SII-SWORD/CoKE huggingface dataset:
RNA editing complex, structural subunit MP63 (RNA_edit_cplx_Nase-su_MP63)
Type: Family

This entry represents structural subunit MP63 from the RNA editing complex found in Trypanosoma and Leishmania. The editing process is performed by the editosome, a multi-protein complex that catalyses the insertion and deletion of uridylates (U) that occurs during RNA editing. Uridylate insertion/deletion editing, which appears to be unique to these organisms, processes most mitochondrial pre-mRNAs to produce mature mRNAs. Editosomes consist of several components and in Trypanosoma these include: REL1/MP52 and REL2/Mp48 RNA ligases; MP18, MP42, MP63 and MP81 that contain zinc fingers .
Uncharacterised conserved protein UCP037004 (UCP037004)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Wax synthase, Magnoliopsida (Wax_synthase_Magnoliopsida)
Type: Family

This entry represents a group of long-chain-alcohol O-fatty-acyltransferases (wax synthases) from flowering plants. The enzyme from Jojoba has been characterised and catalyses the final step in the synthesis of long-chain linear esters (waxes) . This family also includes acyl-CoA--sterol O-acyltransferase (ASAT1, AT3G51970), a membrane-bound O-acyltransferase involved in the esterification of cycloartenol .
Splicing factor 3B, subunit 5 (Splicing_factor_3B_subunit_5)
Type: Family

The splicing factor SF3b is a multiprotein complex essential for the accurate excision of introns from pre-messenger RNA. This entry represents the subunit 5 of SF3b .
Serine/threonine-protein kinase, SIK1/2 (Ser/Thr_kinase_SIK1/2)
Type: Family

This entry represents the salt-inducible protein kinases, SIK1 and SIK2, which are serine/threonine-protein kinases primarily activated by the master kinase LKB1 (STK11). SIK1 is involved in a variety of processes, such as cell cycle regulation, gluconeogenesis and lipogenesis regulation and muscle growth . SIK2 phosphorylates insulin receptor substrate-1 (IRS1) in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction, and may have a role in the development of insulin resistance in diabetes [

. SIK1/2 inhibit CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signalling .

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 .
Peptidase S54, rhomboid-like, Rom4/Rom5, apicomplexa (Pept_S54_Rhomboid-like_Rom4/5)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This entry represents Apicomplexa rhomboid-like proteins (

), Rom4/Rom5, which are members of the S54 peptidase family of proteins . These proteins are putative serine protease involved in intra-membrane proteolysis and the subsequent release of polypeptides from their membrane anchors. They cleave type-1 transmembrane domains using a catalytic triad composed of serine, histidine and asparagine contributed by different transmembrane domains.
Molecular chaperone regulator BAG-1 (BAG-1)
Type: Family

This group represents a molecular chaperone regulator BAG-1 . BAG-1 contains a BAG domain that is formed by two antiparallel helices, while the third helix is extended away and stabilized by crystal-packing interactions .

BAG-family proteins contain a single BAG domain, except for human BAG-5 which has four BAG repeats. The BAG domain is a conserved region located at the C terminus of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. BAG family proteins regulate chaperone protein activities through their interaction with Hsc70/Hsp70 .
Biliverdin reductase A (Biliverdin_Rdtase_A)
Type: Family

This entry represents biliverdin reductase A enzymes (

), reduces biliverdin (the product of haem oxygenases HO-1 and HO-2 activity) to the antioxidant bilirubin. It works by catalysing the reduction of the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor. This reaction is involved in the protohaem degradation pathway as part of porphyrin metabolism. Some enzymes are thought to use zinc as a cofactor. Human biliverdin reductase may also functions as a kinase and as a transcription factor in the MAPK (mitogen-activated protein kinase) signalling cascade .
Saimiri transformation-associated protein (StpC)
Type: Family

Herpesvirus saimiri protein StpC is an oncoprotein that cooperates with Tip to stimulate NF-kappaB activity and interleukin-2 gene expression .
BTB-kelch protein (BTB-kelch_protein)
Type: Family

Proteins in this family contain an N-terminal BTB domain and the C-terminal Kelch motifs. The BTB/POZ domain facilitates protein binding. The Kelch motif is a 50-residue motif named after the Drosophila mutant in which it was first identified . This sequence motif represents one β-sheet blade, and several of these repeats can associate to form a β-propeller. Some members in this family also contain a BACK domain, which is a conserved 130-residue region between the BTB domain and Kelch motifs. BTB-kelch protein family includes KLHL and part of the KBTBD subfamilies, which encompass structurally related molecules that differ in the types and numbers of their protein domains.

KBTBD subfamily typically possess a BTB and BACK domain and two to four Kelch motifs . It's worth noting that not all the KBTBD subfamily members are in this entry.
Bombyxin (Bombyxin)
Type: Family

Bombyxin is a brain peptide responsible for activation of prothoracic glands to produce ecdysone in insects . When cleaved, bombyxins produce both subunits of the biologically active heterodimer. Several molecular species of bombyxin have now been identified in Bombyx, Agrius and Samia moth species. Both bombyxin and insulin contain six cysteine residues with identical distributions and are predicted to have similar tertiary structures, especially in their core regions . They are not functionally equivalent. However, the similarity to insulin has prompted speculation that it may play a role in the regulation of growth, and it has been shown to act as a growth factor for wing imaginal discs and midgut stem cells in some lepidopteran species .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)
Uncharacterised conserved protein UCP037052 (UCP037052)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in archaea.
Uncharacterised conserved protein UCP037053 (UCP037053)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Insulin-like peptide 6 (Insulin-like_pep_6)
Type: Family

This group represents an insulin-like peptide 6.
P-loop ATP/GTP binding protein, All4644, predicted (P-loop_ATP/GTP-bd_All4644_prd)
Type: Family

This group represents a predicted P-loop ATP/GTP binding protein, All4644 type.
Uncharacterised conserved protein UCP037087 (UCP037087)
Type: Family

There is currently no experimental data for members of this group. They contain a cupin superfamily domain (

). Note: some members are erroneously annotated as "Phospholipase C" (plcA).
Ionotropic glutamate receptor, plant (Iontropic_Glu_rcpt_pln)
Type: Family

This group represents an ionotropic glutamate-like receptor, plant type. They have sequence similarity with animal ionotropic glutamate receptor . Interestingly, despite sharing a common structure, GLRs and iGluRs display major sequence divergences, especially in key domains such as the receptor, the pore, and the 'gate'. Electrophysiological characterization of PpGLR1, AtGLR3.2, and AtGLR3.3 showed their ligand-independent activity, providing evidence for functional differences between iGluRs and at least these specific GLRs . Animal ionotropic glutamate receptors (iGluRs) functions in the nervous system. while plant glutamate receptor-like (GLR) homologues are involved in many plant-specific physiological functions, such as sperm signaling in moss, pollen tube growth, root meristem proliferation, innate immune and wound responses .
Adaptor protein complex AP-2, alpha subunit (AP2_complex_asu)
Type: Family

Adaptor protein complex AP-2 has a role in clathrin-mediated endocytosis and intracellular transport . AP-2 links clathrin to membrane lipids and transmembrane cargoes at the vesicle budding site . It consists of two large subunits termed adaptins (alpha and beta subunits), a medium-sized one (mu), and a small one (sigma). It is thought to act in cargo selection by interaction with selection motifs encoded in the cytoplasmic tails of cargo molecules. The N-terminal domains of the adaptins, together with the mu and sigma subunits, constitute the 'head' of the adaptor, which interacts with plasma membrane lipids and cargoes. AP-2 plays a role in the recycling of synaptic vesicle membranes from the presynaptic surface .

This family represents the alpha subunit of adaptor protein complex AP-2.
Adaptor protein complex AP-3, delta subunit (AP3_complex_dsu)
Type: Family

The adaptor protein complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. Adaptor protein complex 3 (AP-3) appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles.

AP-3 is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2). The subunits of non-clathrin- and clathrin-associated adaptor protein complex 3 play a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or in endosomes.

This group represents an adaptor protein complex AP-3, delta subunit.
Coatomer gamma subunit (Coatomer_gsu)
Type: Family

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .

This group represents the coatomer gamma subunit.
Adaptor protein complex AP-1, gamma subunit (AP1_complex_gsu)
Type: Family

The adaptor protein complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules . Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Subunits of clathrin-associated adaptor protein complex 1 play a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or in endosomes.

This group represents an adaptor protein complex AP-1, gamma subunit.
Adaptor protein complex AP-4, epsilon subunit (AP4_complex_esu)
Type: Family

Adapter-like complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). It is a subunit of a novel type of clathrin-or non-clathrin-associated protein coat involved in targeting proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system .

This group represents an adaptor protein complex AP-4, epsilon subunit.
Stonin (Stonin)
Type: Family

This entry includes invertebrate stoned-B and its vertebrate homologues, stonins -1 and -2. Stoned-B is an adapter protein involved in endocytic recycling of synaptic vesicles membranes. It may act by mediating the retrieval of synaptotagmin protein Syt from the plasma membrane, thereby facilitating the internalization of multiple synaptic vesicles from the plasma membrane . In humans, stonin-2 may be involved in the vesicle recycling and facilitate clathrin-coated vesicle uncoating .
Histone-lysine N-methyltransferase Set1, fungi (Set1_fungi)
Type: Family

This entry represents fungal-type histone H3-K4 methyltransferase Set1 (

), which is the catalytic component of the COMPASS (Set1C) complex that specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation . The COMPASS (Set1C) complex consists of Set1(2), Bre2(2), Spp1(2), Sdc1(1), Shg1(1), Swd1(1), Swd2(1), and Swd3(1) .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Homeobox protein HXA9/HXB9/HXC9 (HXA9/HXB9/HXC9)
Type: Family

This entry includes a group of homeobox proteins, including HXA9/HXB9/HXC9 from humans. They are sequence-specific transcription factors which are involved in regulating developmental gene expression in cell lineage differentiation .
Antirestriction, ArdC (Antirestriction_ArdC)
Type: Family

The IncW plasmid pSa contains the gene ard, which encodes an antirestriction protein that is specific for type I restriction and modification systems . The protein has no significant similarities with other known Ard proteins (ArdA and ArdB types) except for the "antirestriction" motif (14 amino acid residues in length). This is conserved in all known Ard proteins. ArdC does, however, have a high degree of similarity (about 38% identity) to the N-terminal region of RP4 TraC1 primase, which includes about 300 amino acid residues and seems essential for binding to single-stranded DNA, as well as TraC1 transport to the recipient cells during the transfer of plasmid DNA. ArdC also binds to single-stranded DNA .
C2H2-type Zinc finger protein, YY1-like (YY1-like)
Type: Family

This entry represents a group of C2H2-type Zinc finger proteins, including a transcription factor yin and yang 1 (YY1). YY1 has been shown to regulate cell proliferation and differentiation, and its deficiency in mice results in peri-implantation lethality during embryonic development. It has also been linked to cancers .

Proteins in this entry also include YY2. It may antagonize YY1 and function in development and differentiation .
Tellurite resistance, TerA (Tellurite_resistance_TerA)
Type: Family

This group represents a tellurite resistance protein TerA.
Signal transduction histidine kinase, PgtB (Sig_transdc_His_kinase_PgtB)
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 PgtB. PtgB is a member of the two-component regulatory system pgtB/pgtA that regulates the inducible phosphoglycerate transport system, where is activates pgtA (RR) by phosphorylation.
Ribonuclease Nob1, eukaryote (Nob1_euk)
Type: Family

Budding yeast Nob1 is involved in proteasomal and 40S ribosomal subunit biogenesis. It is required for cleavage of the 20S pre-rRNA to generate the mature 18S rRNA .
Peptidase S1A, matriptase-2 (Pept_S1A_matriptase-2)
Type: Family

This entry contains serine peptidases belonging to MEROPS petidase family S1A (clan PA(S)), members are annotated as matriptase-2. Matriptase-2 is a type II transmembrane serine peptidase that plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels .
SET domain containing methyltransferase Efm1/Rkm1 (Efm1/Rkm1)
Type: Family

This entry represents a group of yeast lysine methyltransferases, including Efm1 and Rkm1. They are S-adenosylmethionine-dependent lysine methyltransferases. Rkm1 monomethylates ribosomal protein S18 (RPS18A and RPS18B) at 'Lys-48' and dimethylates ribosomal protein L23 (RPL23A and RPL23B) at 'Lys-106' and 'Lys-110' . Efm1 monomethylates elongation factor 1-alpha (TEF1/TEF2) at 'Lys-30' .
Bifunctional 3-hexulose-6-phosphate synthase/demethylmenaquinone methyltransferase, predicted (Bifunct_HPS/DMK_prd)
Type: Family

This group represents a predicted bifunctional 3-hexulose-6-phosphate synthase/demethylmenaquinone methyltransferase.