SII-SWORD/CoKE huggingface dataset:
CobE/GbiG C-terminal domain (CobE/GbiG_C)
Type: Domain

Cobalt-precorrin-5A hydrolase CbiG is specific for anaerobic cobalamin (vitamin B12) biosynthesis. CbiG, which shows homology with CobE of the aerobic pathway, participates in the conversion of cobalt-precorrin 5 into cobalt-precorrin 6 . CbiG is responsible for the opening of the delta-lactone ring and extrusion of the C2-unit . The aerobic pathway uses molecular oxygen to trigger the events at C-20 leading to contraction and expulsion of the C2-unit as acetic acid from a metal-free intermediate, whereas the anaerobic route involves the internal delivery of oxygen from a carboxylic acid terminus to C-20 followed by extrusion of the C2-unit as acetaldehyde, using cobalt complexes as substrates .

This entry represents a domain found at the C terminus of CibG. CobE is composed solely of this domain.
Metal transport protein CbiM/NikMN (CbiM/NikMN)
Type: Family

This entry represents the integral membrane protein CbiM, which forms part of the energy-coupling factor (ECF) transporter complex CbiMNOQ that is involved in cobalt import , and plays a role in the cobalamin synthesis pathway. CbiM is the substrate-specific component of the complex and is a seven-transmembrane protein . This entry also includes related proteins, such as NikMN, which may be involved in nickel transport . The CbiMNQO and NikMNQO systems form part of the coenzyme B12 biosynthesis pathway .
Uncharacterised protein family UPF0058 (UPF0058)
Type: Family

These archaebacterial proteins have no known function. Members of the family are about 90-105 amino acid residues long.
DNA primase, small subunit (DNA_primase_S)
Type: Family

DNA primase synthesises the RNA primers for the Okazaki fragments in lagging strand DNA synthesis. DNA primase is a heterodimer of large and small subunits .

This family represents the small subunit, and also includes baculovirus late expression factor 1 or LEF-1 proteins. Baculovirus LEF-1 is a DNA primase enzyme .
4-[[4-(2-aminoethyl)phenoxy]-methyl]-2-furanmethanamine-glutamate synthase (MfnF)
Type: Family

MfnF is a enzyme of the in the methanofuran biosynthetic pathway. It catalyses the coupling of F1-PP with gamma-glutamyltyramine to form APMF-Glu, the methanofuran core structure . MfnF exhibits a distinctive α/β two-layer sandwich structure that is different from the enzymes catalysing similar reactions.
Na+/H+ antiporter subunit E (Cation_antiport_E)
Type: Family

This family contains both characterised and uncharacterised bacterial and archaeal proteins; some of which are possibly transmembrane proteins involved in Na
+
/H
+
or K
+
/H
+
transport.

The characterised proteins are mnhE (Staphylococcus aureus) and PhaE (Rhizobium meliloti), which are subunits of the Na
+
/H
+
or K
+
/H
+
antiporters, that are required for sodium and potassium excretion, respectively .
RNase P subunit Pop5/Rpp14/Rnp2-like (Pop5/Rpp14/Rnp2-like)
Type: Family

This entry contains ribonuclease P (Rnp) proteins from eukaryotes and archaea. Rnp is a ubiquitous ribozyme that catalyzes a Mg2 -dependent hydrolysis to remove the 5'-leader sequence of precursor tRNA (pre-tRNA) . Archaeal and eukaryotic RNase P consist of a single RNA and archaeal RNase P has four or five proteins, while eukaryotic RNase P consists of 9 or 10 proteins. Eukaryotic and archaeal RNase P RNAs cooperatively function with protein subunits in catalysis .

Human RNase P is composed of a singular protein Pop1 and three subcomplexes, the Rpp20-Rpp25 heterodimer, Pop5-Rpp14-(Rpp30)2-Rpp40 heteropentamer, and Rpp21-Rpp29-Rpp38 heterotrimer. Although both Pop5 and Rpp14 have similar protein structure, they share a very limited sequence similarity. Moreover, the C-terminal fragments after the conserved β sheets in Pop5 and Rpp14 exhibit distinct structural features that mediate interactions with Pop1 and Rpp40, respectively .

