SII-SWORD/CoKE huggingface dataset:
GTPase GIMA/IAN/Toc (GIMA/IAN/Toc)
Type: Family

This entry includes two subfamilies of the TRAFAC (translation factor related) class AIG1/Toc34/Toc159-like paraseptin GTPase family.

The GTPases of immunity-associated protein (GIMAP)/immune-associated nucleotide-binding protein (IAN) subfamily is conserved among vertebrates and angiosperm plants and has been postulated to regulate apoptosis, particularly in context with diseases such as cancer, diabetes, and infections. The function of GIMAP/IAN GTPases has been linked to self defense in plants and to the development of T cells in vertebrates .

Plant-specific Toc (translocon at the outer envelope membrane of chloroplasts) proteins. Toc proteins function as integral components of the chloroplast protein import machinery. The Toc translocon contains the two membrane-bound GTPases Toc33/34 and Toc 159, which expose their G domains to the cytosol that recognise and then deliver precursor proteins through the translocation pore Toc75 .
Large ribosomal subunit protein uL29, eukaryotes (Ribosomal_uL29_euk)
Type: Family

This entry includes the large ribosomal protein uL29 from eukaryotes .

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 .
Phenylalanine-tRNA ligase, class IIc, beta subunit (Phe-tRNA-ligase_IIc_bsu)
Type: Family

Phenylalanine-tRNA ligase (

) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as beta (E. coli) or alpha subunit (see

). Reciprocally the large subunit (pheT gene) can be designated as alpha (E. coli) or beta. In all other kingdoms the two subunits have equivalent length in eukaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an alpha2 beta2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanine-tRNA ligase as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other ligases .

This family describes the beta subunit. The beta subunits break into two subfamilies that are considerably different in sequence, length, and pattern of gaps. This family includes both subfamilies.
Tubulin-like protein FtsZ/CetZ (FtsZ/CetZ)
Type: Family

This entry represents the tubulin-like proteins FtsZ and CetZ. FtsZ is a homologue of eukaryotic tubulin and is essential in the process of cell division; it forms a contractile ring structure (Z ring) at the future cell division site. The regulation of the ring assembly controls the timing and the location of cell division. One of the functions of the FtsZ ring is to recruit other cell division proteins to the septum to produce a new cell wall between the dividing cells .

Homologous from plants, such as AtFtsZ2-1, AtFtsZ1 and AtFtsZ2-2 are components of the plastid division machinery that forms a contractile ring at the division site and are required for plastid division in a dose-dependent manner . Cetz, an archaeal tubulin-like protein related to tubulin and FtsZ, was initially annotated as FtsZ3 or FtsZ type 2, does not affect cell division, instead, it is involved in cell shape control, required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that is essential for normal swimming motility . CetZ co-exists with FtsZ in many archaea. These proteins contain a GTPase domain that binds and hydrolyses GTP.
Cytochrome c-type biogenesis protein CcsA/CcmC (Cyt_c_biogenesis_CcsA/CcmC)
Type: Family

This family represents proteins involved in cytochrome c assembly in mitochondria, chloroplast and bacteria; including CcmC from Escherichia coli and CcsA from Chlamydomonas . CcsA is called ResC in Bacillus (where there is additional N-terminal sequence) , while chloroplast proteins are consistently named CcsA.

CcmC interacts directly with heme, and it is the only protein of the ccm operon that is strictly required for heme transfer . CcsA is required during biogenesis of c-type cytochromes at the step of heme attachment .
Dynamin, N-terminal (Dynamin_N)
Type: Domain

This entry represents the N-terminal domain found in dynamins.

Membrane transport between compartments in eukaryotic cells requires proteins that allow the budding and scission of nascent cargo vesicles from one compartment and their targeting and fusion with another. Dynamins are large GTPases that belong to a protein superfamily that, in eukaryotic cells, includes classical dynamins, dynamin-like proteins, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins , and are involved in the scission of a wide range of vesicles and organelles. They play a role in many processes including budding of transport vesicles, division of organelles, cytokinesis and pathogen resistance.

The minimal distinguishing architectural features that are common to all dynamins and are distinct from other GTPases are the structure of the large GTPase domain (300 amino acids) and the presence of two additional domains; the middle domain and the GTPase effector domain (GED), which are involved in oligomerization and regulation of the GTPase activity.
Reticulon-like (Reticulon-like)
Type: Family

This entry represents reticulon-like proteins from plants, including RTNLB1-16 from Arabidopsis. They are involved in Agrobacterium infection and VirB2 peptide-induced plant defense response . It also includes RTN1 from S. cerevisiae.

Eukaryotic proteins of the reticulon (RTN) family all share an association with the endoplasmic reticulum (ER). Whereas amino-terminal regions are not related to one another, all reticulon proteins share a 200 amino acid residue region of sequence similarity at the C-terminal. This region contains two large hydrophobic regions separated by a 66 residue hydrophilic segment. The conserved hydrophobic C-terminal portion has been shown to play an essential role in the association of reticulons with the ER membrane. The hydrophobic portions are supposed to be membrane-embedded and the hydrophilic 66 residue localized to the lumenal/extracellular face of the membrane. Most reticulons have a di-lysine ER retention motif at the C-terminal. Because of their likely association with the rough as well as the smooth ER, the reticulons might play some role in transport processes or in regulation of intracellular calcium levels. It has been suggested that the reticulons may be serving as ER-associated channel-like complexes .
Exportin-1/5 (XPO1/5)
Type: Family

This entry includes exportin-1/5 from eukaryotes.

Exportin-1, also known as CRM1, is a nuclear export receptor that have been shown to be involved in U3 snoRNA transport from Cajal bodies to nucleoli . It also controls the composition of many nucleoplasmic complexes .

Exportin-5 mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos) . Exportin-5 yeast homologue, also known as Msn5, is involved in nuclear import of replication protein A and export of Far1 and transcription factors Swi5, Swi6, Msn2, and Pho4 . Its Arabidopsis homologue, HASTY 1, is involved in the nuclear export of microRNAs (miRNAs) .
Beta carbonic anhydrases, cladeB (Beta_CA_cladeB)
Type: Family

Carbonic anhydrases (CA) are zinc-containing enzymes that catalyse the reversible hydration of carbon dioxide in a two-step mechanism in which the nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide is followed by the regeneration of an active site by ionization of the zinc-bound water molecule and removal of a proton from the active site. CAs are ubiquitous enzymes involved in fundamental processes like photosynthesis, respiration, pH homeostasis and ion transport. There are three evolutionarily distinct families of CAs (the alpha-, beta-, and gamma-CAs) which show no significant sequence identity or structural similarity. Within the beta-CA family there are four evolutionarily distinct clades (A through D) .

This entry represents the cladeB of the beta-CA family. Proteins in this entry are mostly from plants and bacteria, including BCA1-6 from Arabidopsis and CynT from E. coli. BCA1 and BCA4 have been shown to acts as upstream regulators of CO2-controlled stomatal movements in guard cells . CynT catalyses the hydration of carbon dioxide and thus prevents depletion of cellular bicarbonate .
Wee1-like protein kinase, catalytic domain (PKc_Wee1-like)
Type: Domain

PKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This entry includes Wee1 from Arabidopsis. Wee1 is a cell cycle checkpoint kinase that is involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis . It has been shown that Arabidopsis Wee1 directly interacts with and phosphorylates the E3 ubiquitin ligase FBL17 that promotes the degradation of CDK inhibitors .
BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 1-3 (BACURD1-3)
Type: Family

This entry represents a group of BTB/POZ domain-containing proteins, such as BACURD1-3 from humans. They act as the substrate-specific adapters of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of RhoA, leading to its degradation by the proteasome . This entry also includes EAP3 from Arabidopsis. The BTB/POZ domain of EAP3 displays poor conservation of the residues required for CUL3 binding and is not likely to function as an E3 ligase adaptor .
Multidrug and toxic compound extrusion family, eukaryotic (MATE_euk)
Type: Family

The integral membrane proteins from the MATE family are involved in exporting metabolites across the cell membrane and are responsible for multidrug resistance (MDR) in many bacteria and animals. MATE has also been identified as a large multigene family in plants, where the proteins are linked to disease resistance. A number of family members are involved in the synthesis of peptidoglycan components in bacteria .

This subfamily, which is restricted to eukaryotes, contains vertebrate solute transporters responsible for secretion of cationic drugs across the brush border membranes, yeast proteins located in the vacuole membrane, and plant proteins involved in disease resistance and iron homeostatis under osmotic stress .
Multidrug and toxic compound extrusion MepA-like (MATE_MepA-like)
Type: Family

The integral membrane proteins from the MATE family are involved in exporting metabolites across the cell membrane and are responsible for multidrug resistance (MDR) in many bacteria and animals. MATE has also been identified as a large multigene family in plants, where the proteins are linked to disease resistance. A number of family members are involved in the synthesis of peptidoglycan components in bacteria .

This subfamily includes Streptococcus aureus MepA. It may function as a multidrug efflux pump .
KH domain-containing BBP-like (BBP-like)
Type: Family

This entry represents a group of KH domain-containing proteins that share protein sequence similarity with fungal BBP protein, such as KH domain-containing RNA-binding protein QKI and KHDR1-3 from human. QKI is a RNA-binding protein that plays a central role in myelination and regulates pre-mRNA splicing, mRNA export and protein translation .

BBP/SF1 family members include the branchpoint binding proteins (BBP) from yeast and their mammalian homologue, splicing factor 1 (SF1). They are KH domain containing proteins required for pre-spliceosome formation, which is the first step of pre-mRNA splicing . In budding yeasts, BBP binds the conserved RNA sequence UACUAAC, called the branchpoint motif, found near the 3' end of yeast introns . Besides its function in pre-mRNA splicing, BBP is also involved in nuclear retention of pre-mRNA . Mammalian SF1, also known as ZFM1, may act as transcription repressor .
MKRN-like (MKRN-like)
Type: Family

The MKRN protein family includes the ribonucleoproteins that are characterised by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity . At least four makorin genes exist in vertebrates .

Makorin-3 is an E3 ubiquitin ligase that catalyses the covalent attachment of ubiquitin moieties onto substrate proteins. it acts as a key developmental timer that helps ensure puberty begins at the appropriate age, by inhibiting premature activation of the reproductive hormone cascade. Epigenetically regulates GNRH1 transcription by disrupting the binding of methyl-DNA binding protein 3/MBD3 to the promoter of GNRH1. Mechanistically, mediates the non-proteolytic ubiquitination of MBD3 at multiple sites with 'Lys27' ubiquitin linkages and thereby regulates the methylation status of the genome, including GNRH1 promoter . It modulates the stability and translation of GNRH1 mRNA by mediating the non-proteolytic ubiquitination of PABP family members PABPC1, PABPC3 and PABPC4 at multiple sites. It also participates also in the maintenance of genomic and epigenomic stability by regulating the abundance of APEX2 via 'Lys-48'-linked ubiquitination .
Glutathione S-transferase Omega/Tau-like (Omega/Tau-like)
Type: Family

This entry represents a group of cytosolic GSTs, including Omega and Tau family members. Proteins in this family are known to catalyse the following reaction types: conjugate addition, dehydroascorbate reductase, disulfide bond reductase, nucleophilic addition, nucleophilic aromatic substitution, nucleophilic substitution (SN2), peroxidase, and thiolysis reactions. For example, protein sepia (

) has experimentally-confirmed pyrimidodiazepine synthase activity with 6-pyruvoyltetrahydropterin, which is a reaction involved in eye pigment synthesis in Drosophila. Additionally, it has experimentally-confirmed dehydroascorbate reductase activity and disulfide bond reductase activity with beta-hydroxyethylene disulfide .
Glutathione S-transferases Tau, C-terminal alpha-helical domain, plant (GST_C_Tau)
Type: Domain

The plant-specific class Tau GST has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones .
Pre-mRNA-splicing factor Syf1-like (Syf1-like)
Type: Family

This entry represents a group of pre-mRNA-processing factors, including Syf1/Clf1 from budding yeasts and protein crooked neck (CRN) from fruit flies. Syf1 acts as a component of the NTC complex (or Prp19-associated complex), associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation . Clf1 is a splicing factor that are part of at least two multisubunit protein complexes, a small nuclear RNA-free structure similar to what was reported as the Prp19 complex and an RNP structure that contains the U2, U5, and U6 small nuclear RNAs . Human CRN-like protein is also implicated in pre-mRNA splicing . The crn mutation in Drosophila has been shown to cause abnormalities in the central and peripheral nervous systems .
DNA mismatch repair MutS (MutS)
Type: Family

Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication . MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base . MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch . MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level . Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA.
Large ribosomal subunit protein uL3, archaeal/eukaryotic-type (L3_arc_euk)
Type: Family

This entry represents archaeal and eukaryotic L3 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 .
Sulfurtransferase TST/MPST-like (TST/MPST-like)
Type: Family

This entry represents a group of sulfurtransferases, including thiosulfate sulfurtransferases and 3-mercaptopyruvate sulfurtransferases.

Thiosulfate sulfurtransferase (also known as rhodanese,

) is an enzyme which catalyses the transfer of the sulphane atom of thiosulphate to cyanide, to form sulphite and thiocyanate. In vertebrates, rhodanese is a mitochondrial enzyme that is involved in forming iron-sulphur complexes and cyanide detoxification. A cysteine residue takes part in the catalytic mechanism . Some bacterial proteins may also express sulfotransferase activity. These include, SseA from Mycobacterium leprae and Escherichia coli, Azotobacter vinelandii rhdA, Saccharopolyspora erythraea cysA and Synechococcus sp. (strain PCC 7942) rhdA .

3-Mercaptopyruvate sulfurtransferase (MPST,

catalyses the desulfuration of 3-mercaptopyruvate to generate an enzyme-bound hydropersulfide .
Oxoprolinase-like (Oxoprolinase-like)
Type: Family

Oxoprolinase family consists of oxoprolinase, hydantoinase A (HyuA) and hydantoinase B (HyuB).

Hydantoinase A (HyuA) and oxoprolinase (

) catalyse reactions involving the hydrolysis of 5-membered rings via hydrolysis of their internal imide bonds . This entry also includes (4-{4-[2-(gamma-L-glutamylamino)ethyl]phenoxymethyl}furan-2-yl)methanamine synthase from Methanocaldococcus jannaschii, which is involved in methanofuran biosynthesis, catalysing the condensation between 5-(aminomethyl)-3-furanmethanol diphosphate and gamma-glutamyltyramine to produce 4-[N-(gamma-L-glutamyl)-p-(beta-aminoethyl)phenoxymethyl]-(aminomethyl)furan (APMF-Glu) . D-5-(2-methylthioethyl)hydantoin amidohydrolase (HyuA) from Pseudomonas is a component of the hydantoinase process, an enzymatic cascade converting D-5-(2-methylthioethyl)hydantoin to N-carbamoyl-D-methionine .

This entry also includes ccetone carboxylase beta subunit and acetophenone carboxylase alpha/delta/gamma subunits. Caprolactamase subunits alpha and beta are also included in this entry, which are components of a caprolactamase involved in the degradation of caprolactam, an industrial compound mainly used in the production of Nylon 6 . They catalyse the ATP-dependent hydrolysis of the caprolactam ring to form 6-aminocaproic acid (6-ACA) . The alpha subunit is responsible for ATP-dependent substrate phosphorylation, while the beta subunit is responsible for hydrolytic lactam ring opening .