SII-SWORD/CoKE huggingface dataset:
CBM6/CBM35/CBM36-like 1 (CBM6-CBM35-CBM36-like_1)
Type: Domain

Carbohydrate binding module 6 (CBM6, family 6 CBM), also known as cellulose binding domain family VI (CBD VI), and related CBMs (CBM35 and CBM36) are non-catalytic carbohydrate binding domains found in a range of enzymes that display activities against a diverse range of carbohydrate targets, including mannan, xylan, beta-glucans, cellulose, agarose, and arabinans . These domains facilitate the strong binding of the appended catalytic modules to their dedicated, insoluble substrates. Many of these CBMs are associated with glycoside hydrolase (GH) domains. CBM6 is an unusual CBM as it represents a chimera of two distinct binding sites with different modes of binding: binding site I within the loop regions and binding site II on the concave face of the β-sandwich fold . CBM36s are calcium-dependent xylan binding domains . CBM35s display conserved specificity through extensive sequence similarity, but divergent function through their appended catalytic modules.

This domain is related to carbohydrate binding modules CBM6/CBM35/CBM36 and found in uncharacterised proteins from bacteria, especially Streptomyces species.
Carbohydrate-binding protein CttA, X module (CttA_X)
Type: Domain

This entry represents a putative carbohydrate-binding domain conserved in Ruminococcus, which sits N-terminal to a dockerin repeat; the protein may be a component of the Ruminococcus cellulosome system. This X module does not share similarities with other known X modules from cellulolytic bacteria and may have a structural role .
Golvesin/Xly, CBD-like (CBD-like_Golvesin-Xly)
Type: Domain

This entry represents the CBD-like domain at the C-terminal in Golvesin in amoebas, Xanthan lyase in bacteria and related proteins. This domain is predicted to fold into a β-sandwich with a topology similar to galactose binding domains. This domain can also be found in putative fibronectin proteins.

Xanthan lyase cleaves the linkage between the terminal mannosyl and glucuronyl residues of the side chain of xanthan to liberate pyruvate mannose . Golvesin is a membrane-bound protein from endosomes, vacuoles and Golgi found in Dictyostelium . They are part of the Carbohydrate binding module family 6 (CBM6, family 6 CBM), also known as cellulose-binding domain family VI (CBD VI), and related CBMs (CBM35 and CBM36). These are non-catalytic carbohydrate-binding domains found in a range of enzymes that display activities against a diverse range of carbohydrate targets, including mannan, xylan, beta-glucans, cellulose, agarose, and arabinans . These domains facilitate the strong binding of the appended catalytic modules to their dedicated, insoluble substrates. Many of these CBMs are associated with glycoside hydrolase (GH) domains. CBM6 is an unusual CBM as it represents a chimaera of two distinct binding sites with different modes of binding: binding site I within the loop regions and binding site II on the concave face of the β-sandwich fold . CBM36s are calcium-dependent xylan binding domains . CBM35s display conserved specificity through extensive sequence similarity but divergent function through their appended catalytic modules .
Lmo2686-like (Lmo2686-like)
Type: Domain

This domain is conserved in bacilli proteins that form an unusual hexameric arrangement via circular domain-swapping of a β-hairpin-beta unit. The Lmo2686 protein is found in Listeria monocytogenes and the structure has been solved (

).
CDI inhibitor, Bp1026b-like (CdiI_Bp1026b-like)
Type: Domain

CDI toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighbouring cells . Secretion of the CdiA effector protein is dependent on the outer membrane protein CdiB. An additional small immunity protein (CdiI) protects cells from autoinhibition. They are intracellular proteins that inactivate the toxin/effector protein.

This entry represents the inhibitor of the CdiA effector protein from Burkholderia pseudomallei 1026b (which is a tRNAse) .
CDI toxin, Bp1026b-like (CDI_toxin_Bp1026b-like)
Type: Domain

Contact-dependent growth inhibition (CDI) toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighbouring bacteria . CDI is mediated by the CdiB/CdiA two-partner secretion system. CdiA secretion is dependent on the outer membrane protein CdiB. The growth inhibitory activity resides within the C-terminal region of CdiA. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered .

This entry represents the C-terminal toxin domain of CdiA effector proteins. A wide variety of C-terminal toxin domains appear to exist; this particular example from Burkholderia pseudomallei 1026b and other bacteria appears to function as a Mg
2+
-dependent RNAse cleaving tRNA, most likely in the aminoacyl acceptor stem .
Antirepressor CarS (CarS_antirepressor)
Type: Domain

CarS, an antirepressor present in Cystobacterineae, recognizes repressors to turn on the photo-inducible promoter P(B). In the dark, access to the P(B) promoter is blocked by the repressor CarA . Blue light causes expression of CarS, leading the way to the CarA-CarS interaction which dismantles the CarA-operator complex, resulting in the derepression of the P(B) promoter . A parallel pathway for regulating P(B) involves the interaction of CarS with the repressor CarH, which shares the domain architecture of CarA. CarH and CarA contain an N-terminal, MerR-type winged-helix DNA-binding domain that recognizes CarS. CarS adopts an SH3-like fold with loop length variations and acts as an operator DNA mimic .
Burkholderia lethal factor 1 (BPSL1549)
Type: Family

BPSL1549, also suggested to be called Burkholderia lethal factor 1, is a protein of unknown function from Burkholderia pseudomallei, a causative agent of melioidosis (also called Whitmore's disease). This protein shows similarity to Escherichia coli cytotoxic necrotizing factor 1 which has been found to act as a potent cytotoxin against eukaryotic cells and is lethal when administered to mice . BPSL1549 expression levels correlate with suppression or promotion of pathogenic conditions. BPSL1549 inhibits helicase activity of translation initiation factor eIF4A. As yet, there is no vaccine and the organism is multidrug resistant .
USP39 (USP39)
Type: Family

This entry contains members of peptidase family C19 known as USP39 (MEROPS identifier C19.972; also known as U4/U6.U5 tri-snRNP-associated protein 2). The name is misleading because the active site residues are not conserved, and members of this cluster are known not to be ubiquitin hydrolases . Homologues are found in eukaryotes . It is a component of the spliceosome where it regulates Aurora B mRNA levels, thus playing a role in cytokinesis and in the spindle checkpoint .
Carboxypeptidase T (Carboxypeptidase_T)
Type: Domain

This entry includes the peptidase M14-like domain of carboxypeptidase (CP) T (CPT; MEROPS identifier M14.007). CPT belongs to the M14 family of metallocarboxypeptidases (MCPs) . The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity . CPT has moderate similarity to CPA and CPB, and exhibits dual-substrate specificity by cleaving C-terminal hydrophobic amino acid residues like CPA and C-terminal positively charged residues like CPB . The substrate specificity difference between CPT and CPA and CPB is ascribed to a few amino acid substitutions at the substrate-binding pocket while the spatial organization of the binding site remains the same as in all Zn-CPs . CPT has increased thermal stability in presence of Ca
2+
ions, and two disulfide bridges which give an additional stabilization factor.
Proteasome beta 3 subunit (Proteasome_beta_3)
Type: Family

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Most proteasome subunits can be classified, on the basis on sequence similarities into two groups, alpha (A) and beta (B). These are arranged in four rings of seven proteins, consisting of a ring of alpha subunits, two rings of beta subunits, and a ring of alpha subunits. In eukaryotes, each alpha and each beta ring consists of different proteins. Three of the beta subunits are peptidases in subfamily T1A, and each has a distinctive specificity (trypsin-like, chymotrypsin-like and glutamyl peptidase-like). The peptidases are N-terminal nucleophile hydrolases in which the N-terminal threonine is the nucleophile in the hydrolytic reaction . In the immunoproteasome, the catalytic components are replaced by three specialist, catalytic beta subunits . In bacteria and archaea there is only one alpha subunit and one beta subunit, and each ring is a homoseptamer.

The entry represents the proteasome beta type-3 subunit (MEROPS identifier T01.983), which is not one of the proteolytic subunits.
Proteasome subunit alpha5 (Proteasome_alpha_type_5)
Type: Family

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.

This entry represents the proteasome alpha 5 subunit (MEROPS identifier T01.975) also known as Pup2.
Penicillin G acylase, C-terminal (PGA_C)
Type: Domain

Penicillin G acylase (PGA) is the key enzyme in the industrial production of beta-lactam antibiotics. PGA hydrolyzes the side chain of penicillin G and related beta-lactam antibiotics releasing 6-amino penicillanic acid (6-APA), a building block in the production of semisynthetic penicillins. PGA is widely distributed among microorganisms, including bacteria, yeast and filamentous fungi but its in vivo role remains unclear . It is synthesized as a precursor which processes itself, comprising a signal sequence, and the A and B chains of the mature enzyme (209 and 557 residues respectively) joined by a spacer peptide of 54 amino acid residues. The AB heterodimer is produced by proteolytic removal of this spacer in the periplasm . The precursor is considered a peptidase (MEROPS family S45, MEROPS identifier S45.001). The newly-exposed N-terminal serine is the catalytic nucleophile, and PGA is a member of the Ntn hydrolase superfamily .

This entry represents the C-terminal or B domain of the mature protein, following the self-processing which produces the AB heterodimer .
Carboxypeptidase N, N-terminal domain (M14_CPN)
Type: Domain

Peptidase M14 Carboxypeptidase N (CPN, also known as kininase I, creatine kinase conversion factor, plasma carboxypeptidase B, arginine carboxypeptidase, and protaminase;

, MEROPS identifier M14.004) is an extracellular glycoprotein synthesized in the liver and released into the blood, where it is present in high concentrations. CPN belongs to the N/E subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding carboxypeptidases (CPs) which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity . CPN plays an important role in protecting the body from excessive buildup of potentially deleterious peptides that normally act as local autocrine or paracrine hormones. It specifically removes C-terminal basic residues. As CPN can cleave lysine more avidly than arginine residues it is also called lysine carboxypeptidase. CPN substrates include peptides found in the bloodstream, such as kinins (e.g. bradykinin, kalinin, Met-Lys-bradykinin), complement anaphylatoxins and creatine kinase MM (CK-MM). By removing just one amino acid, CPN can alter peptide activity and receptor binding. For example: bradykinin, a nine-residue peptide released from kiningen in response to tissue injury which is inactivated by CPN, anaphylatoxins which are regulated by CPN by the cleaving and removal of their C-terminal arginines resulting in a reduction in their biological activities of 10-100-fold, and creatine kinase MM, a cytosolic enzyme that catalyzes the reversible transfer of a phosphate group from ATP to creatine, and is regulated by CPN by the cleavage of C-terminal lysines. Like the other N/E subfamily members, two surface loops surrounding the active-site groove restrict access to the catalytic centre, thus restricting larger protein carboxypeptidase inhibitors from inhibiting CPN .

This entry represents the N-terminal catalytic domain .
Ubiquitin specific peptidase 1 (USP1)
Type: Domain

Peptidase C19 contains ubiquitin hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquitinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl group of the C-terminal Gly residue of ubiquitin. The purpose of the de-ubiquitination is thought to be editing of the ubiquitin conjugates, which could rescue them from degradation, as well as recycling of the ubiquitin. The ubiquitin/proteasome system is responsible for most protein turnover in the mammalian cell, and with over 50 members, family C19 is one of the largest families of peptidases in the human genome .

This entry encompasses ubiquitin-specific hydrolase 1 (MEROPS identifier C19.019). It is required for deubiquitination of monoubiquitinated proteins involved in various DNA repair pathways and is a key regulator of DNA repair mechanisms . Substrates include monoubiquitinated PCNA , and components FANCD2 and FANCI of the Fanconi anemia pathway, a genetic disorder that results in the inability to monoubiquitinate these components .
Eosinophil major basic protein, C-type lectin-like domain (EMBP_CTLD)
Type: Domain

This is a C-type lectin-like domain (CTLD) of the type found in the human proteins eosinophil major basic protein (EMBP) and prepro major basic protein homologue (MBPH) . CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins .

Eosinophils and basophils carry out various functions in allergic, parasitic, and inflammatory diseases. EMBP is stored in eosinophil crystalloid granules and is released upon degranulation. EMBP is also expressed in basophils. The proform of EMBP is expressed in placental X cells and breast tissue and increases significantly during human pregnancy. The proform inhibits the metallopeptidase pregnancy-associated plasma protein A and is considered to be a peptidase inhibitor (MEROPS identifier I63.001). EMBP has cytotoxic properties and damages bacteria and mammalian cells, in vitro, as well as, helminth parasites . EMBP deposition has been observed in the inflamed tissue of allergy patients in a variety of diseases including asthma, atopic dermatitis, and rhinitis. In addition to its cytotoxic functions, EMBP activates cells and stimulates cytokine production . EMBP has been shown to bind the proteoglycan heparin. The binding site is similar to the carbohydrate binding site of other classical CTLD, such as mannose-binding protein (MBP1), however, heparin binding to EMBP is calcium ion independent . MBPH has reduced potency in cytotoxic and cytostimulatory assays compared with EMBP .
MIG-17 peptidase (MIG-17)
Type: Domain

The adamalysin-like or ADAM family of metalloproteases (peptidase subfamily M12B) contains proteolytic domains from snake venoms, proteases from the mammalian reproductive tract, and the tumor necrosis factor alpha convertase, TACE. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. Some ADAM proteins contain thrombospondin repeats and are known as ADAMTS proteins .

This entry contains the MIG-17 peptidase (MEROPS identifier M12.019) found in nematodes. MIG-17 is an ADAMTS and is important for the directed migration of gonadal dorsal tip cells. It is secreted from the body wall muscle cells and localizes to the gonadal basement membrane via its prodomain , where it autoactivates .
Saccharopepsin (Saccharopepsin)
Type: Domain

Saccharopepsin (or fungal proteinase A, MEROPS identifier A01.018) is a member of the aspartic proteinase superfamily. In Saccharomyces cerevisiae, targeted to the vacuole as a zymogen, activation of saccharopepsin at acidic pH can occur by two different pathways: a one-step process to release mature saccharopepsin, involving the intervention of proteinase B, or a step-wise pathway via the auto-activation product known as pseudo-saccharopepsin. Once active, saccharopepsin is essential to the activities of other yeast vacuolar hydrolases, including proteinase B and carboxypeptidase Y. The mature enzyme is bilobal, with each lobe providing one of the two catalytically essential aspartic acid residues in the active site. The crystal structure of free saccharopepsin shows that the flap loop is atypically pointing directly into the S(1) pocket of the enzyme. Saccharopepsin preferentially hydrolyzes hydrophobic residues such as Phe, Leu or Glu at the P1 position and Phe, Ile, Leu or Ala at P1'. Moreover, the enzyme is inhibited by IA3, a natural and highly specific inhibitor produced by S. cerevisiae .
Nuclear receptor-interacting protein, peptidase domain (NRIP_C)
Type: Domain

Proteins with this domain have been described as probable nuclear receptor interacting proteins. This C-terminal domain is homologous to the retroviral aspartyl protease domain. The domain is structurally related to one lobe of the pepsin molecule. The conserved active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. This group of aspartate peptidases is classified by MEROPS as the peptidase family A28, with the identifier A28.002 .
Nucellin (Nucellin)
Type: Domain

Nucellin (MEROPS identifier A01.073) is an important regulator of a nucellar cell's progressive degradation after ovule fertilisation. This degradation is a characteristic of programmed cell death. Nucellin is a plant aspartic endopeptidase specifically expressed in nucellar cells during degradation . The enzyme is characterised by having two aspartic endopeptidase catalytic site motifs, Asp-Thr-Gly-Ser in the N-terminal and Asp-Ser-Gly-Ser in the C-terminal region, and two other regions nearly identical to two regions of plant aspartic proteases. An aspartic endopeptidase is a bilobal enzyme, with each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe may be evolved from the other through an ancient gene-duplication event. Although the three-dimensional structures of the two lobes are very similar, the amino acid sequences are more divergent, except for the conserved catalytic site motif .