In the hyperthermophilic archaeon Pyrococcus horikoshii OT3, RNase P is composed of the RNase P RNA (pRNA) and five proteins (PhoPop5, PhoRpp38, PhoRpp21, PhoRpp29, and PhoRpp30) .

Proteins in this entry include Rnp2 (also known as Pop5) from archaea and Pop5/Rpp14 from humans .
Putative O-antigen polymerase (O_anti_polymase)
Type: Family

This entry includes a group of archaebacterial proteins of unknown function. Members of this family may be transmembrane proteins. These are potentially O-antigen assembly enzymes, with up to 11 transmembrane regions.
Diphthamide synthase domain (Diphthami_syn_dom)
Type: Domain

Diphthamide_syn, diphthamide synthase, catalyses the last amidation step of diphthamide biosynthesis using ammonium and ATP . Diphthamide synthase is evolutionarily conserved in eukaryotes. Diphthamide is a post-translationally modified histidine residue found on archaeal and eukaryotic translation elongation factor 2 (eEF-2) .

This domain has a strongly conserved motif SXGXDS at the N terminus .
Sirohydrochlorin cobaltochelatase CbiX-like (CbiX-like)
Type: Family

This entry represents sirohydrochlorin cobaltochelatase (also known as CbiX), which catalyses the insertion of Co2+ into sirohydrochlorin as part of the anaerobic pathway to cobalamin biosynthesis. The structure of CbiX from Archaeoglobus fulgidus consists of a central mixed β-sheet flanked by four α-helices, although it is about half the size of other Class II tetrapyrrole chelatases . The CbiX proteins found in archaea appear to be shorter than those found in eubacteria .
Protein of unknown function DUF72 (DUF72)
Type: Family

The function of this family is unknown. Aquifex aeolicus has two copies of this protein. A probable aspartyl-tRNA synthetase from Escherichia coli belongs to this group.
CRISPR-associated protein Cas7/Cst2/DevR, subtype I-a/Apern (Cas7/Cst2/DevR_sub_I-a/Apern)
Type: Family

This entry represents the Cas7/Csa2 (CRISPR/Cas subtype protein 2) family of proteins, which form a stable complex with Cas5a that binds crRNA and complementary ssDNA . This archaeal clade is a member of the DevR family, which includes the DevR protein of Myxococcus xanthus, a protein whose expression appears to be regulated through a number of means, including both location and autorepression. DevR is a key regulator of development, and mutants in DevR are incapable of fruiting body development .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Uncharacterised protein family UPF0145, YbjQ-like (UPF0145_YbjQ-like)
Type: Family

This entry represents a family of proteins from cellular organisms. Structural analysis suggest members of this group are likely to have a heavy-metal binding domain. The protein oligomerises as a pentamer .
Thiamine-binding protein (Thiamine_BP)
Type: Domain

The crystal structure of two of these members shows that this domain has a ferredoxin like fold and is likely to exists as at least homodimers. Sulphate ions are located at the dimer interfaces, which are thought to confer additional stability. Although the function of this domain remains to be identified, its structure suggests a role in protein-protein interactions possibly regulated by the binding of small-molecule ligands .
Translation initiation factor IF6 (eIF6)
Type: Family

This family includes eukaryotic translation initiation factor 6 (eIF6) as well as presumed archaeal homologues.

The assembly of 80S ribosomes requires joining of the 40S and 60S subunits, which is triggered by the formation of an initiation complex on the 40S subunit. This event is rate-limiting for translation, and depends on external stimuli and the status of the cell. Eukaryotic translation initiation factor 6 (eIF6) binds specifically to the free 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit ribosomes . Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for activated protein kinase C (PKC). RACK1 is a major component of translating ribosomes, which harbour significant amounts of PKC. Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which are reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation leads to eIF6 phosphorylation and its release, promoting 80S subunit formation. RACK1 provides a physical and functional link between PKC signalling and ribosome activation .

All members of this family have a conserved pentameric fold referred to as a β/α propeller. The eukaryotic IF6 members have a moderately conserved C-terminal extension which is not required for ribosomal binding, and may have an alternative function .
Formylmethanofuran: tetrahydromethanopterin formyltransferase Ftr, C-terminal (ForMFR_H4MPT_ForTrfase_C)
Type: Domain

Formylmethanofuran:tetrahyromethanopterin formyltransferase (Ftr) is involved in C1 metabolism in methanogenic archaea, sulphate-reducing archaea and methylotrophic bacteria. It catalyses the following reversible reaction:

N-formylmethanofuran + 5,6,7,8-tetrahydromethanopterin = methanofuran + 5-formyl-5,6,7,8-tetrahydromethanopterin

Ftr from the thermophilic methanogen Methanopyrus kandleri (optimum growth temperature 98 degrees C) is a hyperthermophilic enzyme that is absolutely dependent on the presence of lyotropic salts for activity and thermostability. The crystal structure of Ftr, determined to a reveals a homotetramer composed essentially of two dimers. Each subunit is subdivided into two tightly associated lobes both consisting of a predominantly antiparallel β sheet flanked by α helices forming an α/β sandwich structure. The approximate location of the active site was detected in a region close to the dimer interface . Ftr from the mesophilic methanogen Methanosarcina barkeri and the sulphate-reducing archaeon Archaeoglobus fulgidus have a similar structure .

In the methylotrophic bacterium Methylobacterium extorquens, Ftr interacts with three other polypeptides to form an Ftr/cyclohydrolase complex which catalyses the hydrolysis of formyl-tetrahydromethanopterin to formate during growth on C1 substrates .

This entry represents the ferredoxin-like Ftr C-terminal domain.
Multiple antibiotic resistance (MarC)-related (Multi_antbiot-R_MarC)
Type: Family

MarC is a protein that spans the plasma membrane multiple times and once was thought to be a multiple antibiotic resistance protein. The function for this family is unknown .
Glycoside hydrolase family 3 C-terminal domain (Glyco_hydro_3_C)
Type: Domain

Glycoside hydrolase family 3

comprises enzymes with a number of known activities; beta-glucosidase (

); beta-xylosidase (

); N-acetyl beta-glucosaminidase (

); glucan beta-1,3-glucosidase (

); cellodextrinase(

); exo-1,3-1,4-glucanase (

).

These enzymes are two-domain globular proteins that are N-glycosylated at three sites . This entry represents the C-terminal domain, involved in catalysis and may be involved in binding beta-glucan . It is found associated with

.
Deoxyhypusine synthase (Deoxyhypusine_synthase)
Type: Family

Eukaryotic initiation factor 5A (eIF-5A), now considered to be an elongation factor (see

), contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DS,

). The enzyme catalyses the following reaction:

Spermidine + [eIF-5A]-lysine = 1,3-diaminopropane + [eIF-5A]-deoxyhypusine

The modified version of eIF-5A, and DS, are required for eukaryotic cell proliferation . The structure is known for this enzyme in complex with its NAD
+
cofactor.
Flagellin, archaeal-type (Flagellin_arc-type)
Type: Family

This protein family represents archaeal Flagellin B1-B5 , Flagellin A-A2 and similar proteins mainly found in archaea. A group of uncharacterised bacterial sequences is also included in this group.

Archaeal motility occurs by the rotation of flagella that are different to bacterial flagella, but show similarity to bacterial type IV pili. These similarities include the multiflagellin nature of the flagellar filament, N-terminal sequence similarities, as well as the presence of homologous proteins in the two systems . Also unlike bacterial flagellins but similar to type IV pilins, archaeal flagellins are initially synthesised with a short leader peptide that is cleaved by a membrane-located peptidase . The enzyme responsible for the removal of the this leader peptide is FlaK .

Archaeal flagella are composed of a number of distinct flagellin proteins, specified by genes in two separate operons (A and B) .
DNA/RNA-binding protein Alba-like (DNA/RNA-bd_Alba-like)
Type: Domain

Members of this group include the archaeal protein Alba, eukaryotic RPP25L, Ribonucleases P/MRP protein subunit POP6 and Rpp25. The Alba domain is closely related to the RNA-binding versions of the IF3-C fold such as YhbY and IF3-C. The eukaryotic lineages of the Alba family are principally involved in RNA metabolism, suggesting that the ancestral function of the IF3-C fold was related to RNA interaction .

Alba has been shown to bind DNA and affect DNA supercoiling in a temperature dependent manner . It is regulated by acetylation (alba = acetylation lowers binding affinity) by the Sir2 protein. Alba is proposed to play a role in establishment or maintenance of chromatin architecture and thereby in transcription repression. For further information see .
Prefoldin beta-like (PFD_beta-like)
Type: Family

Prefoldin (PFD) is a chaperone that interacts exclusively with type II chaperonins, hetero-oligomers lacking an obligate co-chaperonin that are found only in eukaryotes (chaperonin-containing T-complex polypeptide-1 (CCT)) and archaea. Eukaryotic PFD is a multi-subunit complex containing six polypeptides in the molecular mass range of 14-23kDa. In archaea, on the other hand, PFD is composed of two types of subunits, two alpha and four beta. The six subunits associate to form two back-to-back up-and-down eight-stranded barrels, from which hang six coiled coils. Each subunit contributes one (beta subunits) or two (alpha subunits) β hairpin turns to the barrels. The coiled coils are formed by the N and C termini of an individual subunit. Overall, this unique arrangement resembles a jellyfish. The eukaryotic PFD hexamer is composed of six different subunits; however, these can be grouped into two alpha-like (PFD3 and -5) and four beta-like (PFD1, -2, -4, and -6) subunits based on amino acid sequence similarity with their archaeal counterparts. Eukaryotic PFD has a six-legged structure similar to that seen in the archaeal homologue . This family contains the archaeal beta subunit, eukaryotic prefoldin subunits 1, 2, 4 and 6.

Eukaryotic PFD has been shown to bind both actin and tubulin co-translationally. The chaperone then delivers the target protein to CCT, interacting with the chaperonin through the tips of the coiled coils. No authentic target proteins of any archaeal PFD have been identified, to date.
Signal recognition particle, SRP19 subunit (Signal_recog_particle_SRP19)
Type: Family

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the SRP19 subunit. The SRP19 protein is unstructured but forms a compact core domain and two extended RNA-binding loops upon binding the signal recognition particle (SRP) RNA .
Hydrogenase formation HypD protein (Hyd_form_HypD)
Type: Family

HypD is involved in the hyp operon which is needed for the activity of the three hydrogenase isoenzymes in Escherichia coli. HypD is one of the genes needed for formation of these enzymes . This protein has been found in Gram-negative and Gram-positive bacteria and Archaea. HypD contains many possible metal binding residues, which may bind to nickel. Transposon insertions into HypD resulted in Rhizobium leguminosarum mutants that lacked any hydrogenase activity in symbiosis with peas .
Transmembrane protein TauE-like (TM_pro_TauE-like)
Type: Family

This is a family of integral membrane proteins containing transmembrane helices. This family used to be known as DUF81.

The TauE proteins are involved in the transport of anions across the cytoplasmic membrane during taurine metabolism as an exporter of sulfoacetate .
Mut7-C RNAse domain (Mut7-C_RNAse_dom)
Type: Domain

This entry represents an RNAse domain of the PIN fold with an inserted zinc ribbon at the C terminus of probable exonuclease mut-7 .
Large ribosomal subunit protein eL14 domain (Ribosomal_eL14_dom)
Type: Domain

This entry includes the eukaryotic large ribosomal subunit protein eL14, which binds to the 60S 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 .
Inosine/xanthosine triphosphatase (Non_canon_purine_NTPase)
Type: Family

This is a family of prokaryotic phosphatases that hydrolyse non-canonical purine nucleotides such as XTP and ITP to their respective diphosphate derivatives. They probably exclude non-canonical purines from DNA precursor pool, thus preventing their incorporation into DNA and avoiding chromosomal lesions. ITP is the best substrate, followed by XTP, GDP or dITP .

Proteins in this entry include YjjX from E. coli. YjjX hydrolyzes non-canonical purine nucleotides such as XTP and ITP to their respective diphosphate derivatives. However, it is not active on dATP and dGTP, and exhibits no phosphatase activity toward pyrimidines (CTP, TTP, UTP, dCTP, and dTTP) .
Helicase HerA, central domain (HerA_central)
Type: Domain

This entry represents the central domain of archaeal protein HerA, which is a DNA helicase able to utilise either 3' or 5' single-stranded DNA extensions for loading and subsequent DNA duplex unwinding . It forms a complex with NurA nuclease, this complex has the 5'-3' DNA end resection activity and is essential for cell viability in the crenarchaeon Sulfolobus islandicus . Studies in Sulfolobus tokodaii revealed that HerA was able to unwind blunt-ended double-stranded DNA with low efficiency and it was also able to unwind Holliday junction, splayed-arm DNA, as well as 5'- or 3'-overhang with high efficiency . This domain includes the the central RecA-like catalytic core a flanking four-helix bundle .
Conserved hypothetical protein CHP00288 (CHP00288)
Type: Family

This entry describes archaeal proteins of unknown function. This family of orthologues is restricted to, but universal among, the completed archaeal genomes so far. Eubacterial proteins showing at least local homology include slr1870 from Synechocystis sp. (strain PCC 6803) and two proteins from Aquifex aeolicus, none of which is characterised.
Damage-control phosphatase ARMT1-like, metal-binding domain (ARMT1-like_metal-bd)
Type: Domain

This domain is found in Damage-control phosphatases ARMT1, YMR027W from S. cerevisiae (

) and At2g17340 from Arabidopsis thaliana, and it is also found at the C-terminal portion of eukaryotic pantothenate kinases . Despite the characterization of ARMT1 as a carboxyl methyltransferase, a second study suggests that these proteins are hydrolases whose function is to limit potentially harmful buildups of phosphometabolites . They are metal-dependent phosphatases involved in metabolic damage-control processes termed "damage pre-emption" or "housecleaning". Crystal structure of damage-control phosphatase At2g17340 revealed a novel protein fold and several conserved residues coordinating a metal ion (probably Mg2) with high degree of conservation suggesting that the metal-binding site is central for the function of this domain .
TRAM domain (TRAM_dom)
Type: Domain

The TRAM (after TRM2 and miaB) domain is a 60-70-residue-long module that is found in:

Two distinct classes of tRNA-modifying enzymes, namely uridine methylases of the TRM2 family and enzymes of the miaB family that are involved in 2- methylthioadenine formation

In several other proteins associated with the translation machinery

In a family of small archaeal proteins, including the RNA chaperone

from Methanococcus maripaludis and uncharacterised sequences that are predicted to have a role in the regulation of tRNA modification and/or translation

The TRAM domain can be found alone or in association with other domains, such as the catalytic biotin/lipoate synthetase-like domain, the RNA methylase domain, the ribosomal S2 domain and the eIF2-beta domain. The TRAM domain is predicted to bind tRNA and deliver the RNA-modifying enzymatic domain to their targets .

Secondary structure prediction indicates that the TRAM domain adopts a simple β-barrel fold. The conservation pattern of the TRAM domain consists primarily of small and hydrophobic residues that correspond to five β-strands in the predicted secondary structure .
Endonuclease NucS (Endonuclease_NucS)
Type: Family

Endonuclease NucS cleaves both 3' and 5' ssDNA extremities of branched DNA structures and it binds to ssDNA .