SII-SWORD/CoKE huggingface dataset:
Uncharacterised protein YodQ-like (YodQ-like)
Type: Family

Proteins in this family have been inferred by homology as being related to both ArgE (N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine deformylase) and DapE (succinyl-diaminopimelate desuccinylase). The family includes yodQ from Bacillus subtilis, which is part of a transcriptional unit (yodT-yodS-yodR-yodQ-yodP-kamA) whose expression is upregulated during sporulation, and that may be involved in the production of N-acetyl-beta-lysine .
RNA cytidine acetyltransferase NAT10 (NAT10)
Type: Family

RNA cytidine acetyltransferase NAT10 has specificity toward both 18S rRNA and tRNAs and catalyzes the formation of N(4)-acetylcytidine at two positions in 18S rRNA. NAT10 is required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis . NAT10 also catalyzes the formation of N(4)-acetylcytidine at a single position in serine and leucine tRNAs. The tRNA-binding adapter protein TAN1 is required for full tRNA acetyltransferase activity but not for 18S rRNA acetylation .

Human NAT10 is a lysine acetyltransferase that targets microtubules and histones, and plays an important role in cell division. It is highly expressed in malignant tumors .
NAD-dependent formate dehydrogenase (FDH_NAD-dep)
Type: Family

NAD-dependent formate dehydrogenase (FDH) catalyzes the NAD+-dependent oxidation of a formate anion to carbon dioxide coupled with the reduction of NAD+ to NADH. Formate/glycerate and related dehydrogenases of the D-specific 2-hydroxy acid dehydrogenase family have 2 highly similar subdomains of the α/β form, with NAD binding occurring in the cleft between subdomains. NAD contacts are primarily to the Rossmann-fold NAD-binding domain which is inserted within the linear sequence of the more diverse flavodoxin-like catalytic subdomain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. FDHs of this family contain no metal ions or prosthetic groups. Catalysis occurs though direct transfer of the hydride ion to NAD+ without the stages of acid-base catalysis typically found in related dehydrogenases. FDHs are found in all methylotrophic microorganisms in energy production from C1 compounds such as methanol, and in the stress responses of plants . NAD-dependent FDH is useful in cofactor regeneration in asymmetrical biocatalytic reduction processes, where FDH irreversibly oxidizes formate to carbon dioxide, while reducing the oxidized form of the cofactor to the reduced form.
Adenylate kinase, conserved site (Adenylat_kinase_CS)
Type: Conserved_site

Adenylate kinase (EC 2.7.4.3) (AK) is a small monomeric enzyme that catalyzes the reversible transfer of MgATP to AMP (MgATP + AMP = MgADP + ADP).

In mammals there are three different isozymes:

AK1 (or myokinase), which is cytosolic.

AK2, which is located in the outer compartment of mitochondria.

AK3 (or GTP:AMP phosphotransferase), which is located in the mitochondrial matrix and which uses MgGTP instead of MgATP.

The sequence of AK has also been obtained from different bacterial species and from plants and fungi.

Two other enzymes have been found to be evolutionary related to AK. These are:

Yeast uridylate kinase (EC 2.7.4.-) (UK) (gene URA6) which catalyzes the transfer of a phosphate group from ATP to UMP to form UDP and ADP.

Slime mold UMP-CMP kinase (EC 2.7.4.14) which catalyzes the transfer of a phosphate group from ATP to either CMP or UMP to form CDP or UDP and ADP.

Several regions of AK family enzymes are well conserved, including the ATP- binding domains. This entry represents a conserved site that includes an aspartic acid residue that is part of the catalytic cleft of the enzyme and that is involved in a salt bridge. It also includes an arginine residue whose modification leads to inactivation of the enzyme.
Pyroglutamyl peptidase I, Glu active site (PGPEP1_Glu_AS)
Type: Active_site

Pyroglutamyl peptidase I (

; MEROPS identifiers C15.001 (prokaryote) and C15.010 (chordate)) (also known as pyrrolidone-carboxylate peptidase, PYRase) is the enzyme that selectively removes pyroglutamate (pGlu) from the N terminus of proteins and peptides. PGP-I is widely found in bacteria, plants and animals .

