SII-SWORD/CoKE huggingface dataset:
Signal peptide peptidase A (S49_SppA_1)
Type: Domain

This entry contains signal peptide peptidase A (SppA; protease IV; MEROPS identifier S49.001). SppA is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Site-directed mutagenesis and sequence analysis have shown SppA to be a serine protease. The predicted active site serine for members in this family occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic centre comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in many serine proteases . In addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members, the E. coli SppA contains an amino-terminal domain, similar to Arabidopsis thaliana SppA1 peptidase. Others, including sohB peptidase, protein C and archaeal signal peptide peptidase, do not contain the amino-terminal domain. Unusually, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the conserved carboxy-terminal protease domain and the lysine in the non-conserved amino-terminal domain .
Bacteriophage protein C (Protein_C)
Type: Domain

Peptidase family S49 includes signal peptide peptidases (SppAs). Site-directed mutagenesis and sequence analysis have shown these SppAs to be serine proteases. The predicted active site serine for members in this family occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic centre comprises a Ser-Lys dyad and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases .

Protein C from bacteriophage lambda (MEROPS identifier S49.003) is the peptidase responsible for the processing of several viral proteins. It activates itself, degrades the internal scaffold protein upon which the procapsid is assembled, and processes the portal complex protein gpB . This entry also includes the scaffold protein from bacteriophage P21 and proteins from bacteria which are presumably the result of integration of viral DNA.
Flavin-dependent tryptophan halogenase (Trp_halogen)
Type: Family

Flavin-dependent tryptophan halogenase PrnA catalyses the chlorination of tryptophan to form 7-chlorotryptophan . This is the first step in the biosynthesis of pyrrolnitrin, an antibiotic with broad-spectrum antifungal activity produced by a number of Pseudomonas and Burkholderia strains and a few other soil bacteria . The flavin-dependent tryptophan halogenase RebH from Lentzea aerocolonigenes is involved in the biosynthesis of the indolocarbazole antitumor agent rebeccamycin .
Bacillopeptidase F, peptidase domain (Bacillopeptidase_F)
Type: Domain

Bacillus subtilis produces and secretes proteases and other types of exoenzymes at the end of the exponential phase of growth . The ones that make up this group are known as bacillopeptidase F (MEROPS identifier S08.017), encoded by bpr, a serine protease with high esterolytic activity which is inhibited by PMSF . Bacillopeptidase F is fibrinolytic and is synthesized as a precursor, which is either activated autocatalytically or by another, unidentified B. subtilis peptidase . Like other members of the peptidases S8 family these have a Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity .

These proteins contain a domain found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin) and S53 (sedolisin), both of which are members of clan SB .

The subtilisin family is one of the largest serine peptidase families characterised to date. Over 200 subtilises are presently known, more than 170 of which with their complete amino acid sequence . It is widespread, being found in eubacteria, archaebacteria, eukaryotes and viruses . The vast majority of the family are endopeptidases, although there is an exopeptidase, tripeptidyl peptidase . Structures have been determined for several members of the subtilisin family: they exploit the same catalytic triad as the chymotrypsins, although the residues occur in a different order (HDS in chymotrypsin and DHS in subtilisin), but the structures show no other similarity . Some subtilisins are mosaic proteins, while others contain N- and C-terminal extensions that show no sequence similarity to any other known protein .

The proprotein-processing endopeptidases kexin, furin and related enzymes form a distinct subfamily known as the kexin subfamily (S8B). These preferentially cleave C-terminally to paired basic amino acids. Members of this subfamily can be identified by subtly different motifs around the active site . Members of the kexin subfamily, along with endopeptidases R, T and K from the yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require thiol activation. This can be attributed to the presence of a cysteine near to the active site histidine . Only one viral member of the subtilisin family is known, a 56kDa protease from herpes virus 1, which infects the channel catfish .
26S Proteasome non-ATPase regulatory subunit 7/8 (MPN_RPN7_8)
Type: Family

This entry includes lid subunits of the 26 S proteasome regulatory particles, Rpn7 (PSMD7; proteasome 26S non-ATPase subunit 7; p44), and Rpn8 (PSMD8; proteasome 26S non-ATPase subunit 8; p40; Mov34). Rpn7 is known to be critical for the integrity of the 26 S proteasome complex by establishing a correct lid structure . It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. Rpn7 and Rpn8 are ATP-independent components of the 19S regulator subunit, and contain the MPN structural motif on its N-terminal region. However, while they show a typical MPN metalloprotease fold and are members of peptidase family M67, they lack the canonical JAMM motif, and therefore do not show catalytic isopeptidase activity . Rpn7 is considered a non-peptidase homologue (MEROPS identifier M67.973). It is suggested that Rpn7 function is primarily structural .
COP9 signalosome subunit 6 (MPN_CSN6)
Type: Family

The COP9 signalosome (CSN) is a conserved protein complex that regulates the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes , which leads to a decrease in Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 . Protein kinases CK2 and D, which phosphorylate proteins such as cJun and p53 resulting in their degradation by the ubiquitin-26S proteasome system, also binds to CSN . The mammalian CSN typically consistis of eight subunits designated CSN1-CSN8. The fission yeast possesses a smaller version of the CSN, consisting only of six subunits, whereas a more distant CSN-like complex has been described in Saccharomyces cerevisiae .

CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD; MEROPS identifier M67.972) is one of the eight subunits of COP9 signalosome. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5 . It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6 . CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells . The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.
Brcc36 isopeptidase (MPN_BRCC36)
Type: Family

BRCC36 (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36; MEROPS identifier M67.004) and BRCC36-like proteins are JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn
2+
-dependent ubiquitin isopeptidase activity. BRCC36 specifically cleaves Lys 63-linked polyubiquitin chains .

BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity . It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs . BRCC36 exists in at least two distinct complexes, the RAP80 complex (also called the BRCA1-A complex) and the BRCC36 isopeptidase complex (BRISC) .
Putative metalloprotease, Jacalin-like lectin domain (Jacalin-like_metallopeptidase)
Type: Domain

Domains in this group, which appears restricted to fungi, co-occur with protein domains that contain an HExxH motif characteristic of metallopeptidases. They have not been functionally characterised.
Scytalidoglutamic peptidase (Scytalidoglutamic_peptidase)
Type: Family

This entry includes scytlidoglutamic peptidase (MEROPS identifier G01.001). The enzyme is active at acidic pH but is not inhibited by pepstatin, which led to it being considered a pepstatin-insensitive aspartic peptidase . It was shown from the crystal structure that the active site residues are a glutamate (E) and glutamine (Q) , and the name "eqolysin" was proposed for this family .
Deubiquitinating enzyme 14, UBA domain (UBA2_scUBP14-like)
Type: Domain

scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14 (MEROPS identifier C19.083), is the Saccharomyces cerevisiae orthologue of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast . Members in this family contain two tandem ubiquitin-association (UBA) domains.

This entry corresponds to the UBA2 domain in Saccharomyces cerevisiae UBP14 and related proteins .
Plasmepsin 5 (Plasmepsin_5)
Type: Domain

The entry contains a group of aspartic proteinases homologous to plasmepsin 5 (MEROPS identifier A01.075). Plasmepsins are a class of at least 10 enzymes produced by the Plasmodium parasite. Because some plasmepsins degrade haemoglobin, they are an important cause of symptoms in malaria sufferers. This family of enzymes is a potential target for anti-malarial drugs. There are several types of plasmepsins, closely related but varying in the specificity of cleavage site. The name plasmepsin may come from plasmodium (the organism) and pepsin (a common aspartic acid protease with similar molecular structure). This group of aspartate endopeptidases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

Proteins exported by Plasmodium to its host erythrocyte contain a signal peptide followed by a transit PEXEL motif (Arg-Xaa-Leu-Xaa-Glu/Gln/Asp). Plasmepsin 5 removes the PEXEL motif . Cleavage occurs at the leucyl bond . Some proteins lacking the canonical PEXEL motif are also processed, but not if Lys occupies P3 or Ile is in P1 .

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.
Ribosome assembly factor Mrt4 (Mrt4)
Type: Family

This entry represents the ribosome assembly factor mrt4 and related proteins. Mrt4 is a ribosomal stalk protein uL10 (also known as P0 or Rpp0) paralogue involved in ribosome biogenesis and mRNA turnover . uL10 (P0) is cytoplasmic and is present in cytoplasmic pre-60S particles and mature 60S subunits. Mrt4, however, is nuclear and has been identified in pre-60S ribosome complexes but not in mature 60S subunits, suggesting that it binds ribosomes at an early stage of assembly in the nucleolus and during assembly it is exchanged for uL10 (P0). The dual-specificity phosphatase Yvh1 is required for Mrt4 displacement from the pre-60S subunit . P0 is required for the release of Mrt4 and exchanges with this factor at the cytoplasm .
Xylanase inhibitor I-like (Xylanase_inhibitor_I-like)
Type: Domain

Xylanase inhibitor-I (TAXI-I) is a member of potent TAXI-type inhibitors of fungal and bacterial GH11 xylanases . Plants developed a diverse battery of defense mechanisms in response to continual challenges by a broad spectrum of pathogenic microorganisms. Their defense arsenal includes inhibitors of cell wall-degrading enzymes, which hinder a possible invasion and colonization by antagonists. Xylanases of fungal and bacterial pathogens are the key enzymes in the degradation of xylan in the cell wall. Plants secrete proteins that inhibit these degradation glycosidases, including xylanase.

Surprisingly, TAXI-I displays structural homology with the pepsin-like family of aspartic proteases but is proteolytically nonfunctional, because one or more residues of the essential catalytic triad are absent. It is considered a non-peptidase homologue in peptidase family A1 (MEROPS identifer A01.974). The structure of TAXI-I in complex with Aspergillus niger xylanase, illustrates the ability of tight binding and inhibition with subnanomolar affinity and indicates the importance of the C-terminal end for the differences in xylanase specificity among different TAXI-type inhibitors .

