SII-SWORD/CoKE huggingface dataset:
Phosphatidylinositol-4-phosphate 5-kinase, plant (PIno-4-P-5_kinase_pln)
Type: Family

This entry represents a group of plant-type phosphatidylinositol-4-phosphate 5-kinases (PIP5K;

), which play an essential role in coordinating plant growth, especially in response to environmental factors. This enzyme phosphorylates phosphatidylinositol-4-phosphate to produce phosphatidylinositol-4,5-bisphosphate as a precursor of two second messengers, inositol-1,4,5-triphosphate and diacylglycerol, and as a regulator of many cellular proteins involved in signal transduction and cytoskeletal organisation. This enzyme is involved in flowering, and may suppress floral initiation by modifying the expression of genes related to floral induction. It appears to be stress-induced .
Wee1-like protein kinase (Wee1-like_protein_kinase)
Type: Family

This group represents a Wee1-like protein kinase (

), which is a key regulator for G(2)-to-M progression. This enzyme phosphorylates Tyr15 on Cdc2 (cell division control protein 2) when Cdc2 is complexed to cyclin B1, which results in blocking the progression of cells into M phase . As such, it negatively regulates the entry of a cell into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed Cdc2 before the onset of mitosis . The activity of this enzyme increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated; it is then ubiquitinated and degraded at the onset of G2/M phase.
Uncharacterised conserved protein UCP037290 (UCP037290)
Type: Family

There is currently no experimental data for members of this group. They may be distantly related to the cell division inhibitor SulA (

).
Uncharacterised conserved protein UCP037291, glutaredoxin-related (UCP037291_glutaredoxin-rel)
Type: Family

This group represents a glutaredoxin-related protein, HI0926 type.
CRH-like (CHR-like)
Type: Family

This entry represents the glycosidases CRH1, CRH2 and their homologues.

These enzymes function as GPI-lipid anchored cell wall proteins (GPI-CWP) that are localised to sites of polarised growth, particularly chitin-rich areas . These proteins are found at the incipient bud site, as a ring at the bud neck as the bud grows, and in the septum at the time of cytokinesis. The GPI-anchor is attached to the protein in the endoplasmic reticulum and serves to target the protein to the cell surface. There, the glucosamine-inositol phospholipid moiety is cleaved off, and the GPI-modified mannoprotein is covalently attached via its lipidless GPI glycan remnant to the 1,6-beta-glucan of the outer cell wall layer.
Anaphase-promoting complex subunit 4, metazoa (APC4_metazoa)
Type: Family

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .

This entry represents the anaphase-promoting complex subunit 4 (APC4) from metazoa.
Lhr-like ATP-dependent RNA helicase (Lhr-like)
Type: Family

This entry represents a family of Lhr-like ATP-dependent RNA helicases. Members include bacterial DEAD/DEAH box helicases found associated with a bacterial ATP-dependent DNA ligase, part of a four-gene system that occurs in about 12 % of prokaryotic reference genomes.

Lhr is a DNA helicase that translocates in a 3'-to-5' direction on single-stranded DNA and is likely involved in DNA repair. It is most active on three- or four-stranded forked DNA structures, while flayed substrates and Holliday junctions are unwound with slightly less efficiency. Lhr can also unwind 3'-tailed duplexes, including RNA:DNA hybrids and double-stranded DNA with a 3'-single-stranded DNA overhang. However, it does not act on blunt-ended double-stranded DNA, and its activity on substrates with a 3'-single-stranded RNA tail, such as DNA:RNA or RNA:RNA, has not been tested. Lhr is probably involved in replication-coupled DNA repair, where it remodels forked DNA to generate single-stranded regions for ATP-dependent translocation .
Signal transduction histidine kinase, MctS (Sig_transdc_His_kinase_MctS)
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 signal transduction histidine kinases such as MctS.
Lipopolysaccharide core heptose(I) kinase RfaP (Lsacc_core_hep_kinase_RfaP)
Type: Family

This entry represents the lipopolysaccharide core heptose(I) kinase RfaP (also known as Lipopolysaccharide core heptose(I) kinase WaaP), which is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region. It has previously been shown that RfaP is necessary for resistance to hydrophobic and polycationic antimicrobials in Escherichia coli, and that it is required for virulence in invasive strains of S. enterica .

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .
Nuclear mRNA export protein Sac3 (Sac3)
Type: Family

This entry represents a mRNA export factor Sac3 from budding yeasts. Sac3 is a component of the TREX-2 complex (Sac3p-Thp1p-Sus1p-Cdc31p), which functions in transcription elongation and transcription-coupled mRNA export from the nucleus to the cytoplasm . Its N terminus associates with Thp1 and Sem1 to form an mRNA-binding module, as well as with the export receptor Mex67, its C terminus interacts with Sus1, Cdc31 and the Nup1 nucleoporin, providing anchoring to the nuclear pore complex .
Transcription factor TFIIIB component B'', fungi (Bdp1_fungi)
Type: Family

Transcription by RNA polymerase III (pol III) is a complex molecular process orchestrated by the two main transcription factors, TFIIIB and TFIIIC. The TFIIIB complex can be recruited by TFIIIC to upstream DNA and form an exceptionally kinetically stable TFIIIB-DNA complex, which then recruits the Pol III enzymatic complex and helps maintain it for multiple transcription cycles in a process called facilitated recycling . Saccharomyces cerevisiae TFIIIB is a complex of three subunits, the TATA box-binding protein TBP, the TFIIB-related factor BRF, and the beta'' protein.

This entry represents transcription factor TFIIIB component beta'' (also known as Bdp1) from fungi .
Inhibin, alpha subunit (Inhibin_asu)
Type: Family

Inhibins and activins are glycoproteins, secreted by the gonads, that belong to the transforming growth factor beta family . Inhibin inhibits secretion of follicle-stimulating hormone (FSH) by the pituitary , and regulates ovarian folliculogenesis and steroidogenesis .

Inhibin has two isoforms, A and B, with the same alpha subunit but different beta subunits. Inhibin A is a dimer of alpha and beta A subunits, inhibin B is a dimer of alpha and beta B subunits. Activin A is a dimer of beta A subunits, activin AB is a dimer of beta A and beta B chains. This family represents the alpha subunit of inhibin.
Alpha-(1, 3)-fucosyltransferase, metazoan (Alpha-1_3-FUT_met)
Type: Family

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The alpha1,3-fucosyltransferase VI (FUT VI) protein is a key enzyme for synthesis of sialyl Lewis X and Lewis X in epithelial cells . Despite striking functional similarity, there is low sequence homology between the bacterial and mammalian alpha(1,3/4)-and alpha(1,2)-fucosyltransferases. Le antigen expression and fucosylation have multiple biological effects on pathogenesis and disease outcome of H. pylori . The sialyl-Lewis X (SLe(x)) determinant is important in leukocyte extravasation, metastasis and bacterial adhesion . Changes in enzyme activity and the expression levels of alpha(1,6)fucosyltransferase [alpha(1,6)FT] occur in certain types of malignant transformations. Alpha(1,6)FT activity is higher in tumour tissue than in healthy tissue. Increased alpha(1,6)FT expression is also found in tumour tissues as compared to healthy and transitional tissues, inflammatory lesions and adenomas .

This group represents an alpha-(1,3)-fucosyltransferase, metazoan type.
Alpha-(1, 3)-fucosyltransferase/alpha-(1, 4)-fucosyltransferase, plant (Alpha-1_3/4-FUT_pln)
Type: Family

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The alpha1,3-fucosyltransferase VI (FUT VI) protein is a key enzyme for synthesis of sialyl Lewis X and Lewis X in epithelial cells . Despite striking functional similarity, there is low sequence homology between the bacterial and mammalian alpha(1,3/4)-and alpha(1,2)-fucosyltransferases. Le antigen expression and fucosylation have multiple biological effects on pathogenesis and disease outcome of H. pylori . The sialyl-Lewis X (SLe(x)) determinant is important in leukocyte extravasation, metastasis and bacterial adhesion . Changes in enzyme activity and the expression levels of alpha(1,6)fucosyltransferase [alpha(1,6)FT] occur in certain types of malignant transformations. Alpha(1,6)FT activity is higher in tumour tissue than in healthy tissue. Increased alpha(1,6)FT expression is also found in tumour tissues as compared to healthy and transitional tissues, inflammatory lesions and adenomas .

This group represents an alpha-(1,3)-fucosyltransferase/alpha-(1,4)-fucosyltransferase found in plants.
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, atypical (IspG_atypical)
Type: Family

This entry includes 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, which converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4CPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the sixth step of nonmevalonate terpenoid biosynthesis. It is essential in Escherichia coli. The enzyme is described as "atypical" because it contains a partially-duplicated domain. The family is found in bacteria, where it is widely but not universally distributed, and chloroplasts, where it is essential for chloroplast development , salicylic acid-mediated disease resistance to pathogens and requires ferrdoxin as a co-factor . No homology can be detected between this family and other proteins.
Spastin (Spastin)
Type: Family

Spastin is an ATP-dependent microtubule severing protein. Microtubule severing may promote reorganisation of cellular microtubule arrays and the release of microtubules from the microtubule organising centre following nucleation .
Phosphotransferase system component IIBC, sugar-specific, predicted (PTS_IIBC_sugar_specific)
Type: Family

This group represents a predicted phosphotransferase system component IIBC, sugar-specific.
Signal transduction histidine kinase, CHASE2 sensor domain-containing, predicted (Sig_transdc_His_kin_CHASE2)
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 proteins predicted to act as signal transduction histidine kinases, most of which contain a CHASE2 sensor domains. CHASE2 extracellular sensory domains are found in at least four classes of transmembrane receptors: histidine kinases, adenylate cyclases, predicted diguanylate cyclases, and either serine/threonine protein kinases .
Methyltransferase METTL16/PsiM (METTL16/PsiM)
Type: Family

METTL16 is an U6 snRNA methyltransferase that methylates adenosine residues of a subset of RNAs. It plays a key role in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts .

This entry also includes PsiM from Psilocybe cubensis. PsiM is part of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine-derived natural product. It serves as a methyltransferase that catalyze iterative N-methyl transfer as the terminal biosynthetic step .
Sigma54-dependent transcriptional activator, RtcR (Sigma54_dep_tscrpt_act_RtcR)
Type: Family

This entry represents sigma54-dependent transcriptional activators, such as RtcR from Escherichia coli. RtcR is a transcriptional repressor of rtcBA genes and directly interacts with sigma54 factor . Bacterial transcription relies on the binding of dissociable sigma (sigma) factors to RNA polymerase (RNAP) for promoter specificity .
Serine/threonine-protein kinase Unc-51 (Ser/Thr_kinase_Unc51)
Type: Family

This entry represents serine/threonine-protein kinases (

) such as Unc-51 from Caenorhabditis elegans. Unc-51 is important for axonal elongation and axonal guidance . It is required for either the maintenance of axons (membrane turnover) or for an unknown neuronal function. C elegans worms lacking Unc-51 exhibit various abnormalities in axonal elongation and axonal structures. Unc-51 could also help control cell size along with Bec-1, as mutations in their corresponding genes results in a reduction in small body size without affecting cell number .
Uncharacterised conserved protein UCP037373, transcriptional regulator, AF0674 (UCP037373_trxn_reg)
Type: Family

This group represents a predicted transcriptional regulator, AF0674 type.
Lipase, autotransporter EstA (Lipase_autotranspt_EstA)
Type: Family

This group represents an autotransporting lipolytic enzyme, EstA type.
Ethylene-insensitive protein 2 (EIN2)
Type: Family

This entry represents ethylene-insensitive protein 2. This protein plays a central role in signalling pathways regulated by ethylene (ET), and involved in various processes including development, plant defence, senescence, nucleotide sugar flux, and tropisms .
CTP:phosphocholine cytidylyltransferase (CTP-phospocholine_CTT)
Type: Family

This family includes CTP:phosphocholine cytidylyltransferase from	Streptococcus pneumoniae, also known as Choline-phosphate cytidylyltransferase, which is involved in the biosynthesis of the phosphocholine containing cell wall constituents, teichoic acid and lipoteichoic acid, which are essential for cell separation and pathogenesis . It catalyses the activation of phosphocholine (P-Cho) to CDP-choline (CDP-Cho) . Members of this group are predominantly found in firmicutes and some proteobacterial species.
Bifunctional CTP:phosphocholine cytidylyltransferase/choline kinase (Bifunc_CCT/choline_kinase)
Type: Family

This group represents uncharacterised proteins that may be involved in LPS biosynthesis. All proteins in this group possess a choline/ethanolamine kinase domain and many also have a MobA-like NTP transferase domain.
Junctophilin (Junctophilin)
Type: Family

This entry includes junctophilin 1-4 from animals.
Thiosulphate:quinone oxidoreductase, fused subunit DoxA/ DoxD (ThioSO4-Q_OxRdtase_DoxA/D)
Type: Family

This group represents a putative thiosulphate:quinone oxidoreductase, fused subunits DoxA and DoxD.
Transforming growth factor-beta receptor, type II (Transform_growth_fac-b_typ-2)
Type: Family

This entry represents the transforming growth factor (TGF)-beta receptor type-2, which has serine/threonion kinase activity (

) and uses magnesium or manganese as a cofactor. These proteins are the receptors for TGF-beta, a large family of growth and differentiation factors that mobilise complex signalling networks to regulate cellular differentiation, proliferation, motility, adhesion, and apoptosis . On ligand binding, the type-2 TGF-beta receptor forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type-2 receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators.
ABC-type thiamin-related transport system, permease component 1, predicted (ABC_thiamin-permease_prd)
Type: Family

This group represents a predicted ABC-type thiamin-related transport system, permease component 1. It is probably part of the ABC transporter complex ykoCDEF that could transport hydroxymethylpyrimidine (HMP) and/or thiamine. It could also transport other HMP-containing products. The complex is composed of two ATP-binding proteins (ykoD), two transmembrane proteins (ykoC and ykoE) and a solute-binding protein (ykoF) .
ECF transporter, predicted substrate-specific component UCP037395 (ECF_substrate-spec_UCP037395)
Type: Family

Energy-coupling factor (ECF) transporters consist of a substrate-specific component (known as the S component), and an energy-coupling module . The substrate-binding component is a small integral membrane protein which captures specific substrates and forms an active transporter in the presence of the energy-coupling AT module. The energy coupling module is composed of an ATPase typical of the ATP binding cassette (ABC) superfamily (A component) and a characteristic transmembrane protein (T component). Unlike the ABC transporters, an energy coupling module can be shared between multiple different substrate-binding components.

This entry represents the substrate specific component of a predicted ECF-type uncharacterised transport system.
Bone morphogenetic protein 3/3B (BMP3/BMP3B)
Type: Family

This group includes two members of the TGF-beta superfamily: bone morphogenetic protein 3 (BMP3) and bone morphogenetic protein 3B (BMP3B), also known as growth differentiation factor 10 (GDF10). Together they represent a subgroup of the BMP family. They are involved in development and organogenesis. In developing embryos, they have different dorsalising activities . BMP3 is a negative regulator of bone density . BMP3B plays an inhibitory role in the process of osteoblast differentiation .
DNA (cytosine-5)-methyltransferase 1-like (DNMT1-like)
Type: Family

This entry represents DNA (cytosine-5)-methyltransferase 1 (Dnmt1;

), which methylates CpG residues, with a preference for hemimethylated DNA. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Dnmt1 mediates transcriptional repression (silencing) by establishing a repressive transcription complex where the N terminus of Dnmt1 binds to HDAC2 (histone deacetylase-2) as well as to DMAP1 (Dnmt1-associated protein) . LSH, which is related to the SNF2 chromatin-remodelling ATPases, is also required for efficient DNA methylation .
Uncharacterised conserved protein UCP037409, membrane transporter, MTH672 (UCP037409_transporter)
Type: Family

This group represents a predicted membrane transporter, MTH672 type.