SII-SWORD/CoKE huggingface dataset:
DNA-directed DNA polymerase, family B, adenovirus (DNA-dir_DNA_pol_B_adenovir)
Type: Family

This entry represents a group of DNA-directed DNA polymerases from Adenovirus. They belong to the distinct subclass of the polalpha family of DNA pols that employs the precursor terminal protein (pTP) as primer .
RNA-directed RNA polymerase, phytoreovirus (RNA-dir_poll_phytoreovirus)
Type: Family

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 entry represents a RNA-directed RNA polymerase, Phytoreovirus type.
RNA-directed RNA polymerase, orthobunyavirus (RNA-dir_pol_orthobunyavirus)
Type: Family

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 entry represents a RNA-directed RNA polymerase, Orthobunyavirus type.
RNA-directed RNA polymerase, phlebovirus (RNA-dir_pol_phlebovirus)
Type: Family

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 entry represents a predicted RNA-directed RNA polymerase of Phleboviruses.
CDP-diacylglycerol-inositol 3-phosphatidyltransferase, eukaryote (CDP_diag_ino_3_P_euk)
Type: Family

This entry represents a CDP-diacylglycerol-inositol 3-phosphatidyltransferase.
3-oxoacid CoA-transferase (3-oxoacid_CoA-transferase)
Type: Family

CoA-transferases catalyse the reversible transfer of of coenzyme A from CoA-thioesters to free acids, and can be divided into three families . Family I includes transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most of the family I enzymes use acetyl-CoA or succinyl-CoA as CoA donors, and are composed of two separate polypeptides, subunits A and B, which generally aggregate as heterodimers or heterotetramers. The eukaryotic enzymes, however, are generally composed of a single two-domain polypetide representing a fusion of the A and B subunits. The transfer of CoA from one substrate to another occurs via a ping pong mechanism which involves the formation of thioester bond between CoA and a conserved glutamate residue at the active site of the enzyme .

This entry represents a family of 3-oxoacid CoA-transferases, many of which are mitochondrial.
Acid phosphatase, Aspergillus type (Acid_Pase_Asper)
Type: Family

This entry represents an acid phosphatase, Aspergillus type. Acid phosphatase is an enzyme with wide specificity that catalyses the reaction:
A phosphate monoester + H(2)O = an alcohol + phosphate

It also catalyses transphosphorylations and is competitively inhibited by phosphomycin and inorganic orthophosphate. The Emericella nidulans (Aspergillus nidulans) palC4 mutant has substantially increased acid phosphatase activity when grown on solid minimal medium under phosphate starvation at pH 6.5. The secretion of this enzyme is not necessary to regenerate inorganic phosphate from the organic phosphate pool present in yeast extract .
Protein-tyrosine phosphatase, non-receptor type-14/21 (PTP_non-rcpt_14/21)
Type: Family

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;

) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation . The PTP superfamily can be divided into four subfamilies :

(1) pTyr-specific phosphatases

(2) dual specificity phosphatases (dTyr and dSer/dThr)

(3) Cdc25 phosphatases (dTyr and/or dThr)

(4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

Receptor-like, which are transmembrane receptors that contain PTPase domains

Non-receptor (intracellular) PTPases

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif . Functional diversity between PTPases is endowed by regulatory domains and subunits.

This entry represents a tyrosine-protein phosphatase, non-receptor types 14 and 21.
Coagulation factor XII/hepatocyte growth factor activator (Coagulation_fac_XII/HGFA)
Type: Family

This entry represents coagulation factor XII/hepatocyte growth factor activator (HGFA). Both proteins included in this entry show a homologous domain structure . The proteins contain a C-terminal serine peptidase domain that belongs to MEROPS peptidase family S1A (clan PA(S)) .
Penicillin/GL-7-ACA/AHL acylase (Pen/GL7ACA/AHL_acylase)
Type: Family

Penicillin amidase or penicillin acylase catalyses the hydrolysis of benzylpenicillin to phenylacetic acid and 6-aminopenicillanic acid (6-APA) a key intermediate in the the synthesis of penicillins .

This entry also includes glutaryl-7-aminocephalosporanic-acid (GL-7-ACA) acylase, acyl-homoserine lactone (AHL) acylase QuiP and AHL acylase PvdQ.
L-2-aminoadipate reductase (Lys2)
Type: Family

This entry represents a group of L-2-aminoadipate reductase from fungi, including Lys2 from budding yeasts. Lys2 is a alpha aminoadipate reductase that catalyses the reduction of alpha-aminoadipate to alpha-aminoadipate 6-semialdehyde, the fifth step in lysine biosynthesis .
Cyclin CLN (Cyclin_CLN)
Type: Family

This entry represents a G1-class of cyclins which has so far only been identified in fungi . These proteins are important for the control of the cell cycle at the G1/S transition and interact with the cdc2 protein kinase.

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .
Small ribosomal subunit protein eS6-like (Ribosomal_eS6-like)
Type: Family

This entry represents the small ribosomal subunit protein eS6 found in eukaryotes, which was previously known as S6 . Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes and may play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.

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 .
Transcription factor, Skn7-like (Sig_transdc_resp-reg_Skn7)
Type: Family

This entry represents transcription factor, Skn7 type, including Skn7 from budding yeast and Prr1 from fission yeast .

Transcription factor Skn7 is part of a SLN1-YPD1-SKN7 two-component regulatory system, which controls gene expression in response to changes in the osmolarity of the extracellular environment . Under low osmotic conditions, it is phosphorylated and activated by the phosphorelay intermediate protein Ypd1 . Skn7 can also cooperate with heat shock factor 1 (Hsf1) to achieve maximal induction of heat shock genes in response to oxidative stress .

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 .
Vegetative storage protein/acid phosphatase (APS1/VSP)
Type: Family

This entry includes vegetative storage protein (VSP) and acid phosphatase 1 (APS1) from plants, and some uncharacterised proteins from bacteria. .

Arabidopsis VSP, including VSP1 and VSP2, are acid phosphatases involved in plant defense and flower development. Their structures have been resolved .
A-agglutinin-binding subunit Aga2 (Aga2)
Type: Family

Aga2 is an adhesion subunit of a-agglutinin of a-cells. Saccharomyces cerevisiae a and alpha cells express the complementary cell surface glycoproteins a-agglutinin and alpha-agglutinin, respectively, which interact with one another to promote cellular aggregation during fungal mating . Aga2 contains the adhesive domain, and its C-terminal 10 amino acids (sequence GSPINTQYVF) can act as a ligand for alpha-agglutinin .
5-methylcytosine restriction system component, bacterial (McrC_bac)
Type: Family

This group represents a McrBC 5-methylcytosine restriction system component. It modifies the specificity of mcrB restriction by expanding the range of modified sequences that are restricted .
Signal transduction c-di-GMP phosphodiesterase, EAL/HD-GYP domain-containing (dGMP_Pdiesterase_EAL/HD-GYP)
Type: Family

Members of this group contain signal transduction/regulatory domains EAL and modified HD-GYP. It should be noted that YuxH (ComB) protein from Bacillus subtilis, which was originally described as a transcriptional regulator of late competence genes, was later shown not to be required for this regulation .

Proteins containing these domains are an integral part or immediately downstream of the signalling cascade of two-component systems. The involvement of EAL domain in signal transduction was originally established in a study of BvgR protein, which acts as a repressor of
vrg
genes in Bordetella pertussis and is in turn controlled by the BvgAS two-component regulatory system . EAL domain was found, in tandem with GGDEF domain, in diguanylate cyclases/phosphodiesterases involved in regulation of extracellular cellulose biosynthesis by cyclic diguanylate(c-di-GMP) , a novel global second messenger in bacteria . Since the diguanylate cyclase activity has been assigned to the GGDEF domain by domain disruption experiments, the EAL domain has been predicted to act as diguanylate phosphodiesterase, which has been confirmed experimentally with Salmonella typhimurium AdrA .

HD-GYP is a conserved domain found in response regulator modules of various signal transduction systems. The involvement of the HD-GYP domain in signal transduction was originally proposed on the basis of its association with CheY-like and other signal transduction domains and was later directly demonstrated experimentally by showing that RpfG is involved in regulation of the biosynthesis of extracellular endoglucanase and polysaccharide .

A modification of the HD-GYP domain, which is found in this group, as well as in several smaller groups, lacks the conserved distal portion of the domain and has certain substitutions in the characteristic metal-binding residues of the HD superfamily phosphohydrolases, which is likely to render it catalytically inactive. Note that HD domain

is not recognised in many members of this group because it is a divergent form.
Signal transduction histidine kinase, hybrid-type, aerobic respiration control ArcB (Sig_transdc_His_kin_hyb_ArcB)
Type: Family

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 the aerobic respiration control hybrid signal transduction histidine kinases ArcB.
Adenovirus early E1A protein (Aden_E1A)
Type: Family

This group represents adenoviral early E1A proteins. The E1A protein is responsible for the transcriptional activation of the early genes with in the viral genome at the start of the infection process as well as some cellular genes .

E1A disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle . It also induces the disassembly of the E2F1 transcription factors from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes . Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. The stimulation of the progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication.
Genome polyprotein, Flavivirus (Gen_Poly_FLV)
Type: Family

This group represents a genome polyprotein from Flavivirus. The polyprotein is cleaved by peptidases (including the NS3 protein, a serine endopeptidase ) into 14 chains, including the RNA-directed RNA polymerase NS5 or non-structural protein 5, with three activities: mRNA (guanine-N(7)-)-methyltransferase (

), mRNA (nucleoside-2'-O-)-methyltransferase (

) and RNA-directed RNA polymerase (

) .
M polyprotein precursor, Orthobunyavirus type (M_poly_OrthobunV)
Type: Family

This group represents a M polyprotein precursor, Orthobunyavirus type.
Envelope glycoprotein precursor/M polyprotein precursor, Tospovirus type (M_poly_TospoV)
Type: Family

This group represents an envelope glycoprotein precursor/M polyprotein precursor, Tospovirus type.
DNA-directed DNA polymerase, family B, phi29-like virus (DNA-dir_DNA_polB_phi29_vir)
Type: Family

This group represents a family B type DNA-directed DNA polymerase found in the phi29-like viruses. They are polymerases responsible for protein-primed viral DNA replication by strand displacement with high processivity and fidelity .
Integrase, predicted (Integrase_predicted)
Type: Family

Integrases are site-specific recombinases that catalyse a diverse array of DNA rearrangements. These proteins are putative integrases found in bacteria such as Mycobacterium tuberculosis.
Putative type 4B encapsulin shell protein (ENCP4)
Type: Family

Proteins in this entry may be the encapsulin shell protein in a type 4 A-domain encapsulin nanocompartment system. Its cargo may be upstream glyceraldehyde-3-phosphate dehydrogenase . It has been shown that bacterial/archaeal encapsulin-like systems and HK97-type viruses share a common ancestor and it is likely that encapsulins have evolved from HK97-type phages.
Heme utilization protein HutZ (HutZ)
Type: Family

Members of this family are heme utilization proteins, typically designated HutZ. They are members of the PPOX family (

) and, except for the lack of an N-terminal extension, are closely related to one form of heme oxidase . Members typically are found in a three-gene operon with radical SAM enzyme HutW and a protein of unknown function, HutX.
Cobalamin (vitamin B12) biosynthesis, bifunctional CbiH/CbiC (Cbl_synth_bifunc_CbiH/CbiC)
Type: Family

This entry represents a bifunctional enzyme of the cobalamin biosynthesis pathway. They contain both CbiH precorrin-3B C(17)-methyltransferase (

,

) and CbiC precorrin-8X methylmutase (

,

). CbiH catalyses the methylation of precorrin-3B at C-17 to produce precorrin-4. CbiC catalyses catalyses a methyl rearrangement in precorrin-8 that moves the methyl group from C-11 to C-12 to produce hydrogenobyrinic acid .

CbiH belongs to the superfamily of tetrapyrrole (corrin/porphyrin) methylases (

), which includes methylases that use S-adenosylmethionine (S-AdoMet) in the methylation of diverse substrates. A number of other methylases in the cobalamin biosynthesis pathway also belong to this domain superfamily (precorrin-3 methylase,

,

, amongst others), and a fusion of precorrin-3B C17-methyltransferases with precorrin isomerase is represented by

.

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .