SII-SWORD/CoKE huggingface dataset:
Serine/threonine-protein kinase Rio1 (Ser/Thr_kinase_Rio1)
Type: Family

This entry represents serine/threonine-protein kinases (

) such as Rio1. RIO kinases are atypical members of the protein kinase family that are required for ribosome biogenesis and cell cycle progression . Rio1 is present in all organisms from archaea to mammals, and was shown to be absolutely essential in Saccharomyces cerevisiae (Baker's yeast) for the processing of 18S ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance .
Arginine N-methyltransferase 2 (Arginine_N-MeTrfase_2)
Type: Family

Arginine N-methyltransferase 2 is a delta-N-monomethylarginine transferase which monomethylates 'Arg-67' of ribosomal protein L12 .

Protein arginine methyltransferases (PRMT) have been implicated in the regulation of transcription. They are recruited to promoters via their interaction with transcription factors and exert their co-activator function by methylating arginine residues in histones and other chromatin proteins .
Pyruvate Pi dikinase regulator, chloroplast (Pyrv_Pi_dikinase_reg_chlpt)
Type: Family

This entry represents pyruvate Pi dikinase (PPDK) regulatory protein found in chloroplasts, which acts as a bifunctional serine/threonine kinase (

) and a phosphorylase (

) . This enzyme is involved in the dark/light-mediated regulation of PPDK by catalysing its phosphorylation/dephosphorylation. Dark/light-induced changes in stromal concentrations of the competing ADP and Pi substrates govern the direction of the reaction. In the dark, it phosphorylates the catalytic intermediate of PPDK (PPDK-HisP), thereby inactivating it. Light exposure induces the phosphorolysis reaction that reactivates PPDK. Unlike the kinase function which can utilise either Thr or Ser as a target, the phosphorylase function has a strict substrate requirement for threonyl phosphate .
Mitochondrial outer membrane transport complex protein Metaxin 1/3 (Metaxin1/3)
Type: Family

Metaxin is a mitochondrial outer membrane protein, which is involved in transport of proteins into the mitochondrion . Metaxin extends into the cytosol while anchored into the outer mitochondrial membrane at its C terminus.
Mitochondrial outer membrane translocase complex, subunit Tom22, plant (Tom22_pln)
Type: Family

This group represents a mitochondrial import receptor, Tom22 subunit, plant type.
Transcription factor GTE1 (GTE1)
Type: Family

This entry represents the transcription factor GTE1 from plants. Arabidopsis GTE1 is a transcription activator that plays a role in the promotion of seed germination by both negatively and positively regulating the abscisic acid (ABA) and phytochrome A (phyA) transduction pathways, respectively .
LOB domain-containing protein (LOBD)
Type: Family

This entry contains a subset of the AS2/LOB (ASYMMETRIC LEAVES 2/LATERAL ORGAN BOUNDARIES) gene family that are highly homologous and plant specific.

The N terminus contains a conserved approximately 100-amino acid domain (the LOB domain) that is present in A. thaliana proteins and in proteins from a variety of other plant species. Genes encoding LOB domain (LBD) proteins are expressed in a variety of temporal- and tissue-specific patterns, suggesting that they may function in diverse processes . The LOB domain contains conserved blocks of amino acids that identify the LBD gene family. In particular, a conserved C-x(2)-C-x(6)-C-x(3)-C motif, which is defining feature of the LOB domain, is present in all LBD proteins. It is possible that this motif forms a new zinc finger .
Putative RNA polymerase II transcriptional coactivator KELP (KELP)
Type: Family

This entry includes the putative RNA polymerase II transcriptional coactivator KELP from plants . KELP has been shown to bind to movement protein (MP) of tomato mosaic virus (ToMV) and interferes with virus cell-to-cell movement .
Chaperonin Cpn20 (Cpn20)
Type: Family

Cpn20 is a functional homologue of the cpn10 (also known as GroES) co-chaperonin, but it consists of two cpn10-like units joined head-to-tail by a short chain of amino acids. This double protein is unique to plastids and was shown to exist in plants as well plastid-containing parasites . Cpn20 seems to function as a co-chaperone, along with cpn60, and in certain cases is essential for the discharge of biologically active proteins from cpn60 . It might be an iron chaperone for superoxide dismutase in activating iron superoxide dismutase (FeSOD) .
Protein phosphatase 1, regulatory subunit 16A/B (Pase-1_reg_su_16AB)
Type: Family

Protein phosphatase 1(PP-1) is a major protein serine/threonine phosphatase that regulates a vast array of cellular processes. PP-1 action is controlled through regulatory subunits that not only dictate substrate specificity and subcellular localisation, but often regulate PP-1 activity . The myosin phosphatase targeting protein (MYPT) family consists of regulatory subunits MYPT1, MYPT2, MBS85, MYPT3 and TIMAP. MYPT family members share several conserved domains, including an RVxF motif for PP1c binding, and several ankyrin repeats that mediate protein-protein interactions .

This entry consists of protein phosphatase 1 regulatory subunits 16A (MYPT3) and 16B (TIMAP). MYPT3 and TIMAP contain a C-terminal CaaX box (a prenylation motif where 'a' indicates an aliphatic amino acid: CLLM in MYPT3 and CRIS in TIMAP), similar to that identified in the Rho family of small GTPases, which targets the proteins to the cell membrane . MYPT3 binding to PP1c inhibits its catalytic activity towards LC20, contrary to other MYPT family members . TIMAP (TGF-beta-inhibited membrane-associated protein) is primarily localised to the plasma membrane of endothelial cells . TIMAP-PP1c substrates identified include the non-integrin laminin receptor 1 (LAMR1), which is involved in regulation of cell motility and angiogenesis , and ERM (ezrin-radixin-moesin) proteins, which crosslink actin filaments with plasma membranes .
Mitogen-activated protein kinase kinase kinase 12/13 (MAP3K12_MAP3K13)
Type: Family

This entry represents mitogen-activated protein kinase kinase kinase, types 12/13 (MAP3K12 and MAP3K13), which form part of the mixed lineage kinase (MLK) family.
6,7-dimethyl-8-ribityllumazine synthase, chloroplast (DMRL_synthase_chloroplast)
Type: Family

6,7-dimethyl-8-ribityllumazine synthase (riboflavin synthase) catalyses the biosynthesis of riboflavin according to the reaction:
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
.

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. The final step in the biosynthesis of the vitamin involves the dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase. The second product, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, is recycled in the biosynthetic pathway by 6,7-dimethyl-8-ribityllumazine synthase . N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid derivatives inhibit riboflavin synthase .

This group represents a 6,7-dimethyl-8-ribityllumazine synthase, chloroplast type.
WD repeat-containing protein 55 (WDR55)
Type: Family

WDR55 is a nucleolar protein that acts as a modulator of rRNA synthesis. In plants and animals, it is involved in organ development . This entry also includes WDR55 homologues from fungi. Their function is not clear.
tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRM6)
Type: Family

TRM6, also known as Gcd10 in budding yeasts, is a substrate-binding subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyses the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA .
Mitogen-activated protein (MAP) kinase kinase kinase 8 (MAPKKK8)
Type: Family

This entry represents mitogen-activated protein kinase kinase kinase 8 (MAP3K8 or COT or TPL2) (

), which plays a role in the cell cycle. MAP3K8 is required for TLR4 activation of the MEK/ERK pathway. MAP3K8 is able to activate NF-kappa-B 1 (NFKB1) by stimulating proteasome-mediated proteolysis of NF-kappa-B 1/p105 . MAP3K8 forms a ternary complex with NFKB1 and TNIP2 . MAP3K8 is recruited to the CD40 complex via a mechanism dependent on TRAF-binding sites in CD40 .
Mitogen-activated protein (MAP) kinase kinase kinase 14 (MAPKKK14)
Type: Family

This entry represents mitogen-activated protein kinase kinase kinase 14. Mammalian MAPKKK14 (also known as NIK) is a lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity .
Nuclear receptor coactivator (Nuclear_rcpt_coactivator)
Type: Family

This group represents the nuclear receptor coactivator family, also known as the SRC/p160 nuclear receptor coactivator family, which contains proteins that are ligand-dependent transcription factors . These receptors can function as molecular switches .

