e.g. HIV-1) to facilitate budding of their virions from the cell-membrane. Studies in animals and fungi have shown that it depends on an intricate series of interactions, which is initiated via ubiquitination (typically one or more mono-ubiquitinations) of the cytoplasmic tails of membrane proteins by specific E3 ligases. Ubiquitinated membrane proteins are then captured into endosomes by the ESCRT system and prevented from being recycled back to the plasma membrane via the retrograde trafficking system. The ESCRT system also folds the endosomal membranes into invaginations that are concentrated in these ubiquitinated targets and catalyzes their abscission into intra-luminal-vesicles inside the endosome. This largely seals the fate of these membrane proteins as targets for lysosomal degradation. The ESCRT system is comprised of 4 major protein complexes, ESCRT-0 to ESCRT-III, which are successively involved in the above-described steps .

ESCRT-I contains three subunits that are conserved between yeast and animals, namely the inactive E2-ligase protein TSG101/VPS23, VPS28 and VPS37. Additionally, both yeast and metazoan ESCRT-I contain a fourth subunit termed MVB12 (multivesicular body sorting factor of 12 kD); however, the MVB12 subunits from the two lineages do not show significant sequence similarity. The metazoan MVB12 proteins contain two distinct conserved domains that occur independently in various proteins. The C-terminal region of MVB12, which is shared with ubiquitin associated protein-1 (UBAP1), forms the UBAP1-MVB12 associated (UMA) domain. Human UBAP1 is implicated in nasopharyngeal carcinoma risk and fronto-temporal lobar degeneration. The UMA domain is also found in several other poorly characterised proteins, including at leat one orthologous group of proteins conserved in vertebrates prototyped be the human protein LOC390595 and another group conserved across Metazoa typified by human tcag7.903. The UMA domain found in MVB12 and UBAP1 defines a novel adaptor that might recruit diverse targets to ESCRT-I. The different UMA proteins might function as alternative as MVB12-like subunit that recruit different targets via their specific intercation modules (such as MABP) or UBA or the specific extensions) to the ESCRT-I complex .

This entry represents the UMA domain, which contains a conserved proline followed by a hydrophobic residue in the N terminus and a nearly absolutely conserved glutamate at the C terminus. It is predicted to adopt an α+β fold .
APO domain (APO_dom)
Type: Domain

This entry represents the APO domain which is found in plant APO (Accumulation of photosystem) proteins. The domain contains conserved cysteine and histidine residues . It functions as an RNA-binding domain .
Penicillin amidase type, domain 1 (Penicillin_amidase_dom1)
Type: Homologous_superfamily

Penicillin amidase or penicillin acylase catalyses the hydrolysis of benzylpenicillin to phenylacetic acid and 6-aminopenicillanic acid (6-APA) a key intermediate in the the synthesis of penicillins .

This superfamily represents the N-terminal structural domain of the penicillin amidase peptidases. It forms an α-helical orthogonal bundle . This domain is also found in other S45 peptidases like Glutaryl-7-aminocephalosporanic-acid acylase.
Lysozyme-like domain superfamily (Lysozyme-like_dom_sf)
Type: Homologous_superfamily

This entry represents a lysozyme-like domain superfamily found in glycosyl hydrolases and transglycosylases.
Lysozyme domain superfamily (Lysozyme_dom_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily found in phage lysozyme and related proteins , including Bacteriophage lambda lysozyme and Escherichia coli endolysin . Lysozyme helps to release mature phage particles from the cell wall by breaking down the peptidoglycan. The enzyme hydrolyses the 1,4-beta linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of prokaryotic cell walls. E. coli endolysin also functions in bacterial cell lysis and acts as a transglycosylase. The Bacteriophage T4 lysozyme structure contains two domains, the interface between which forms the active-site cleft. The N terminus of the two domains undergoes a 'hinge-bending' motion about an axis passing through the molecular waist . This mobility is thought to be important in allowing access of substrates to the enzyme active site.
Ammonia monooxygenase/particulate methane monooxygenase, subunit C domain superfamily (NH3_CH4_mOase_C_sf)
Type: Homologous_superfamily

Ammonia monooxygenase and the particulate methane monooxygenase are both integral membrane proteins, occurring in ammonia oxidisers and methanotrophs respectively, which are thought to be evolutionarily related . These enzymes have a relatively wide substrate specificity and can catalyse the oxidation of a range of substrates including ammonia, methane, halogenated hydrocarbons and aromatic molecules . These enzymes are composed of 3 subunits - A (

), B (

,

) and C (

) - and contain various metal centres, including copper. Particulate methane monooxygenase from Methylococcus capsulatus str. Bath is an ABC homotrimer, which contains mononuclear and dinuclear copper metal centres, and a third metal centre containing a metal ion whose identity in vivo is not certain.