This entry represents the peptidase domain of nucellin.
D-aminopeptidase DppA (DppA)
Type: Family

This entry contains the D-aminopeptidase dipeptide-binding protein (dppA; DAP dppA; MEROPS identifier M55.001). Peptide transport systems are found in many bacterial species and generally function to accumulate intact peptides in the cell, where they are hydrolysed . The dipeptide-binding protein (dppA) of Bacillus subtilis belongs to the dipeptide ABC transport (dpp) operon expressed early during sporulation. It is a binuclear zinc-dependent, D-specific aminopeptidase. The biologically active enzyme is a homodecamer with active sites buried in its channel. These self-compartmentalising proteases are characterised by an SXDXEG motif . D-Ala-D-Ala and D-Ala-Gly-Gly are the preferred substrates . Bacillus subtilis dppA is thought to function as an adaptation to nutrient deficiency; hydrolysis of its substrate releases D-Ala which can be used subsequently as metabolic fuel .
FACT complex subunit Spt16, peptidase M24-like domain (Spt16_M24)
Type: Domain

Spt6 (also known as cdc68) is a component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes . Spt16 is a non-peptidase homologue in peptidase family M24 .
Isoaspartyl-dipeptidase (Isoaspartyl-dipeptidase)
Type: Family

Isoaspartyl dipeptidase (MEROPS identifier M38.001) hydrolyzes the β-L-isoaspartyl linkages in dipeptides, as part of the degradative pathway to eliminate proteins with β-L-isoaspartyl peptide bonds, bonds whereby the β-group of an aspartate forms the peptide link with the amino group of the following amino acid. Formation of this bond is a spontaneous nonenzymatic reaction in nature and can profoundly affect the function of the protein. Isoaspartyl dipeptidase is an octameric enzyme that contains a binuclear zinc centre in the active site of each subunit and shows a strong preference of hydrolyzing Asp-Leu dipeptides .
CTP synthase GATase domain (GATase1_CTP_Synthase)
Type: Domain

This entry represents the type 1 glutamine amidotransferase (GATase1) domain found in Cytidine Triphosphate Synthetase (CTP). CTP is involved in pyrimidine ribonucleotide/ribonucleoside metabolism. CTPs produce CTP from UTP and glutamine and regulate intracellular CTP levels through interactions with four ribonucleotide triphosphates. The enzyme exists as a dimer of identical chains that aggregates as a tetramer .

CTP is derived form UTP in three separate steps involving two active sites. In one active site, the UTP O4 oxygen is activated by Mg-ATP-dependent phosphorylation, followed by displacement of the resulting 4-phosphate moiety by ammonia. At a separate site, ammonia is generated via rate limiting glutamine hydrolysis (glutaminase) activity . A gated channel that spans between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion. CTPs belong to the triad family of amidotransferases having a conserved Cys-His-Glu catalytic triad in the glutaminase active site .
Antithrombin-III, serpin domain (Antithrombin_3_serpin_domain)
Type: Domain

Antithrombin-III (AT-III), also known as serpin C1, is the most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits serine proteases of the intrinsic coagulation pathway such as thrombin and factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin . It also inhibits matriptase-3/TMPRSS7; this inhibition seems to be lost in the majority of carcinoma cells .

This entry corresponds to the antithrombin serpin domain .
Serpin H1, serpin domain (Serpin_H1_serpin_dom)
Type: Domain

Colligin 1 (also known as SERPINH1; MEROPS identifier I04.035) is a chaperone exclusive for collagen folding in the ER. Mutations in the gene cause a severe form of osteogenesis imperfecta, a connective tissue disease characterised by bone fragility and increased risk of fractures in dogs . The serpin does not inhibit serine peptidases, unlike most serpins, but has been shown to inhibit the lysosomal cysteine endopeptidase cathepsin L .

This entry represents the serpin domain of serpin H1.