SII-SWORD/CoKE huggingface dataset:
Deoxyuridine triphosphate nucleotidohydrolase (dUTPase)
Type: Family

The essential enzyme dUTP pyrophosphatase (

, dUTPase) is specific for dUTP and is critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. dUTPase decreases the intracellular concentration of dUPT so that uracil cannot be incorporated into DNA .

The crystal structure of human dUTPase reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll β-barrel, with the C-terminal β-strands interchanged among the subunits. The structure is similar to that of the Escherichia coli enzyme, despite low sequence homology between the two enzymes .
Aldose 1-/Glucose-6-phosphate 1-epimerase (Aldose_1/G6P_1-epimerase)
Type: Family

Aldose 1-epimerase (

) (mutarotase) is the enzyme responsible for the anomeric interconversion of D-glucose and other aldoses between their alpha- and beta-forms. Glucose-6-phosphate 1-epimerase (

) has been shown to catalyse the interconversion between the alpha and beta anomers from at least three hexose 6-phosphate sugars (Glc6P, Gal6P, and Man6P) .
Vpu protein (Vpu)
Type: Family

The human immunodeficiency virus type 1 Vpu transmembrane protein is required for the induction of degradation human CD4 receptor degradation in the endoplasmic reticulum, and for the enhancement of virus particle release from the plasma membrane of infected cells. The cytoplasmic domain of Vpu directly interacts with the CD4 receptor, targeting it for proteasome degradation . The cytoplasmic domain encompasses the C-terminal half of the 81-residue protein, and is comprised of a few helical turns without an apparent hydrophobic core . The transmembrane domain of Vpu, found towards the N terminus, forms a cation-selective ion channel and is responsible for the enhancement of virus particle release .
rRNA small subunit methyltransferase I (rRNA_ssu_MeTfrase_I)
Type: Family

Ribosomal RNA small subunit methyltransferase I (RsmI) is an S-adenosyl-L-methionine-dependent methyltransferase that catalyses the 2-O-methylation of the ribose of cytidine 1402 (C1402) in 16S rRNA . It may play a role in fine-tuning the shape and functions of the P-site to increase the translation fidelity . In vitro, active on the assembled 30S subunit, but not naked 16S rRNA or 70S ribosomes .
DNA-directed RNA polymerase Rpb11, 13-16kDa subunit, conserved site (RNA_pol_Rpb11_13-16kDa_CS)
Type: Conserved_site

In archaea, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 12 polypeptides. Small subunits of about 13 to 16 kDa are found in all three types of eukaryotic polymerases and in archaeal polymerase, which are highly conserved. Subunits included in this entry are: Rpb11 subunit from RNA polymerase II in eukaryotes , subunit L from archaeal RNA polymerase (also known as Rpo11) and subunit Rpc19 from RNA polymerases I and II in Saccharomyces cerevisiae (Baker's yeast) .

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.
Large ribosomal subunit protein eL34 (Ribosomal_eL34)
Type: Family

This entry represents a number of eukaryotic and archaebacterial ribosomal proteins that belong to the eL34 family. These were previously known as vertebrate L34, mosquito L31 , plant L34 , yeast putative ribosomal protein YIL052c and archaebacterial L34e.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
WAP-type 'four-disulfide core' domain (WAP_dom)
Type: Domain

The four-disulfide core (4-DSC) or WAP domain comprises eight cysteine residues involved in disulfide bonds in a conserved arrangement . The four disulphide core containing Whey Acidic Proteins (WAP) are the major whey proteins in the milk of many mammals and are considered to be the prototypic members of the family. However the WAP domain is not exclusive to WAP proteins, but it is found in many other proteins, a number of which have been shown to exhibit antiproteinase function .

One or more of the WAP domains occur in the WDNM1 protein, which is involved in the metastatic potential of adenocarcinomas in rats ; Kallmann syndrome protein ; caltrin-like protein II from guinea pig , which inhibits calcium transport into spermatozoa; elafin, a serine elastase inhibitor which belongs to MEROPS inhibitor family I17 ; and papilin, a metalloendopeptidase inhibitor which belongs to MEROPS inhibitor family I2 and is effective against procollagen N-proteinase .
Neuromedin U, C-terminal (NMU_C)
Type: Domain

Neuromedin U (NmU) is a vertebrate peptide which stimulates uterine smooth muscle contraction and causes selective vasoconstriction. Like most other active peptides, it is proteolytically processed from a larger precursor protein. The mature peptides are 8 (NmU-8) to 25 (NmU-25) residues long and C-terminally amidated.

This entry represents the sequence of the C-terminal extremity of NmU, which is extremely well conserved.
Ribonuclease HepT-like (HepT-like)
Type: Family

This family includes the toxic component HepT of a type II toxin-antitoxin (TA) system, which has RNase activity. These proteins contain a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and are neutralized through tri-AMPylation by the cognate antitoxin MntA, containing a MNT (minimal nucleotidyltransferase) domain . HepT-MnA form an heterooctamer (at a 2:6 ratio), a rare organisation for this kind of TA systems. HepT dimerises and enables the formation of a deep cleft at the HEPN-domain interface, containing the RX4-6H motif (where X is any amino acid and the residue immediately after the conserved R is typically a polar amino acid) as the active site that functions as an RNA-cleaving RNase. This type II TA system regulates cell motility and confers plasmid stability . Due to the prevalence of these HEPN/MNT modules in bacteria and archaea, it has been suggested that these TA systems may also play a role in the environmental adaptation to extreme habitats . This family also includes uncharacterised putative RNases from bacteria and archaea.
AF2212-like (AF2212-like)
Type: Family

This family includes short bacterial and archaebacterial proteins, thought to be antitoxin components of the a type II toxin-antitoxin (TA) system. This entry includes AF2212 from Archaeoglobus fulgidus, which has sequence similarity with the AbrB superfamily of DNA-binding proteins, identified as antitoxins . The secondary structure of AF2212 revealed at least three β-strands that are most conserved in other AbrB superfamily members .
Geranylgeranylglyceryl phosphate synthase/Heptaprenylglyceryl phosphate synthase (GGGP_HepGP_synthase)
Type: Family

This entry represents geranylgeranylglyceryl phosphate (GGGP) synthase and Heptaprenylglyceryl phosphate (HepGP) synthase.