NCOA1 directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion . It is involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs) . It is also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors . It plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors . It can be regulated by sumoylation and ubiquitination .
Interleukin-1 receptor-associated kinase 4 (IRAK4)
Type: Family

This entry represents Interleukin-1 receptor-associated kinase 4 (IRAK4) (

). IRAK4 is required for the efficient recruitment of IRAK1 to the interleukin-1 (IL-1) receptor complex following IL-1 engagement, triggering intracellular signalling cascades leading to transcriptional up-regulation and mRNA stabilisation . IRAK4 phosphorylates IRAK1. Pellino-2 may be a substrate for both IRAK1 and IRAK4 .
Suppressor of fused, bacterial (Suppressor_of_fused_bac)
Type: Family

Sufu, encoding the human ortholog of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signalling . It is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade , and functions by binding these proteins and preventing their translocation to the nucleus. Sufu has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signalling pathway . Homologues of Sufu have been found in bacteria, though their function is not currently known.

This entry represents a set of bacterial Sufu homologues which are predicted to function as transcriptional regulators.
Interferon regulatory factor-1/2 (IRF1/IRF2)
Type: Family

This entry represents the interferon regulatory factor 1/2.

IRF1 is a transcriptional regulator involved in the regulation of several cellular responses, such as regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage .

IRF2 is a multifunctional transcription factor that plays a pivotal role in regulation of apoptosis and cell cycle control . It also plays an important role in modulating cellular responses to interferon (IFN) and viral infection . It has an antagonistic role to IRF1 in transcriptional regulation of IFN and ISG genes . While IRF1 acts as a positive regulator, IRF2 is known to repress IFN-mediated gene expression.
Distrobrevin (Distrobrevin)
Type: Family

This entry represents distrobrevin family, including dystrobrevin alpha/beta from humans and dystrobrevin-1 (dyb-1) from C. elegans. Dyb-1 plays a role in cholinergic transmission and as a functional partner of dystrophin (dys-1), necessary for muscle maintenance . Mammalian dystrobrevins may be involved in the formation and stability of synapses .
Dystrophin-related protein 2 (Dystrophin-related_2)
Type: Family

This group represents dystrophin-related protein 2 (DRP2) . Its expression is largely confined to the vertebrate central nervous system and may have a role in the organisation of central cholinergic synapses .
Protein phosphatase 1 regulatory subunit 3B/C/D, metazoa (Pase-1_reg-su_3B/C/D_met)
Type: Family

This entry represents protein phosphatase 1 regulatory subunit 3B/C/D from animals. They act as glycogen-targeting subunits for PP1 (protein phosphatase 1) and regulate its activity .
ESCRT-1 complex, Vps37, fungi (ESCRT-1_cplx_Vps37_fungi)
Type: Family

The Endosomal Sorting Complex Required for Transport (ESCRT) complexes form the machinery driving protein sorting from endosomes to lysosomes.Saccharomyces cerevisiae ESCRT-I is a heterotrimeric complex of Vps23, Vps28, Vps37 and Mvb12 .

The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. ESCRT (endosomal sorting complex required for transport)-I, -II and -III complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles . Various Ub-binding domains (UBDs), such as UIM, UEV and NZF are found in such machineries .
Cripto-related protein 3 (Cripto-rel_3)
Type: Family

This group represents cripto-related protein 3.
ATP-NAD kinase, PpnK-type, C-terminal (ATP-NAD_kinase_PpnK-typ_C)
Type: Homologous_superfamily

ATP-NAD kinases (

) catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates as well as inorganic polyphosphate as a source of phosphorus. ATP-NAD kinase contains two domains, where the N-terminal domain has an α/β topology that is related in structure to the N-terminal of phosphofructokinase, and the C-terminal domain has an atypical β-sandwich topology made of four structural repeats of beta(3) units . This entry represents the all-beta C-terminal domain.
Inorganic polyphosphate/ATP-NAD kinase, N-terminal (ATP-NAD_kinase_N)
Type: Homologous_superfamily

ATP-NAD kinases (

) catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates as well as inorganic polyphosphate as a source of phosphorus. ATP-NAD kinase contains two domains, where the N-terminal domain has an α/β topology that is related in structure to the N-terminal of phosphofructokinase, and the C-terminal domain has an atypical β-sandwich topology made of four structural repeats of beta(3) units . This entry represents the α/β N-terminal domain.
Amidohydrolase (Amidohydrolase)
Type: Family

This entry represents a clade of the amidohydrolases. They classified as metallopeptidases belonging to MEROPS peptidase family M20 (clan MH), subfamily M20D. Included within this group are hydrolases of hippurate (N-benzylglycine), indoleacetic acid (IAA) N-conjugates of amino acids, N-acetyl-L-amino acids and aminobenzoylglutamate. These hydrolases are of the carboxypeptidase-type, most likely utilizing a zinc ion in the active site.

In higher plants, the growth hormone indole-3-acetic acid (IAA or auxin) is stored conjugated to sugar moieties via an ester linkage or to amino acids or peptides via an amide. More than 95% of the hormone in a plant can be found in the conjugated form, leaving only a small amount of free hormone available to stimulate and control cellular growth. The overall levels of active IAA in a plant can be controlled not only by the amount of IAA synthesized, but also by the quantity of IAA that is released from the conjugated state into the free state. Amidohydrolases cleave the amide bond between the auxin and the conjugated amino acid. Several IAA amidohydrolases have been isolated from Arabidopsis thaliana (Mouse-ear cress), each of these enzymes has different substrate specificities. The A. thaliana IAA amidohydrolase, IAR3, is able to cleave IAA-Alanine, while products of the other amidohydrolase genes, known as the ILR1-like family of hydrolases (ILR1, ILL1, ILL2, ILL3, and ILL5), cleave primarily IAA-Phenylalanine and IAA-Leucine .
ATP-citrate lyase/succinyl-CoA ligase, active site (Cit_synth/succinyl-CoA_lig_AS)
Type: Active_site

There are four different enzymes that share a similar catalytic mechanism which involves the phosphorylation by ATP (or GTP) of a specific histidine residue in the active site. These enzymes are: ATP citrate-lyase (

) , the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of identical subunits; Succinyl-CoA ligase (GDP-forming) (

) is a mitochondrial enzyme that catalyzes the substrate level phosphorylation step of the tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a dimer composed of an alpha and a beta subunits; Succinyl-CoA ligase (ADP-forming) (

) is a bacterial enzyme that during aerobic metabolism functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also function in the other direction for anabolic purposes. This enzyme is a tetramer composed of two alpha and two beta subunits; and Malate-CoA ligase (

) (malyl-CoA synthetase) , is a bacterial enzyme that forms malyl-CoA from malate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of two different subunits.

This pattern, which is located some 50 residues to the C-terminal of

, includes the active site phosphorylated histidine residue.
Protein kinase, ATP binding site (Protein_kinase_ATP_BS)
Type: Binding_site

Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases.

This entry represents a conserved site, which is located in the N-terminal extremity of the catalytic domain, where there is a glycine-rich stretch of residues in the vicinity of a lysine residue. It is this lysine residue that has been shown to be involved in ATP binding.

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 .
Ribulose bisphosphate carboxylase, large subunit, ferrodoxin-like N-terminal (RuBisCO_lsu_fd_N)
Type: Domain

Ribulose bisphosphate carboxylase (RuBisCO) catalyses the initial step in Calvin's reductive pentose phosphate cycle in plants as well as purple and green bacteria. It catalyzes the primary CO2 fixation step. Rubisco is activated by carbamylation of an active site lysine, stabilized by a divalent cation, which then catalyzes the proton abstraction from the substrate ribulose 1,5 bisphosphate (RuBP) and leads to the formation of two molecules of 3-phosphoglycerate .
Prolyl-tRNA synthetase, class II (Pro-tRNA_synth_II)
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 .

Proline tRNA ligase (also known as Prolyl tRNA synthetase) (

) exists in two forms, which are loosely related. The first form is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota. Proline-tRNA ligase belongs to class IIa.
F-box associated interaction domain (F-box-assoc_interact_dom)
Type: Domain

This domain occurs in a diverse superfamily of genes in plants. Most examples are found C-terminal to an F-box (

), a 60 amino acid motif involved in ubiquitination of target proteins to mark them for degradation. Two-hybid experiments support the idea that most members are interchangeable F-box subunits of SCF E3 complexes . Some members have two copies of this domain.