SII-SWORD/CoKE huggingface dataset:
SAM-dependent methyltransferase, NodS-like (SAM-MeTfrase_NodS-like)
Type: Family

This entry consists of nodulation S (NodS) proteins. The products of the rhizobial nodulation genes are involved in the biosynthesis of lipochitin oligosaccharides (LCOs), which are host-specific signal molecules required for nodule formation. NodS is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase involved in N methylation of LCOs. NodS uses N-deacetylated chitooligosaccharides, the products of the NodBC proteins, as its methyl acceptors .
Nodulation protein Z (NodZ)
Type: Family

The nodulation genes of Rhizobia are regulated by the nodD gene product in response to host-produced flavonoids and appear to encode enzymes involved in the production of a lipo-chitose signal molecule required for infection and nodule formation. NodZ is required for the addition of a 2-O-methylfucose residue to the terminal reducing N-acetylglucosamine of the nodulation signal. This substitution is essential for the biological activity of this molecule. Mutations in nodZ result in defective nodulation. nodZ represents a unique nodulation gene that is not under the control of NodD and yet is essential for the synthesis of an active nodulation signal .
Noggin (Noggin)
Type: Family

Noggin was first discovered by its ability to induce secondary axis formation in Xenopus embryos . It is a secreted homodimeric glycoprotein that serves as a BMP (bone morphogenetic protein) antagonist . It has been found that noggin arrests the differentiation of stromal cells, preventing cellular maturation . In humans increased noggin activity results in skeletal dysplasia such as proximal symphalangism (SYM1) and multiple synostosis syndrome 1 (SYNS1) . Noggin maintains prolonged growth of human embryonic stem cells in vitro and regulates the stem cell niche during neurogenesis .

This entry also includes the Trunk protein. In Drosophila, it is a secreted growth factor critical for anterior-posterior embryonic patterning. It activates the Torso (Tor) receptor tyrosine kinase pathway, which determines terminal structures like the head and tail. Trunk undergoes proteolytic cleavage to release its active C-terminal fragment, enabling localised Tor signaling despite its uniform distribution in the embryo. This cleavage is essential for its function but does not depend on Torso-like (Tsl), a perforin-like protein that instead regulates Trunk secretion . Trunk is not a direct orthologue of Noggin but shares a distant evolutionary relationship within the cysteine knot protein superfamily .
NolX (NolX)
Type: Family

This family consists of Rhizobium NolX and Xanthomonas HrpF proteins. The interaction between the plant pathogen Xanthomonas campestris pv. vesicatoria (strain 85-10) and its host plants is controlled by hrp genes (hypersensitive reaction and pathogenicity), which encode a type III protein secretion system. Among type III-secreted proteins are avirulence proteins, effectors involved in the induction of plant defence reactions. HrpF is dispensable for protein secretion but required for AvrBs3 recognition in planta, is thought to function as a translocator of effector proteins into the host cell . NolX, a Glycine max (Soybean) cultivar specificity protein, is secreted by a type III secretion system (TTSS) and shows homology to HrpF. It is not known whether NolX functions at the bacterium-plant interface or acts inside the host cell. NolX is expressed in planta only during the early stages of nodule development .
Nitrous oxide reductase accessory protein NosL (N2O_reductase_NosL)
Type: Family

NosL is one of the accessory proteins of the nos (nitrous oxide reductase) gene cluster. NosL is a monomeric protein of 18,540 MW that specifically and stoichiometrically binds Cu(I). The copper ion in NosL is ligated by a Cys residue, and one Met and one His are thought to serve as the other ligands. It is possible that NosL is a copper chaperone involved in metallocentre assembly .