In bacteria and archebacteria PYRase (gene pcp) is a protein of 22-24kDa. It is a cysteine protease with a Cys-His-Glu catalytic triad . This entry represents the signature around the glutamate active site residue.
Pyroglutamyl peptidase I, Cys active site (PGPEP1_Cys_AS)
Type: Active_site

Pyroglutamyl peptidase I (

) (also known as PGP-1, pyrrolidone-carboxylate peptidase, PYRase) is the enzyme that selectively removes pyroglutamate (pGlu) from the N terminus of proteins and peptides. PGP-I is widely found in bacteria, plants and animals .

In bacteria and archebacteria PYRase (gene pcp) is a protein of 22-24kDa. It is a cysteine protease with a Cys-His-Glu catalytic triad . This entry represents the cysteine active site.
Second polo-box domain (POLO_box_2)
Type: Domain

The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides .

This entry represents the second polo-box domain found in Plk1, Plk2 and Plk3.
Plk4, C-terminal polo-box domain (POLO_box_Plk4_C)
Type: Domain

The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides .

This entry represents the C-terminal (third) polo-box domain of Plk4.
Ribonuclease T2, eukaryotic (Ribonuclease_T2_eukaryotic)
Type: Family

Ribonuclease T2 (RNase T2) is a widespread family of secreted RNases found in every organism examined thus far. This family includes RNase Rh, RNase MC1, RNase LE, and self-incompatibility RNases (S-RNases) . Plant T2 RNases are expressed during leaf senescence in order to scavenge phosphate from ribonucleotides. They are also expressed in response to wounding or pathogen invasion. S-RNases are thought to prevent self-fertilization by acting as selective cytotoxins of "self" pollen. Generally, RNases have two distinct binding sites: the primary site (B1 site) and the subsite (B2 site), for nucleotides located at the 5'- and 3'- terminal ends of the sissile bond, respectively.

This entry includes the eukaryotic RNase T2 family members.
Plk4, second cryptic polo-box domain (POLO_box_Plk4_2)
Type: Domain

This entry represents the second (cryptic) polo-box domain of Plk4 and similar proteins mainly found in animals.

The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides .
Plk4, first cryptic polo-box domain (POLO_box_Plk4_1)
Type: Domain

The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides .

This entry represents the first (cryptic) polo-box domain of Plk4.
First polo-box domain (POLO_box_1)
Type: Domain

The polo-like Ser/Thr kinases (Plk1, Plk2/Snk, Plk3/Prk/Fnk, Plk4/Sak, and the inactive kinase Plk5) play various roles in cytokinesis and mitosis. At their C terminus, they contain a tandemly repeated polo-box domain (PBD) (in the case of Plk4, a tandem repeat of cryptic PBDs is found in the middle of the protein followed by a C-terminal single repeat), which appears to be involved in autoinhibition and in mediating the subcellular localization. The latter may be controlled via interactions between the polo-box domain and phospho-peptide motifs. The phosphopeptide binding site is formed at the interface between the two tandemly repeated PBDs. The PBDs of Plk4/Sak appear unique in participating in homodimer interactions, though it is not clear whether and how they interact with phosphopeptides .

This entry represents the first polo-box domain found in Plk1, Plk2, Plk3, and Plk5.
Polo-like kinase 1, catalytic domain (PLK1_cat)
Type: Domain

Serine/Threonine Kinases (STKs) catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Polo-like kinases (PLKs) are serine/threonine kinases that play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes .

PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase . It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations . PLK1 is overexpressed in many human cancers and is associated with poor prognosis .