The C subunit from Methylococcus capsulatus str. Bath resides primarily in the membrane and consists of five transmembrane helices. Several conserved residues contribute to a metal binding centre .

This superfamily represents the structural domain of the C subunit of ammonia monooxygenase/particulate methane monooxygenase.
YppE-like superfamily (YppE-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain which consists of a four α-helical up-and-down bundle. It is found in a family of uncharacterised proteins .
Membrane associated eicosanoid/glutathione metabolism-like domain superfamily (MAPEG-like_dom_sf)
Type: Homologous_superfamily

This domain is found in a widespread superfamily known as MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) . Included in this superfamily are:

5-lipoxygenase activating protein (gene FLAP), which seems to be required for the activation of 5-lipoxygenase.

Leukotriene C4 synthase (

), which catalyses the production of LTC4 from LTA4.

Microsomal glutathione S-transferase II (

) (GST-II), which also produces LTC4 from LTA4.

Prostaglandin E synthase, which catalyses the synthesis of PGE2 from PGH2 (produced by cyclooxygenase from arachidonic acid).

The structure of this domain consists of four transmembrane helices .
LemA-like domain superfamily (LemA-like_dom_sf)
Type: Homologous_superfamily

The exact molecular function of the LemA protein

is uncertain.

Structurally LemA consists of a four-helical bundle where helices 2 and 3 are shorter than helices 1 and 4. It is predicted to be a transmembrane protein with an extracellular N terminus .
Myotoxin/Anemone neurotoxin domain superfamily (Myo_ane_neurotoxin_sf)
Type: Homologous_superfamily

This superfamily represents the β-sheet domain found in snake myotoxin and anemone neurotoxins .
Leucyl-tRNA synthetase, domain 3 (Leu-tRNA-synth_dom3)
Type: Domain

Leucine-tRNA ligase (

) is an alpha monomer that belongs to class Ia. The crystal structure of leucine-tRNA ligase from the hyperthermophile Thermus thermophilus has an overall architecture that is similar to that of isoleucine-tRNA ligase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote-like leucine-tRNA ligases, as is the presence of a novel additional flexibly inserted domain . This entry represents the small inserted domain, found in leucyl-tRNA synthetases from Thermaceae bacteria. It is flexibly linked to the enzyme-core by β-ribbons structures .
Peptidase M18, domain 2 (Peptidase_M18_dom2)
Type: Homologous_superfamily

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to the MEROPS peptidase family M18, (clan MH). The proteins have two catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu and His. The catalysed reaction involves the release of an N-terminal aminoacid, usually neutral or hydrophobic, from a polypeptide .

The type example is aminopeptidase I from Saccharomyces cerevisiae (Baker's yeast), the sequence of which has been deduced, and the mature protein shown to consist of 469 amino acids . A 45-residue presequence contains both positively- and negatively-charged and hydrophobic residues, which could be arranged in an N-terminal amphiphilic α-helix . The presequence differs from signal sequences that direct proteins across bacterial plasma membranes and endoplasmic reticulum or into mitochondria. It is unclear how this unique presequence targets aminopeptidase I to yeast vacuoles, and how this sorting utilises classical protein secretory pathways .

This entry represents the β roll structural domain found in M18 family and aspartyl aminopeptidases.
Dihydroorotate dehydrogenase A, chain A, domain 2 (Dihydro_DH_chainA_dom2)
Type: Homologous_superfamily

Dihydroorotate dehydrogenase (

) (DHOdehase) catalyses the fourth step in the
de novo
biosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is located on the inner side of the cytosolic membrane. In some yeasts, such as in
Saccharomyces cerevisiae (gene URA1, subfamily 2), it is a cytosolic protein while in other eukaryotes it is found in the mitochondria .

This superfamily represents the structural domain 2 which forms a β roll.
DUF1285, beta-roll domain superfamily (DUF1285_beta_roll_sf)
Type: Homologous_superfamily

This structural β-roll domain is found towards the C terminus of the bacterial protein family with no known function, DUF1285.