This domain is also found in basic 7S globulin (Bg7S) from soybean, which is structurally similar to xylanase inhibitor protein TAXI-I from wheat, but it lacks inhibitory activity against not only GH11 but also GH12 enzymes .
Phytepsin (Phytepsin)
Type: Domain

This entry represents a domain found in phytepsin, along with some other aspartic proteases.

Phytepsin (MEROPS identifier A01.020), is a plant homologue of mammalian lysosomal pepsins, which resides in grains, roots, stems, leaves and flowers. Phytepsin may participate in metabolic turnover and in protein processing events. In addition, it is highly expressed in several plant tissues undergoing apoptosis. Phytepsin contains an internal region consisting of about 100 residues not present in animal or microbial pepsins. This region is thus called a plant-specific insert. The insert is highly similar to saponins, which are lysosomal sphingolipid-activating proteins in mammalian cells. The saponin-like domain may have a role in the vacuolar targeting of phytepsin. Phytepsin, like its animal counterparts, possesses a topology typical of all aspartic proteases .

In Arabidopsis, there are two phytepsin genes, At1g11910 and At4g04460, but the proteins encoded by them have not been characterised.
FatB domain (FatB)
Type: Domain

Proteins with this domain are periplasmic binding proteins involved in siderophore-mediated iron uptake in some eubacterial species, such as FatB in Vibrio anguillarum and CeuE in Campylobacter coli . FatB is encoded in Vibrio anguillarum plasmid pJM1, which harbours the genes for the biosynthesis of the siderophore anguibactin and the ferric anguibactin transport proteins FatD, C, B and A . FatB is a periplasmic lipoprotein and may not be essential for ferric anguibactin transport as Vibrio anguillarum plasmid pJM1 seems to carry two ABC transporter systems participating in siderophore transport .
Sm-like protein LSm5 (LSm5)
Type: Domain

The eukaryotic like-Sm (LSm) proteins assemble into a hetero-heptameric rings (LSm2-8 or LSm1-7) around a wide spectrum of RNAs. The LSm2-8 ring functions during general RNA maturation in the nucleus, while the LSm1-7 ring functions during mRNA degradation in the cytoplasm . LSm2-8 form the core of the U6 snRNP particle that, in turn, assembles with other components to form the spliceosome which is responsible for the excision of introns and the ligation of exons . The LSm1-7 ring is involved in recognition of the 3' uridylation tag and recruitment of the decapping machinery .

Members of the LSm family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet .

This entry represents LSm5.
Non-specific lipid-transfer protein type 2 (nsLTP2)
Type: Domain

Plant nsLTPs are small, soluble proteins that facilitate the transfer of fatty acids, phospholipids, glycolipids, and steroids between membranes . In addition to lipid transport and assembly, nsLTPs also play a key role in the defense of plants against pathogens . There are two closely-related types of nsLTPs, types 1 and 2, which differ in protein sequence, molecular weight, and biological properties. nsLTPs contain an internal hydrophobic cavity, which serves as the binding site for lipids. Structure studies of rice nsLTPs show that the plasticity of the hydrophobic cavity is an important factor in ligand binding . nsLTP2s possess a more flexible central hydrophobic cavity, resulting in increased lipid transfer activity . The flexibility of the sLTP2 cavity allows its binding to rigid sterol molecules, whereas nsLTP1 cannot bind sterols despite its larger cavity size. The resulting nsLTP2/sterol complexes may bind to receptors that trigger defense responses . The nsLTP2 of Brassica rapa has been identified as a potent allergen .

This entry represents the non-specific lipid-transfer protein type 2 (nsLTP2) family.
CND41-like (CND41-like)
Type: Domain

This entry represents the aspartic peptidase domain found in CND41-like proteins. Chloroplast Nucleoids DNA-binding Protease catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in senescent leaves of tobacco. Antisense tobacco with reduced amount of CND41 maintained green leaves and constant protein levels, especially Rubisco. CND41 has DNA-binding as well as aspartic protease activities. The aspartic protease domain is located at the C terminus of the protein .

There are five paralogues in Arabidopsis thaliana, the products of the genes At1g01300, At1g79720, At3g20015, At3g61820 and At5g10770. All are included in this entry.

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.
Memapsin-like (Memapsin-like)
Type: Domain

This entry includes the peptidase domain of aspartic endopeptidases known as memapsins. In humans there are two enzymes, memapsin-1 (also known as BACE2 or beta-site of APP cleaving enzyme 1; MEROPS identifier A01.041) and memapsin-2 (BACE1; MEROPS identifier A01.004).

Beta-secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. It cleaves amyloid precursor protein (APP) to reveal the N terminus of the beta-amyloid peptides. The beta-amyloid peptides are the major components of the amyloid plaques formed in the brain of patients with Alzheimer's disease (AD). Since BACE mediates one of the cleavages responsible for generation of AD, it is regarded as a potential target for pharmacological intervention in AD. Beta-secretase is a member of pepsin family of aspartic proteases (peptidase family A1) .

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.