SII-SWORD/CoKE huggingface dataset:
CLU domain containing protein (CLU_prot)
Type: Family

This entry includes protein clueless from Drosophila, Clu1 from yeasts and protein CLU from plants. They are involved in proper cytoplasmic distribution of mitochondria .

Protein clueless from Drosophila is required for mitochondrial subcellular localisation, interacts genetically with parkin . It is highly expressed in larval neuroblasts, affects mitochondrial localisation and suppresses mitochondrial oxidative damage .

Budding yeast Clu1 is a subunit of the eukaryotic translation initiation factor 3 (eIF3). It can influence mitochondrial morphology and distribution .
Eukaryotic translation initiation factor 3 subunit H (eIF3h)
Type: Family

Eukaryotic translation initiation factor 3 subunit H (eIF3h) is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome . It is a non-peptidase homologue in peptidase family M67 (MEROPS identifier M67.971).

Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells .
Eukaryotic translation initiation factor 3 subunit I (eIF3i)
Type: Family

Eukaryotic translation initiation factor 3 subunit I is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome . The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression .
Lipoyl synthase, chloroplastic (Lipoyl_synth_chlpt)
Type: Family

Lipoyl synthase is an iron-sulphur protein . It is localised to mitochondria in yeast and Arabidopsis . It generates lipoic acid, a thiol antioxidant that is linked to a specific Lys as prosthetic group for the pyruvate and alpha-ketoglutarate dehydrogenase complexes and the glycine-cleavage system.

This entry represents lipoyl synthase from plant chloroplasts.
Lipoyl synthase, mitochondrial (Lipoyl_synth_mt)
Type: Family

Lipoyl synthase is an iron-sulphur protein . It is localised to mitochondria in yeast and Arabidopsis . It generates lipoic acid, a thiol antioxidant that is linked to a specific Lys as prosthetic group for the pyruvate and alpha-ketoglutarate dehydrogenase complexes and the glycine-cleavage system.

This entry represents lipoyl synthase from plant mitochondria.
Eukaryotic translation initiation factor 3 subunit M (eIF3m)
Type: Family

This entry represents the eukaryotic translation initiation factor 3 subunit M (eIF3m) and the COP9/Signalosome and eIF3 complex-shared subunit 1 (CIF-1) from roundworms. eIF3m is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome .
Adenylosuccinate synthetase isozyme 2, chordates (AdSS_2_vert)
Type: Family

This entry represents the adenylosuccinate synthetase isozyme 2 (AdSS2) (

) from vertebrates. It is a component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. It catalyses the first committed step in the biosynthesis of AMP from IMP .
Eukaryotic translation initiation factor 3 subunit F (eIF3f)
Type: Family

Eukaryotic translation initiation factor 3 subunit F is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome . In humans, it exhibits a deubiquitinase activity regulating Notch activation .
Mitochondrial distribution and morphology protein 12 (Mdm12)
Type: Family

Mitochondrial distribution and morphology protein 12 (Mdm12) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. Mdm12 is required for the interaction of the ER-resident membrane protein Mmm1 and the outer mitochondrial membrane-resident β-barrel protein Mdm10 . The Mdm12-Mmm1 subcomplex functions in the biogenesis of all mitochondrial outer membrane β-barrel proteins, and acts in a late step after the SAM (sorting and assembly machinery) complex. The Mdm10-Mdm12-Mmm1 subcomplex further acts in the Tom40 (translocase of outer membrane 40)-specific pathway after the action of the Mdm12-Mmm1 complex. Mdm12 is essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids .
Very-long-chain 3-oxoacyl-CoA reductase, fungal (3_ketoreductase_fungal)
Type: Family

Very-long-chain 3-oxoacyl-CoA reductase (

) is a component of the microsomal membrane bound fatty acid elongation system, which produces the 26-carbon very long-chain fatty acids (VLCFA) from palmitate. It catalyses the reduction of the 3-ketoacyl-CoA intermediate that is formed in each cycle of fatty acid elongation. VLCFAs serve as precursors for ceramide and sphingolipids .
Large ribosomal subunit protein P1/P2 (Ribosomal_P1/P2)
Type: Family

This entry includes eukaryotic 60S acidic ribosomal protein P1/P2 , as well as archaeal P1 (also known as 50S ribosomal protein L12). These proteins play an important role in the elongation step of protein synthesis .

Archaeal L12 is functionally equivalent to L7/L12 in bacteria and the P1 and P2 proteins in eukaryotes. L12 is homologous to P1 and P2 but is not homologous to bacterial L7/L12. It is located in the L12 stalk, with proteins L10, L11, and 23S rRNA. In several mesophilic and thermophilic archaeal species, the binding of 23S rRNA to protein L11 and to the L10/L12p pentameric complex was found to be temperature-dependent and cooperative .

Eukaryotic P1 and P2 are functionally equivalent to the bacterial protein L7/L12, but are not homologous to L7/L12. P2 is located in the L12 stalk, with proteins P1, P0, L11, and 28S rRNA. P1 and P2 are the only proteins in the ribosome to occur as multimers, always appearing as sets of heterodimers. Eukaryotes have four copies (two heterodimers), while most archaeal species contain six copies of L12p (three homodimers). Bacteria may have four or six copies of L7/L12 (two or three homodimers) depending on the species . Experiments using S. cerevisiae P1 and P2 indicate that P1 proteins are positioned more internally with limited reactivity in the C-terminal domains, while P2 proteins seem to be more externally located and are more likely to interact with other cellular components . In lower eukaryotes, P1 and P2 are further subdivided into P1A, P1B, P2A, and P2B, which form P1A/P2B and P1B/P2A heterodimers . Some plants have a third P-protein, called P3, which is not homologous to P1 and P 2 .

In humans, P1 and P2 are strongly autoimmunogenic. They play a significant role in the etiology and pathogenesis of systemic lupus erythema (SLE). In addition, the ribosome-inactivating protein trichosanthin (TCS) interacts with human P0, P1, and P2, with its primary binding site in the C-terminal region of P2. TCS inactivates the ribosome by depurinating a specific adenine in the sarcin-ricin loop of 28S rRNA .
Sulfate adenylyltransferase (Sulf_adenylyltr_euk)
Type: Family

Sulfate adenylyltransferase (

) catalyses the first intracellular reaction of sulfate assimilation, forming adenosine-5'-phosphosulfate (APS) from inorganic sulfate and ATP. It plays an important role in sulfate activation as a component of the biosynthesis pathway of sulfur-containing amino acids . It is often found as a fusion protein with adenylylsulphate kinase.
Mitochondrial distribution and morphology protein 34 (Mdm34)
Type: Family

Mitochondrial distribution and morphology protein 34 (Mdm34) is a component of the ERMES/MDM complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. MDM34 is required for the interaction of the ER-resident membrane protein MMM1 and the outer mitochondrial membrane-resident β-barrel protein MDM10 .
Maintenance of mitochondrial morphology protein 1 (Mmm1)
Type: Family

Maintenance of mitochondrial morphology protein 1 (Mmm1) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. The MDM12-MMM1 subcomplex functions in biogenesis of all outer membrane β-barrel proteins, and acts in a late step after the SAM (sorting and assembly machinery) complex . The MDM10-MDM12-MMM1 subcomplex further acts in the TOM40 (translocase of outer membrane 40)-specific pathway after the action of the MDM12-MMM1 complex .
Get 1, fungi (Get1_fungi)
Type: Family

The Golgi to ER traffic (GET) complex is composed of Get1, Get2 and Get3. The complex is involved in the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum . Get1 and Get2 form a transmembrane complex and interact with Get3, an ATPase which recognises and selectively binds the transmembrane domain of TA proteins in the cytosol .
Mitochondrial distribution and morphology protein 10 (Mdm10)
Type: Family

Mitochondrial distribution and morphology protein 10 (Mdm10) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. MDM10 is involved in the late assembly steps of the general translocase of the mitochondrial outer membrane (TOM complex) . It functions in the TOM40-specific route of the assembly of outer membrane β-barrel proteins, including the association of TOM40 with the receptor TOM22 and small TOM proteins .
Ubiquinone biosynthesis protein Coq4, eukaryotic (Coq4_euk)
Type: Family

Ubiquinone biosynthesis protein Coq4 is a component of a multi-subunit COQ enzyme complex (composed of at least Coq3, Coq4, Coq5, Coq6, Coq7 and Coq9), which plays a role in the coenzyme Q (ubiquinone) biosynthetic pathway . Coq4 plays an essential role in organising the COQ enzyme complex and is required for steady-state levels of Coq3, Coq6, Coq7 and Coq9 . This entry represents eukaryotic Coq4.
Arsenical pump-driving ATPase (Ars_ATPase)
Type: Family

Active extrusion is a common mechanism for the detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. This is particularly important for arsenic extrusion because of its prevalence in the environment and its potential to cause health and environmental problems. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. This entry represents a family of arsenical pump-driving ATPases.
Arsenical pump ATPase, ArsA/GET3, eukaryotic (ATPase_ArsA/GET3_euk)
Type: Family

This entry represents the eukaryotic branch of the ArsA/GET3 family.

Active extrusion is a common mechanism for the detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. This is particularly important for arsenic extrusion because of its prevalence in the environment and its potential to cause health and environmental problems. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. ArsA from Escherichia coli is the catalytic subunit of the ArsAB extrusion pump, providing resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). Maintenance of a low intracellular concentration of oxidation produces resistance to the toxic agents. A third protein, ArsC, expands the substrate specificity to allow for arsenate resistance. ArsC reduces arsenate to arsenite, which is subsequently pumped out of the cell . ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids to the pump stimulates the ATPase activity .

Homologues of the bacterial ArsA ATPase are found in eukaryotes, where they have several recognised functions unrelated to arsenic resistance . Caenorhabditis elegans homologue Asna-1 is required for defence against arsenite and antimonite toxicity , and may be also involved in insulin signaling . The homologue in yeast, GET3/Arr4, is part of the GET complex and not only is involved in stress tolerance to metals and heat , but also specifically recognises transmenbrane domains of tail-anchored (TA) proteins destined for the secretory pathway . Archaeal GET3 homologues have also been discovered, suggesting that that archaea may possess a TA protein targeting pathway similar to that in eukaryotes .
Lon protease, bacterial (Lon_bac)
Type: Family

Lon protease belongs to the S16 peptidase family and is an ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins, as well as certain short-lived regulatory proteins. It is required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress . In pathogenic bacteria, it is required for the expression of virulence genes that promote cell infection .

Lon (La) protease was the first ATP-dependent protease to be purified from
E. coli . The enzyme is a homotetramer of 87kDa subunits, with one proteolytic and one ATP-binding site per monomer, making it structurally less complex than other known ATP-dependent proteases . Despite this relative structural simplicity, Lon recognises its substrates directly, without delegating the task of substrate recognition to other enzymes .

This entry represents a subfamily of bacterial lon proteases.
Shikimate kinase 2 (Shikimate_kinase_2)
Type: Family

Shikimate kinase 2 (

) catalyses the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate .
Kynurenine 3-monooxygenase (Kynurenine_monooxygenase)
Type: Family

Kynurenine 3-monooxygenase (also known as kynurenine 3-hydroxylase) catalyses the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). It has a key role in tryptophan catabolism and is required for synthesis of quinolinic acid, a neurotoxic NMDA (N-methyl-D-aspartate) receptor antagonist .
Sirtuin, class III (Sirtuin_class_III)
Type: Family

This entry represents the Sirtuin family, class III subfamily. Proteins in this subfamily include the NAD-dependent protein deacylase sirtuin-5. Sirtuin-5 is the NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins .

The sirtuin (also known as Sir2) family is broadly conserved from bacteria to human. Yeast Sir2 (silent mating-type information regulation 2),
the founding member, was first isolated as part of the SIR complex required for maintaining a modified chromatin structure at telomeres. Sir2 functions
in transcriptional silencing, cell cycle progression, and chromosome stability . Although most sirtuins in eukaryotic cells are located in the nucleus, others are cytoplasmic or mitochondrial.

This family is divided into five classes (I-IV and U) on the basis of a phylogenetic analysis of 60 sirtuins from a wide array of organisms . Class I and class IV are further divided into three and two subgroups, respectively. The U-class sirtuins are found only in Gram-positive bacteria . The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) . The human genome encodes seven sirtuins, with representatives from classes I-IV .

Sirtuins are responsible for a newly classified chemical reaction, NAD-dependent protein deacetylation. The final products of the reaction are the
deacetylated peptide and an acetyl ADP-ribose . In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines .

Sirtuins typically consist of two optional and highly variable N- and C-terminal domain (50-300 aa) and a conserved catalytic core domain (~250 aa). Mutagenesis experiments suggest that the N- and C-terminal regions help direct catalytic core domain to different targets .

The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains .
Small ribosomal subunit protein eS19, archaeal (Ribosomal_eS19_archaeal)
Type: Family

This entry represents the small ribosomal subunit protein eS19, also known as archaeal ribosomal protein S19e. It may be involved in maturation of the 30S ribosomal subunit.

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 .
Arginine decarboxylase proenzyme (ArgDC)
Type: Family

Arginine decarboxylase proenzyme specifically catalyses the decarboxylation of L-arginine to agmatine. Although this family evolved from an S-adenosylmethionine decarboxylase (AdoMetDC), it has no AdoMetDC activity .
MSEP-CTERM protein (MSEP-CTERM)
Type: Family

Members of this protein family average over 900 residues in length and appear to have multiple membrane-spanning helices in the N-terminal half. The extreme C-terminal region consists of a motif with consensus sequence MSEP, then a transmembrane α helix, then a short region with several basic residues. This region, hereby dubbed MSEP-CTERM, resembles other putative sorting signals associated with the archaeosortase/exosortase protein family (see

). Genes for all members of this family are found next to a gene for exosortase K.
Exosortase K (Exosort_XrtK)
Type: Family

Members of this protein family are exosortase K, a bacterial branch of the archaeosortase/exosortase family of protein-processing enzymes (see

).
CGP-CTERM protein-sorting domain (CGP_CTERM)
Type: Domain

This domain has an essentially invariant motif, Cys-Gly-Pro, followed by a highly hydrophobic transmembrane domain, always at the protein C terminus. It occurs, so far, strictly in the family Thermococcaceae (including Thermococcus and Pyrococcus) within the Euryarchaeota. It occurs in ten proteins per genome on average, and proteins with the domain may lack similarity elsewhere. The presumed sorting/processing protein, for which this domain contains the recognition sequence is unknown, but it is unlikely to be a member of the exosortase/archaeosortase family. The Cys residue suggests a lipid modification. Upstream from this domain, most member proteins have an extremely Thr-rich sequence, suggesting archaeal surface protein O-linked glycosylation.
Eight-cysteine-cluster domain (Heavy_Cys)
Type: Domain

In this domain of about 50 residues, eight of twelve invariant residues are Cys. Proteins with this domain tend to have N-terminal signal sequences, suggesting an extracytoplasmic location for this domain.
Methyltransferase, Rta_06860 family (Meth_Rta_06860)
Type: Family

Members of this family are methyltransferases that mark a widely distributed large conserved gene neighbourhood of unknown function. It appears most common in soil and rhizosphere bacteria.
tRNA (Mo5U34)-methyltransferase-like (Mo5U34_MeTrfas-like)
Type: Family

Proteins in this entry include bacterial tRNA U34 carboxymethyltransferases and some methyltransferases from soil and rhizosphere bacteria. tRNA U34 carboxymethyltransferase ComB catalyses the conversion of 5-hydroxyuridine (ho5U) to uridine-5-oxyacetic acid (cmo5U) at the wobble position (34) of tRNA . cmo5U is a modified nucleoside that is apparently necessary for the efficient decoding of G-ending Pro, Ala, and Val codons in these organisms .
CGP-CTERM domain protein (Heavy_Cys_CGP)
Type: Family

Members of this protein family are restricted to the Pyrococcus and Thermococcus genera of the archaea. Member proteins have a C-terminal, Cys-containing predicted surface anchor domain, where the Cys may be the site of cleavage and lipid attachment (see domain

). Members also contain a region crowded with 10 invariant Cys in 60 residues (see domain

), possible ligands to some redox cofactor.
Archaeosortase ArtF (Archaeo_ArtF)
Type: Family

Members of this protein family, ArtF, belong to the archaeosortase/exosortase family, in which many members associate with specific protein C-terminal putative protein sorting domains (exosortase A with PEP-CTERM, archaeosortase A with PGF-CTERM, etc). This subgroup is observed in Thermococcus gammatolerans EJ3 and Thermococcus sp. AM4, but the gene neighbourhood is not conserved. The cognate sequence to ArtF is unknown, but should not be ICGP-CTERM (

), found also in many Pyrococcus species that lack any archaeosortase family member.
Prepilin-type processing-associated H-X9-DG C-terminal domain (Pre_pil_HX9DG_C)
Type: Domain

This entry describes a region of approximately 16 residues found typically about 30 residues away from the C terminus of large numbers of proteins in the Planctomycetes, Lentisphaerae, and Verrucomicrobia, on proteins with a prepilin-type N-terminal cleavage/methylation site (see

). The motif H-X(9)-D-G is nearly invariant. Single genomes may encode over 200 such proteins.
B12-binding domain/radical SAM domain protein, rhizo-twelve system (B12_rSAM_oligo)
Type: Family

A variety of bacteria, including multiple species of Bradyrhizobium, Mesorhizobium, and Methylobacterium, have a typically twelve-gene cassette (hence the designation rhizo-twelve) for the biosynthesis of some unknown oligosaccaride. This family is a B12-binding domain/radical SAM domain protein found in roughly half of these cassettes, but nowhere else.
PEFG-CTERM domain (PEFG-CTERM)
Type: Domain

This putative protein sorting/processing domain occurs about ten times per genome in members of the Thaumarchaeota. Its putative handling protein, a member of the archaeosortase/exosortase protein family, is exceptional in having a Ser rather than Cys at the putative active site. The highly conserved motif resembles the PEF-CTERM protein sorting domain of family

, but membership does not overlap.