This entry also contains HTH-type transcriptional repressors, including YcnK (also known as CutR). YcnK may act as a negative transcriptional regulator of YcnJ in the presence of copper and may use copper as a corepressor. The gene, ycnK, is significantly induced under copper-limiting conditions .
Viral hemorrhagic septicemia virus non-virion (Novirhabdo_Nv)
Type: Family

This family consists of several viral hemorrhagic septicemia virus non-virion (Nv) proteins. The NV protein is a nonstructural protein absent from mature virions although it is present in infected cells. The function of this protein is unknown .
ORC6, first cyclin-like domain (ORC6_cyclin_first)
Type: Domain

This entry represents the first cyclin-like domain of ORC6, a protein that directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; interacts with Spp1 and with trimethylated histone H3; phosphorylated by Cdc28 .

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 . ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle . ORC directs DNA replication throughout the genome and is required for its initiation . ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex . Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase . Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase .

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) . ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers .
Outer membrane porin F, N-terminal (OprF_membrane_N)
Type: Domain

This entry represents the N-terminal presumed membrane spanning domain of the outer membrane porin F (OprF) . This domain is involved in channel formation and is thought to form an 8-stranded β-barrel . OprF has porin activity and can form water-filled pores of variable size . Pseudomonas aeruginosa OprF exists in two different conformations, with the majority two-domain conformation that has no porin activity and the minority one-domain conformation with high porin activity and presumably consisting of a large β barrel .
RNA-dependent RNA polymerase, orbiviral (RNA_pol_orbivir)
Type: Family

This family consists of the RNA-dependent RNA polymerase protein VP1 from the Orbivirus. VP1 may have both enzymatic and structural roles in the virus life cycle .
Orthopoxvirus, Protein C1 (Orthopox_C1)
Type: Family

This family consists of several sequences which are highly related to the C1 protein of the Vaccinia virus.
Orthopoxvirus F7 (Orthopox_F7)
Type: Family

This entry represents Protein F7L from Vaccinia virus, also known as Protein OPG051, and similar sequences mainly found in orthopoxvirus. The function of the orthopoxvirus F7L proteins are unknown.
Poxvirus F8 (Poxvirus_F8)
Type: Family

This family consists of several poxvirus F8 proteins. F8 is also known as Protein OPG052. The function of this family is unknown.
PAAR motif (PAAR_motif)
Type: Repeat

The PAAR motif is usually found in pairs in a family of bacterial membrane proteins.
Elongator complex protein 4 (Elongator_complex_protein_4)
Type: Family

Elongator is a 6 subunit protein complex highly conserved in eukaryotes. The human Elongator six-subunit complex, known as holo-Elongator, has histone acetyltransferase activity directed against histone H3 and H4 . It consists of two subcomplexes, a core subcomplex (ELP1-3), and an accessory subcomplex (ELP4-6) . The elongator complex has been associated with many cellular activities, including transcriptional elongation , but its main function is tRNA modification . It is required for the formation of 5-methoxy-carbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups on uridine nucleosides present at the wobble position of many tRNAs .

This entry represents the ELP4 subunit. Mammalian ELP4 gene is implicated in rolandic epilepsy .
Phenolic acid decarboxylase (PA_de_COase)
Type: Family

This family includes several bacterial phenolic acid decarboxylase proteins. Phenolic acids, also called substituted cinnamic acids, are important lignin-related aromatic acids and natural constituents of plant cell walls. These acids (particularly ferulic, p-coumaric, and caffeic acids) bind the complex lignin polymer to the hemicellulose and cellulose in plants. The phenolic acid decarboxylase (PAD) gene (pad) is transcriptionally regulated by p-coumaric, ferulic, or caffeic acid; these three acids are the three substrates of PAD .
Pheromone biosynthesis activating neuropeptide (PBAN)
Type: Family

This family consists of several moth pheromone biosynthesis activating neuropeptide (PBAN) sequences. Female moths produce and release species specific sex pheromones to attract males for mating. Pheromone biosynthesis is hormonally regulated by the Pheromone Biosynthesis Activating Neuropeptide (PBAN) which is biosynthesised in the subesophageal ganglion (SOG) .
Phosphotransferase system, enzyme I N-terminal (PTS_EIN)
Type: Domain

This sequence identifies proteins which are a component of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), a major carbohydrate active transport system. The PTS system is found throughout the bacterial kingdom, and is responsible for the coupled phosphorylation and translocation of numerous sugars across the cytoplasmic membrane .
This entry represents the N-terminal domain of enzyme I (EIN) which transfers the phosphoryl group from phosphoenolpyruvate (PEP) to the phosphoryl carrier protein (HPr) which in turn phosphorylates a group of membrane-associated proteins, known as enzyme II.

The N-terminal domain of EI (EIN) extends from residues 1 to 259 and can be phosphorylated in a fully reversible manner by phosphorylated HPr. EIN, however, cannot be autophosphorylated by PEP .
Protein Pet122 (Pet122)
Type: Family

Pet122 is a mitochondrial-localised protein that activates initiation of translation of the mitochondrial mRNA from the COX3 gene, which encodes subunit III of cytochrome c oxidase .
Peroxisomal biogenesis factor 11 (PEX11)
Type: Family

This family consists of several peroxisomal biogenesis factor 11 (PEX11) proteins from several eukaryotic species. The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes . PEX11 genes in rice have diversification not only in sequences but also in expression patterns under normal and various stress conditions .
Phosphorylase kinase alpha/beta subunit (PHK_A/B_su)
Type: Family

This protein family is predominantly found in animals and bacteria.

Phosphorylase kinase (PHK) is a hexadecameric enzyme complex consisting of four copies each of four different subunits: alpha, beta, delta and gamma that plays a role in glycogen metabolism. During activation of glycogenolysis, this protein complex phosphorylates and activates glycogen phosphorylase (GP). The gamma subunit is the catalytic protein kinase, while alpha, beta and delta subunits control its activity. This entry represents several phosphorylase kinase regulatory alpha and beta subunits (KPBA/B), which interact directly with GP .

Mutations in the gene encoding the alpha subunit of PHK (PHKA2) have been shown to be responsible for X-linked liver glycogenosis (XLG). XLG, a frequent type of glycogen storage disease, is characterised by hepatomegaly and growth retardation .
Beta-microseminoprotein (PSP94)
Type: Family

This family consists of the protein beta-microseminoprotein/prostate-associated microseminoprotein from humans and some small serum protein from snakes. Prostatic secretory protein of 94 amino acids (PSP94), also called beta-microseminoprotein, is a small, nonglycosylated protein, rich in cysteine residues. It was first isolated as a major protein from Homo sapiens seminal plasma . The exact function of this protein is unknown.

The small serum proteins may serve as a self-defense protein against the toxic effects of the snake venom during accidental envenomation.
Putative aspartic peptidase, DUF1758 (DUF1758)
Type: Domain

This is a domain found in a group of proteins of unknown function. Most members of this entry are found in arthropods and nematodes . It seems likely that these proteins act as aspartic peptidases.
Peptidase C30, coronavirus (Peptidase_C30_CoV)
Type: Domain

This group of cysteine peptidases correspond to MEROPS peptidase family C30 (clan PA(C)). These peptidases are related to serine endopeptidases of family S1 and are restricted to coronaviruses, where they are involved in viral polyprotein processing during replication .

This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain and it is highly conserved among coronaviruses. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III. Domains I and II consist of six-stranded antiparallel β barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain, a globular cluster of five helices, has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad. In contrast to serine proteinases and other cysteine proteinases, which have a catalytic triad, there is no third catalytic residue present . Many drugs have been developed to inhibit CoV M-pro .
RNA-directed RNA polymerase, apple chlorotic leaf spot virus (RNA-dir_pol_ACLSV)
Type: Domain

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This signature is found in the RNA-direct RNA polymerase of apple chlorotic leaf spot virus and cherry mottle virus.
Domain of unknown function DUF1717 (DUF1717)
Type: Domain

The domain is found towards the N terminus of the polyprotein of Apple stem grooving virus (strain P-209) (ASGV), Citrus tatter leaf virus and from Apple stem grooving virus (strain Korea) (ASGV) (Pear black necrotic leaf spot virus) . It is a putative RNA-directed RNA polymerase/helicase: replicates genomic RNA, and might as well transcribe a subgenomic RNA coding for coat protein .
Staphopain peptidase C47 (Peptidase_C47)
Type: Family

Staphopains are one of four major families of proteinases secreted by the Gram-positive Staphylococcus aureus. These staphylococcal cysteine proteases are secreted as preproenzymes that are proteolytically cleaved to generate the mature enzyme .
Peptidase M11, gametolysin (Peptidase_M11)
Type: Domain

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 M11 (gametolysin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH .

The type example is gametolysin from the unicellular biflagellated alga, Chlamydomonas reinhardtii Gametolysin is a zinc-containing metallo-protease, which is responsible for the degradation of the cell wall. Homologues of gametolysin have also been reported in the simple multicellular organism, Volvox .
Peptidase M13, N-terminal domain (Peptidase_M13_N)
Type: Domain

This entry represents the N-terminal domain of M13 peptidases.

This group of metallopeptidases belong to the MEROPS peptidase family M13 (neprilysin family, clan MA(E)). The M13 family includes neprilysin (neutral endopeptidase, NEP, enkephalinase, CD10, CALLA,

), endothelin-converting enzyme I (ECE-1,

), erythrocyte surface antigen KELL (ECE-3), phosphate-regulating gene on the X chromosome (PHEX), soluble secreted endopeptidase (SEP), and damage-induced neuronal endopeptidase (DINE)/X-converting enzyme (XCE). These proteins consist of a short N-terminal cytoplasmic domain, a single transmembrane helix, and a larger C-terminal extracellular domain containing the active site. The cytoplasmic domain contains a conformationally-restrained octapeptide, which is thought to act as a stop transfer sequence that prevents proteolysis and secretion . Proteins in this family fulfill a broad range of physiological roles due to the greater variation in the S2' subsite allowing substrate specificity . The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH .

M13 peptidases are well-studied proteases found in a wide range of organisms including mammals and bacteria. In mammals they participate in processes such as cardiovascular development, blood-pressure regulation, nervous control of respiration, and regulation of the function of neuropeptides in the central nervous system. In bacteria they may be used for digestion of milk . The family includes eukaryotic and prokaryotic oligopeptidases, as well as some of the proteins responsible for the molecular basis of the blood group antigens e.g. Kell .
Peptidase M43, pregnancy-associated plasma-A (Peptidase_M43)
Type: Domain

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 M43 (cytophagalysin family, clan MA(M)), subfamily M43. The zinc ligands and active site residue for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH. This model includes pappalysins and related metalloprotease domains from all three kingdoms of life. The three-dimensional structure of an archaeal representative, ulilysin (MEROPS identifier M43.007), has been solved .

The type example of this family is the pregnancy-associated plasma protein A (PAPP-A; MEROPS identifier M43.004), which cleaves insulin-like growth factor (IGF) binding protein-4 (IGFBP-4), causing a dramatic reduction in its affinity for IGF-I and -II. Through this mechanism, PAPP-A is a regulator of IGF bioactivity in several systems, including the Homo sapiens ovary and the cardiovascular system .
Peptidase M56 (Peptidase_M56)
Type: Domain

This domain is found in a group of metallopeptidases belonging to MEROPS peptidase family M56 (clan M-). The predicted active site residues for members of this family occur in the motif HEXXH. The type example is BlaR1 peptidase from Bacillus licheniformis.

BlaR1 is a potential penicillin-binding protein required for induction of beta-lactamase in Bacillus licheniformis .
Peptidase S28 (Peptidase_S28)
Type: Family

This group of serine peptidases belong to MEROPS peptidase family S28 (clan SC). The predicted active site residues for members of this family and family S10 occur in the same order in the sequence: S, D, H.

These serine proteases include several eukaryotic enzymes such as lysosomal Pro-X carboxypeptidase, dipeptidyl-peptidase II, and thymus-specific serine peptidase .

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .