SII-SWORD/CoKE huggingface dataset:
Apoptosis regulator, Bcl-2, BH2 motif, conserved site (Bcl2_BH2_motif_CS)
Type: Conserved_site

Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) . Many viruses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes preventing their target-cells from dying too soon.

All proteins belonging to the Bcl-2 family contain either a BH1, BH2, BH3, or BH4 motif. All anti-apoptotic proteins contain BH1 and BH2 motifs; some of them contain an additional N-terminal BH4 motif (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 motif (except for Bad) necessary for dimerisation with other proteins of Bcl-2 family and crucial for their killing activity; some of them also contain BH1 and BH2 motifs (Bax, Bak). The BH3 motif is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L).
Apoptosis regulator, Bcl-2, BH3 motif, conserved site (Bcl2_BH3_motif_CS)
Type: Conserved_site

Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) . Many viruses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes preventing their target-cells from dying too soon.

All proteins belonging to the Bcl-2 family contain either a BH1, BH2, BH3, or BH4 motif. All anti-apoptotic proteins contain BH1 and BH2 motifs; some of them contain an additional N-terminal BH4 motif (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 motif (except for Bad) necessary for dimerisation with other proteins of Bcl-2 family and crucial for their killing activity; some of them also contain BH1 and BH2 motifs (Bax, Bak). The BH3 motif is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L).
Apoptosis regulator, Bcl-2, BH4 motif, conserved site (Bcl2_BH4_motif_CS)
Type: Conserved_site

Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) . Many viruses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes preventing their target-cells from dying too soon.

All proteins belonging to the Bcl-2 family contain either a BH1, BH2, BH3, or BH4 motif. All anti-apoptotic proteins contain BH1 and BH2 motifs; some of them contain an additional N-terminal BH4 motif (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 motif (except for Bad) necessary for dimerisation with other proteins of Bcl-2 family and crucial for their killing activity; some of them also contain BH1 and BH2 motifs (Bax, Bak). The BH3 motif is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L).
Aminoacyl-tRNA synthetase, class I, anticodon-binding domain, subdomain 2 (aa-tRNA-synth_I_codon-bd_sub2)
Type: Homologous_superfamily

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a β-α-α-β-α topology ('SC fold') domain that contains the class I specific KMSKS motif .
Glutamate-tRNA synthetase, class I, anticodon-binding domain, subdomain 1 (Glu-tRNA-synth_I_codon-bd_sub1)
Type: Homologous_superfamily

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Structurally, an α-helix-bundle anticodon-binding domain characterises the class Ia synthetases, whereas the class Ib synthetases, GlnRS and GluRS have distinct anticodon-binding domains. The anticodon-binding domain has a multi-helical structure, consisting of two all-alpha subdomains. The Rossmann-fold, made up of alternate α-helices and β-sheets involved in ATP binding in the extended conformation, and the anticodon-binding domains are connected by a β-α-α-β-α topology ('SC fold') domain that contains the class I specific KMSKS motif .

This superfamily represents the anticodon-binding domain 1 from Glutamate-tRNA synthetase.
Uncharacterised protein family UPF0114, bacteria (UPF0114_bac)
Type: Family

This conserved hypothetical protein family with four predicted transmembrane regions is found in
Escherichia coli, Haemophilus influenzae, and Helicobacter pylori 26695, among completed genomes.

This entry represents a group of uncharacterised proteins.
Growth factor receptor NTRK (NTRK)
Type: Family

Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) .
dNTP triphosphohydrolase, type 1 (dNTPase_1)
Type: Family

This entry represents a subgroup of dNTP triphosphohydrolases mostly from gamma-proteobacteria. Proteins in this entry include dGTPase from E. coli and PA1124 (

) from Pseudomonas aeruginosa. They are triphosphohydrolases that have a preference for dGTP .
ATPase, OSCP/delta subunit, conserved site (ATPase_OSCP/d_CS)
Type: Conserved_site

ATP synthase (proton-translocating ATPase) is a component of the cytoplasmic membrane of eubacteria, the inner membrane of mitochondria, and the thylakoid membrane of chloroplasts. The ATPase complex is composed of an oligomeric transmembrane sector, called CF(0), which acts as a proton channel, and a catalytic core, termed coupling factor CF(1).

One of the subunits of the ATPase complex, known as subunit delta in bacteria and chloroplasts, or the Oligomycin Sensitivity Conferral Protein (OSCP) in mitochondria, seems to be part of the stalk that links CF(0) to CF(1). It either transmits conformational changes from CF(0) into CF(1) or is involved in proton conduction .

The different delta/OSCP subunits are proteins of approximately 200 amino-acid residues - once the transit peptide has been removed in the chloroplast and mitochondrial forms - which show only moderate sequence homology.

This entry represents a conserved site in the C-terminal section of these proteins.
Ribonuclease HII, archaea (RNase_HII_arc)
Type: Family

Ribonuclease HII is an endonuclease that specifically degrades the RNA of RNA-DNA hybrids via cleavage of the 5'-phosphomonoester. This entry contains proteins restricted to the archaea.
RNA polymerases, subunit N, zinc binding site (RNA_pol_suN_Zn-BS)
Type: Binding_site

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (

) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides. Archaebacterial subunit N (gene rpoN) is a small protein of about 8kDa, it is evolutionary related to a 8.3kDa component shared by all three forms of eukaryotic RNA polymerases (gene RPB10 in yeast and POLR2J in mammals) as well as to African swine fever virus (ASFV) protein CP80R .

This signature spans the conserved region, which is located at the N-terminal extremity of these polymerase subunits; this region contains two cysteines that binds a zinc ion .
Leucine-tRNA ligase, archaeal (Leu-tRNA-lgase_arc)
Type: Family

Leucine tRNA ligase (

) is an alpha monomer that belongs to class Ia. This entry represents a group of leucine tRNA ligases found only in Archaea.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Sulphate adenylyltransferase, prokaryotic-type (SO4_adenylyltransferase_pro)
Type: Family

ATP-sulfurylase catalyses a key reaction in the global sulfur cycle by reversibly converting inorganic sulfate with ATP to adenosine 5'-phosphosulfate (APS) and pyrophosphate (PPi) . This entry consists of sulphate adenylyltransferase or ATP-sulfurylase (

), mainly from prokaryotes. It also includes ATP-sulfurylase from the enteric protozoan parasite Entamoeba, which is closest to Synechocystis and Bacillus subtilis ATP-sulfurylases . In higher eukaryotes, APS kinase is N-terminally fused to ATP-sulfurylase.
Phosphomevalonate dehydratase small subunit (PMDh_S)
Type: Family

This entry represents Phosphomevalonate dehydratase small subunit from Aeropyrum pernix (PMDh-S) and similar prokaryotic proteins. PMDh-S is a component of a hydro-lyase that catalyses the dehydration of mevalonate 5-phosphate (MVA5P) to form trans-anhydromevalonate 5-phosphate (tAHMP) . It is involved in the archaeal mevalonate (MVA) pathway, which provides fundamental precursors for isoprenoid biosynthesis, such as isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) . Members of this family were previously annotated as aconitase X subunit 2, the swiveling domain subunit .
Origin recognition complex, subunit 3 (ORC3)
Type: Family

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 .
Origin recognition complex, subunit 5 (ORC5)
Type: Family

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 .
Cytidine deaminase, bacteria (Cytidine_deaminase_bacteria)
Type: Family

This family represents the homodimeric form of cytidine deaminase, a zinc metalloprotein. Cytidine deaminase scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis. This entry contains predominantly bacterial proteins.
Large ribosomal subunit protein uL16, conserved site (Ribosomal_uL16_CS)
Type: Conserved_site

Ribosomal protein uL16 is one of the proteins from the large ribosomal subunit from bacteria and its homologues from chloroplast and mitochondria. In Escherichia coli, uL16 is known to bind directly the 23S rRNA and to be located at the A site of the peptidyltransferase centre. uL16 is a protein of 133 to 185 amino-acid residues.