This entry represents the N-terminal catalytic kinase domain of PLK1.
Picornavirus/Calicivirus coat protein (Rhv-like)
Type: Domain

This domain occurs in the capsid proteins of picornaviruses and caliciviruses. They are non-enveloped plus-strand ssRNA animal viruses. The Picornaviridae family includes rhinovirus (common cold), poliovirus, hepatitis A virus, foot-and-mouth disease virus and encephalomyocarditis virus. The common structure of this domain consists of an 8-stranded β sandwich .
dUTPase, trimeric (dUTPase_trimeric)
Type: Domain

Trimeric dUTP diphosphatases (dUTP nucleotidohydrolases or dUTPases), are the most common family of dUTPase, found in bacteria, eukaryotes, and archaea. They catalyze the hydrolysis of the dUTP-Mg complex (dUTP-Mg) into dUMP and pyrophosphate. This reaction is crucial for the preservation of chromosomal integrity as it removes dUTP and therefore reduces the cellular dUTP/dTTP ratio, and prevents dUTP from being incorporated into DNA. It also provides dUMP as the precursor for dTTP synthesis via the thymidylate synthase pathway. dUTPases are homotrimeric, except some monomeric viral dUTPases, which have been shown to mimic a trimer. Active sites are located at the subunit interface .

This entry represents the main structural domain, which folds into an eight-stranded jelly-roll β barrel.
Valyl tRNA synthetase, anticodon-binding domain (Anticodon_Ia_Val)
Type: Domain

This domain is found in valyl tRNA synthetases (ValRS), which belong to the class Ia aminoacyl tRNA synthetases . It lies C-terminal to the catalytic core domain, and recognizes and specifically binds to the tRNA anticodon. ValRS catalyzes the transfer of valine to the 3'-end of its tRNA.
Methionine synthase, B12-binding domain (Met_synthase_B12-bd)
Type: Domain

This domain is the B12 binding domain of methionine synthase. Methionine synthase binds methylcobalamin (B12), which it uses as an intermediate methyl carrier from methyltetrahydrofolate (CH3H4folate) to homocysteine to yield tetrahydrofolate and L-methionine .
Isoleucyl tRNA synthetase type 1, anticodon-binding domain (Anticodon_Ile_BEm)
Type: Domain

This domain is found in isoleucyl tRNA synthetases (IleRS), which belong to the class Ia aminoacyl tRNA synthetases. It lies C-terminal to the catalytic core domain, and recognizes and specifically binds to the tRNA anticodon. IleRS catalyzes the transfer of isoleucine to the 3'-end of its tRNA .
Isoleucyl tRNA synthetase type 2, anticodon-binding domain (Anticodon_Ile_ABEc)
Type: Domain

This domain is found in isoleucyl tRNA synthetases (IleRS), which belong to the class Ia aminoacyl tRNA synthetases. It lies C-terminal to the catalytic core domain, and recognizes and specifically binds to the tRNA anticodon. It is found in bacterial, archaeal, and eukaryotic IleRS proteins. IleRS catalyzes the transfer of isoleucine to the 3'-end of its tRNA .
TATA-box binding protein, eukaryotic (TBP_eukaryotic)
Type: Family

The TATA-box binding protein (TBP) is required for the initiation of transcription by RNA polymerases I, II and III, from promoters with or without a TATA box . TBP associates with a host of factors, including the general transcription factors SL1, TFIIA, -B, -D, -E, and -H, to form huge multi-subunit pre-initiation complexes on the core promoter. Through its association with different transcription factors, TBP can initiate transcription from different RNA polymerases. There are several related TBPs, including TBP-like (TBPL) proteins . TBP binds directly to the TATA box promoter element, where it nucleates polymerase assembly, thus defining the transcription start site.

The C-terminal core of TBP (~180 residues) is highly conserved and contains two 77-amino acid repeats that produce a saddle-shaped structure that straddles the DNA; this region binds to the TATA box and interacts with transcription factors and regulatory proteins . By contrast, the N-terminal region varies in both length and sequence.

This entry refers to TBPs found in eukaryotes.
TATA-box binding protein, archaea (TBP_archaea)
Type: Family

This entry refers to TBPs found in archaea.

The TATA-box binding protein (TBP) is required for the initiation of transcription by RNA polymerases I, II and III, from promoters with or without a TATA box . TBP associates with a host of factors, including the general transcription factors SL1, TFIIA, -B, -D, -E, and -H, to form huge multi-subunit pre-initiation complexes on the core promoter. Through its association with different transcription factors, TBP can initiate transcription from different RNA polymerases. There are several related TBPs, including TBP-like (TBPL) proteins . TBP binds directly to the TATA box promoter element, where it nucleates polymerase assembly, thus defining the transcription start site.

The C-terminal core of TBP (~180 residues) is highly conserved and contains two 77-amino acid repeats that produce a saddle-shaped structure that straddles the DNA; this region binds to the TATA box and interacts with transcription factors and regulatory proteins . By contrast, the N-terminal region varies in both length and sequence.
Pumilio, RNA binding domain (Pumilio_RNA-bd)
Type: Domain

Puf repeats (also labelled PUM-HD or Pumilio homology domain) mediate sequence specific RNA binding in fly Pumilio, worm FBF-1 and FBF-2, and many other proteins such as vertebrate Pumilio . These proteins function as translational repressors in early embryonic development by binding to sequences in the 3' UTR of target mRNAs , such as the nanos response element (NRE) in fly Hunchback mRNA, or the point mutation element (PME) in worm fem-3 mRNA. Other proteins that contain Puf domains are also plausible RNA binding proteins. Yeast PUF1 (JSN1), for instance, appears to contain a single RNA-recognition motif (RRM) domain. Puf repeat proteins have been observed to function asymmetrically and may be responsible for creating protein gradients involved in the specification of cell fate and differentiation. Puf domains usually occur as a tandem repeat of 8 domains. This domain encompasses all 8 tandem repeats . Some proteins may have fewer (canonical) repeats.
Phosphatase NudJ (NudJ)
Type: Family

NudJ is a member of the Nudix hydrolase superfamily. Unlike the other Nudix nucleoside triphosphatases, the product of the reaction catalyzed by NudJ is phosphate instead of pyrophosphate. NudJ hydrolyses 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate (HMP-PP) to 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate (HMP-P), and thiamine pyrophosphate (TPP) to thiamine monophosphate (TMP). Other substrates are hydrolysed, such as MeO-HMP-PP, CF(3)-HMP-PP, MeO-TPP, and nucleoside tri- and diphosphates. A magnesium ion is required as a co-factor .
Phenylalanly tRNA synthetase, tRNA-binding-domain (tRNA_bind_bactPheRS)
Type: Domain

This entry represents the tRNA-binding-domain of prokaryotic phenylalanyl tRNA synthetase (PheRS) beta chain. PheRSs belong structurally to class II aminoacyl tRNA synthetases (aaRSs), but because they aminoacylate the 2'OH of the terminal ribose of tRNA, they belong functionally to class I aaRSs. PheRS adopts the alpha2beta2 tetrameric structure in prokaryotic and eukaryotic cytoplasmic enzymes , with both subunits required for aminoacylation of the tRNA. All four subunits in the tetramer interact with each other and with both bound tRNA substrates . This domain has general tRNA binding properties and is believed to direct tRNAphe to the active site of the enzyme .
GDP-mannose mannosyl hydrolase (GDPMH)
Type: Family

GDP-mannose glycosyl hydrolase (AKA GDP-mannose mannosyl hydrolase (GDPMH)) is a member of the Nudix hydrolase superfamily. This class of enzymes is unique from other members of the superfamily in two aspects. First, it contains a modified Nudix signature sequence. The slight changes to the conserved sequence motif, GX5EX7REUXEEXGU, where U = I, L or V, are believed to contribute to the removal of all magnesium binding sites but one, retaining only the metal site that coordinates the pyrophosphate of the substrate. Secondly, it is not a pyrophosphatase that substitutes at a phosphorus; instead, it hydrolyzes nucleotide sugars such as GDP-mannose to GDP and mannose, cleaving the phosphoglycosyl bond by substituting at a carbon position . GDP-mannose provides mannosyl components for cell wall synthesis and is required for the synthesis of other glycosyl donors (such as GDP-fucose and colitose) for the cell wall. The importance of GDP-sugar hydrolase activities is thus closely related to the regulation of cell wall biosynthesis. Enzymes in this family are believed to regulate the concentration of GDP-mannose and GDP-glucose in the bacterial cell wall .
Nudix motif 17 domain (Nudt17_dom)
Type: Domain

This Nudix domain is found in nucleoside diphosphate-linked moiety X motif 17 proteins, which are uncharacterised proteins that probably hydrolyse nucleoside diphosphate derivatives.

The Nudix superfamily is widespread among eukaryotes, bacteria, archaea and viruses and consists mainly of pyrophosphohydrolases that act upon substrates of general structure NUcleoside DIphosphate linked to another moiety, X (NDP-X) to yield NMP plus P-X. Such substrates include (d)NTPs (both canonical and oxidised derivatives), nucleotide sugars and alcohols, dinucleoside polyphosphates (NpnN), dinucleotide coenzymes and capped RNAs. However, phosphohydrolase activity, including activity towards NDPs themselves, and non-nucleotide substrates such as diphosphoinositol polyphosphates (DIPs), 5-phosphoribosyl 1-pyrophosphate (PRPP), thiamine pyrophosphate (TPP) and dihydroneopterin triphosphate (DHNTP) have also been described. Some superfamily members, such as Escherichia coli MutT, have the ability to degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. In procaryotes and simple eukaryotes, the number of Nudix genes varies from 0 to over 30, reflecting the metabolic complexity and adaptability of the organism. Nudix hydrolases are typically small proteins, larger ones having additional domains with interactive or other catalytic functions .
Undecaprenol kinase (UDPK)
Type: Family

This mostly bacterial family of homo-trimeric integral membrane enzymes, the products of the dgkA gene, catalyzes the ATP-dependent phosphorylation of undecaprenol to undecaprenyl phosphate . C55-isoprenyl (undecaprenyl) pyroposphate acts as a scaffold for the assembly of peptidoglycan components; undecaprenol kinase (UDPK) is involved in recycling undecaprenyl units for re-use in the peptidoglycan biosynthesis. UDPK does not participate in the de-novo biosynthesis of undecaprenyl phosphate. Gram-positive bacteria have a large pool of free undecaprenol, in contrast to Gram-negative bacteria. UDPK may also play a role in a stress-induced pathway that affects the function of ribosomes. In Streptococcus mutans, UDPK has been shown to be required for biofilm formation, such as in the case of smooth surface dental caries . Members of the UDPK family have low activity as diacylglycerol kinases (DAGK), and many of them are annotated as DAGKs .
Diacylglycerol kinase, prokaryotic (DAGK_prok)
Type: Family

This mostly bacterial family of homo-trimeric integral membrane enzymes, the products of the dgkA gene, catalyzes the ATP-dependent phosphorylation of diacylglycerol to phosphatidic acid. Escherichia coli DAGK participates in the membrane-derived oligosaccharide cycle (MDO cycle) by recycling lipids to restore phosphatidylglycerols that were used up in the biosynthesis of MDOs. DAGK also recycles diacylglycerols that are produced during the biosynthesis of lipopolysaccharides (LPS) back to phospholipids. DAGK is not the main source of phosphatidic acid in de novo biosynthesis of glycerophospholipids. Escherichia coli DAGK has low activity as an undecaprenol kinase .