GGGP synthase is a prenyltransferase that catalyses the transfer of the geranylgeranyl moiety of geranylgeranyl diphosphate (GGPP) to the C3 hydroxyl of sn-glycerol-1-phosphate (G1P). This reaction is the first ether-bond-formation step in the biosynthesis of archaeal membrane lipids. This entry also matches putative glycerol-1-phosphate prenyltransferases that may catalyse the transfer of a prenyl moiety to sn-glycerol-1-phosphate (G1P) .
Signal transduction histidine kinase, phosphotransfer (Hpt) domain (Sig_transdc_His_kin_Hpt_dom)
Type: Domain

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

This entry represents a domain present at the N terminus in proteins which undergo autophosphorylation. The group includes, the gliding motility regulatory protein from Myxococcus xanthus and a number of bacterial chemotaxis proteins.
Phosphoenolpyruvate carboxykinase, GTP-utilising (PEP_carboxykinase_GTP)
Type: Family

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (

) and GTP-utilising (

) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria . Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.

PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding . With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels .

PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an α/β topology that is partly similar to one another . Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site . PCK uses an α/β/α motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.

This entry represents GTP-utilising phosphoenolpyruvate carboxykinase enzymes.
Phosphoenolpyruvate carboxykinase, N-terminal (PEP_carboxykinase_N)
Type: Homologous_superfamily

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (

) and GTP-utilising (

) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria . Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.

PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding . With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels .

PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an α/β topology that is partly similar to one another . Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site . PCK uses an α/β/α motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.

This superfamily represents the N-terminal domain found in both GTP-utilising and ATP-utilising phosphoenolpyruvate carboxykinase enzymes.
Laminin, N-terminal (Laminin_N)
Type: Domain

Laminin is a large molecular weight glycoprotein present only in basement membranes in almost every animal tissue. It is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components . Each laminin is a heterotrimer assembled from alpha, beta and gamma chain subunits, secreted and incorporated into cell-associated extracellular matrices .
CpcD-like domain (CpcD-like_dom)
Type: Domain

Ferredoxin-NADP(+) oxydoreductase (FNR) (

) transfers electrons from ferredoxin (or flavodoxin) to NADP(+) to generate NADPH. In eucaryotes, the nuclear-encoded, chloroplast-targeted enzyme contains two domains: an FAD-binding domain (see

) and an NADP(+)-binding domain. With the exception of Gloeobacter violaceus PCC 7421, the predicted sequences of all cyanobacterial petH genes, encoding FNR, correspond to a protein containing three domains. Two domains at the C terminus correspond to the FAD- and NADP(+)-binding domains of higher plants FNR protein, which compose the catalytic domains of the enzyme. The N-terminal domain is similar to phycobilisome (PBS)-associated linker proteins from numerous cyanobacteria and is associated with:

CpcD, the phycocyanin (PC)-associated, rod-capping, linker polypeptide of PBS. The similarity spans nearly the entire sequence of this linker class.

CpcC, the PC-associated rod linker polypeptide. The similarity is confined only to the C terminus of this linker class.

ApcC, the allophycocyanin (APC)-associated, core linker polypeptide. The similarity only correspond to about half of the molecule.

The CpcD-like domain has an elongated shape and consists of a three-stranded β-sheet, two α-helices, one of which has only about one turn, and the connecting random coil segments .
Tachykinin domain (Tachykinin_dom)
Type: Domain

Tachykinins are a group of biologically active peptides which excite neurons, evoke behavioral responses, are potent vasodilatators and contract (directly or indirectly) many smooth muscles. This family includes many other peptides. Tachykinins, like most other active peptides, are synthesized as larger protein precursors, protachykinins, that are enzymatically converted to their mature forms. Tachykinins are from ten to twelve residues long.
Tachykinin family (Tachykinin_fam)
Type: Family

Tachykinins are a group of biologically active peptides which excite neurons, evoke behavioral responses, are potent vasodilatators, and contract (directly or indirectly) many smooth muscles. This family includes the precursors that are enzymatically converted to their mature forms. Tachykinins are from ten to twelve residues long.
Ccc1 family (Ccc1_fam)
Type: Family

This entry represents the Ccc1 family, which consists of a group of putative vacuolar ion transporters. Proteins in this family include yeast Ccc1, which has a role in calcium and manganese homeostasis , and Arabidopsis VIT1, which serves as a vacuolar Fe2+ uptake transporter .
ATPase, V1 complex, subunit F (ATPase_V1-cplx_f_g_su)
Type: Family

This entry represents subunit F in the V1 complex of V-ATPases and Na(+)-translocating ATPase in Enterococcus hirae. Subunit F is a 16kDa protein that is required for the assembly and activity of V-ATPase, and has a potential role in the differential targeting and regulation of the enzyme for specific organelles. This subunit is not necessary for the rotation of the ATPase V1 rotor, but it does promote catalysis . In Enterococcus hirae, Na(+)-translocating ATPase extrudes sodium ions from the cytoplasm and generates the Na+ electrochemical gradient by using the energy of ATP .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
Proline dehydrogenase, bacteria and archaea (PRODH_bac_arc)
Type: Family

This entry represents a group of proline dehydrogenases from bacteria and archaea.