This entry represents two conserved regions in the central section of these proteins.

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 .
A-kinase anchor 110kDa (AKAP_110)
Type: Family

This family consists of several mammalian protein kinase A anchoring protein 3 (PRKA3) or A-kinase anchor protein 110kDa (AKAP 110) sequences. Agents that increase intracellular cAMP are potent stimulators of sperm motility. Anchoring inhibitor peptides, designed to disrupt the interaction of the cAMP-dependent protein kinase A (PKA) with A kinase-anchoring proteins (AKAPs), are potent inhibitors of sperm motility. PKA anchoring is a key biochemical mechanism controlling motility. AKAP110 shares compartments with both RI and RII isoforms of PKA and may function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction .
Thioesterase TesA-like (TesA-like)
Type: Domain

Thioesterase domains often occur integrated in or associated with peptide synthetases which are involved in the non-ribosomal synthesis of peptide antibiotics . Thioesterases are required for the addition of the last amino acid to the peptide antibiotic, thereby forming a cyclic antibiotic. Next to the operons encoding these enzymes, in almost all cases, are genes that encode proteins that have similarity to the type II fatty acid thioesterases of vertebrates.
Polyketide synthase-like, methyltransferase domain (MeTfrase_dom)
Type: Domain

Methyl transfer from the ubiquitous donor S-adenosyl-L-methionine (SAM) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalyzed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.

This entry represents a methyltransferase domain found in polyketide synthases such as Polyketide synthase ThaQ from Burkholderia thailandensis and is found covering the whole length of the protein in some methyltransferases involved in the biosynthesis of antiobiotics and antifungal agents .
Cell division protein FtsZ, conserved site (Cell_div_FtsZ_CS)
Type: Conserved_site

In bacteria, FtsZ is an essential cell division protein involved in the initiation of this event. It assembles into a cytokinetic ring on the inner surface of the cytoplasmic membrane at the place where division will occur. The ring serves as a scaffold that is disassembled when septation is completed. FtsZ ring formation is initiated at a single site on one side of the bacterium and appears to grow bidirectionally. In Escherichia coli, MinCD

, encoded by the MinB locus, form a complex which appears to block the formation of FtsZ rings at the cell poles, at the ancient mid cell division sites, whilst MinE, encoded at the same locus, specifically prevents the action of MinCD at mid cell.

FtsZ is a GTP binding protein with a GTPase activity. It undergoes GTP-dependent polymerisation into filaments (or tubules) that seem to form a cytoskeleton involved in septum synthesis. The structure and the properties of FtsZ clearly provide it with the capacity for the cytoskeletal, perhaps motor role, necessary for "contraction" along the division plane. In addition, however, the FtsZ ring structure provides the framework for the recruitment or assembly of the ten or so membrane and cytoplasmic proteins, uniquely required for cell division in E. coli or Bacillus subtilis, some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerise into various structures, for example a single linear polymer of FtsZ monomers, called a protofilament. Protofilaments can associate laterally to form pairs (sometimes called thick filaments), bundles (ill-defined linear associations of multiple protofilaments) or thick filaments, sheets (parallel or anti-parallel two-dimensional associations of thick filaments) and tubes (anti-parallel associations of thick filaments in a circular fashion to form a tubular structure). In addition, small circles of FtsZ monomers (a short protofilament bent around to join itself, apparently head to tail) have been observed and termed mini-rings.

FtsZ is a protein of about 400 residues which is well conserved across bacterial species and which is also present in the chloroplast of plants as well as in archaebacteria . FtsZ is a homologue of eukaryotic tubulin with which it shows structural similarity.