SII-SWORD/CoKE huggingface dataset:
ATP-dependent Clp protease ATP-binding subunit ClpA (ClpA)
Type: Family

Proteins in this entry are related to ClpA (

) from Escherichia coli. ClpA is an ATP-dependent chaperone and part of the ClpAP protease that participates in regulatory protein degradation and the dissolution and degradation of protein aggregates . ClpA functions as the regulatory component of the ATP dependent protease complex ClpAP . ClpA recognises sequences in specific proteins, which it then unfolds in an ATP-dependent manner and transports into the degradation chamber of the associated ClpP protease . A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein . It protects ClpA from autodegradation and appears to redirect its activity away from soluble proteins and toward aggregated proteins.
Gas vesicle protein GvpN (Gas-vesicle_GvpN)
Type: Family

The GvpN protein is associated with the production of gas vesicles produced in some prokaryotes to give cells buoyancy . It belongs to a larger family of ATPases .
Conserved hypothetical protein CHP02642 (CHP02642)
Type: Family

This uncharacterised protein is found in prophage regions of Shewanella oneidensis MR-1, Vibrio vulnificus (strain YJ016), Yersinia pseudotuberculosis IP 32953, and Aeromonas hydrophila subsp. hydrophila (strain ATCC 7966/NCIB 9240). It appears to have regions of sequence similarity to the phage lambda antitermination protein Q.
Thymidine phosphorylase (Thymidine_Pase)
Type: Family

Thymidine phosphorylase (alternate name: pyrimidine phosphorylase)

is involved, in Escherichia coli and other Proteobacteria, in (deoxy)nucleotide degradation. It is often encoded in an operon together with a deoxyribose-phosphate aldolase, a phosphopentomutase and a purine nucleoside phosphorylase. In many other lineages, the corresponding enzyme is designated pyrimidine-nucleoside phosphorylase (

); the naming convention here follows standard literature practice.
Thymidine phosphorylase/AMP phosphorylase (Thymidine/AMP_Pase)
Type: Family

Proteins in this entry are closely related to characterised examples of thymidine phosphorylase (

) and pyrimidine nucleoside phosphorylase (

). Many examples are found in the archaea, but other examples are found in bacteria such as Legionella pneumophila (strain Paris) and Rhodopseudomonas palustris CGA009.
Retron Ec78 putative HNH endonuclease-like (HNH78-like)
Type: Family

This entry represents a bacterial family of proteins that includes several putative HNH endonucleases that form part of antiviral defense systems such as Ec78, Ec83 and Vc95. These proteins confer protection against specific phages .

This entry also includes Septu protein PtuB, a component of antiviral defense system Septu type II .
Conserved hypothetical protein CHP02647 (CHP02647)
Type: Family

Proteins in this entry are found, so far, only in the Gammaproteobacteria. Their function is currently unknown. The location on the chromosome is usually not far from housekeeping genes. Some proteins have been annotated in public databases as DNA-binding protein inhibitor-related, putative transcriptional regulators, or hypothetical DNA binding proteins.
Ribonuclease BN (Rnase_BN)
Type: Family

This entry represents the ribonuclease Z (RNase Z) homologue, RNase BN, from bacteria. RNase BN was considered to be an exonuclease based on its ability to remove the 3'-terminal residue of tRNAs ending in CA, CU, CCU or even CCA . In E. coli, even though different set of enzymes are used for tRNA 3'-ends processing and RNase Z is thought to be less important than the other ribonucleases. However, E. coli cells lacking the four main enzymes of the exonucleolytic pathway (RNases T, PH, D and II) are viable, whereas further mutation of RNase BN/Z in this genetic context causes an unviable phenotype .
Ribonuclease Z, Thermotoga-type (RNase_Z_T_toga)
Type: Family

All tRNA molecules are synthesised as long precursors with extra sequence at both the 5' and 3' ends, which undergo several processing steps to form the mature tRNA molecule. In many bacteria, the tRNA precursors do not contain the CCA sequence which forms the 3' end of the mature tRNA and is essential for aminoacylation. In these organisms ribonucleotide Z cleaves the precursor to form a 3' end to which CCA is added. Proteins in this entry, by contrast, are ribonuclease Z enzymes with unusual activity, found in the genus Thermotoga, which include the CCA sequence in the tRNA precursor and ribonuclease Z cleaves the molecule immediately after this sequence producing a mature 3' end. The sequence of these proteins differs considerably from the majority of ribonuclease Z sequences .
Ribonuclease Z/BN (RNase_Z/BN)
Type: Family

This entry includes ribonuclease Z (RNase Z) and its orthologues, such as RNase BN (also known as elaC) from E.coli. They are ribonucleases that have functions in tRNA-3' processing. RNase Z orthologues are present in all eukaryotes and archaea sequenced so far, and are widely distributed in bacteria .

All tRNAs are synthesized as precursor molecules and their maturation to functional tRNAs requires several processing steps. First, the removal of the 5'-leader is catalysed by the endonucleolytic ribozyme RNase P. Second, the removal of the 3'-trailer sequences, which is either a single-step endonucleolytic process or a two-step process involving downstream cleavage by an endonuclease followed by exonucleolytic trimming to generate the mature 3'-end .

The first evidence for the maturation of tRNA 3'-ends by a single endonucleolytic cleavage reaction came from eukaryotes. In these cases, the cleavage of the 3'-end is carried out by RNase Z. In most cases, RNase Z removes the 3'-trailer sequence by cleaving directly after the discriminator nucleotide. Interestingly, the CCA motif present in all mature tRNAs is a general anti-determinant for RNase Z activity. The activity of some RNase Z homologues found in bacterial and archaea have also been shown to be inhibited by the presence of a CCA motif .
Conserved hypothetical protein CHP02652 (CHP02652)
Type: Family

These conserved hypothetical proteins have so far been found only in the Cyanobacteria. They are about 170 amino acids long and contain a CxxCx(14)CxxH motif near the N terminus.
Lon-like protease BrxL (BrxL)
Type: Family

This family represents the Lon-like protease BrxL, including BrxL from Bacillus cereus, which is part of a type 1 BREX system. BREX systems (bacteriophage exclusion) provide immunity against bacteriophage, a system that allows phage adsorption but prevents phage DNA replication, without degradation of the phage DNA . Methylation of bacterial DNA by PglX probably guides self/non-self discrimination. When the brxA-brxB-brxC-pglX and pglZ-brxL operons are transformed into a susceptible B.subtilis strain (BEST7003) they confer resistance to bacteriophages SPbeta, SP16, Zeta, phi3T and SP02 and partial protection to phages SP01 and SP82G (these include lytic and temperate phage).
Circadian clock protein KaiB (Circ_KaiB)
Type: Family

The cyanobacterial circadian clock protein KaiB is encoded in the kaiABC operon that controls circadian rhythms. It is a component of the KaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria . KaiB forms homodimers, homotetramers, and multimeric complexes with KaiA and/or KaiC . KaiB-KaiC binding is accompanied by a dramatic reduction in KaiC phosphorylation and followed by dissociation of the clock protein complex .
Amicyanin, Paracoccus/Methylobacterium (Amicyanin_Para/Methyl)
Type: Family

Amicyanin is a type I blue copper protein that accepts electrons from the tryptophan tryptophylquinone (TTQ) cofactor of the methylamine dehydrogenase light chain and then transfers them to the haem group of cytochrome c-551i. Amicyanin, methylamine dehydrogenase, and cytochrome c-551i are located in the periplasm and form a complex. This system has been studied primarily in Paracoccus denitrificans and Methylobacterium extorquens. Related type I blue copper proteins include plastocyanin, pseudoazurin, halocyanin, etc.
Methylamine dehydrogenase heavy chain (MeN_DH_Hvc)
Type: Family

Methylamine dehydrogenase is a periplasmic enzyme found in Gram-negative methylotrophs and consists of a heavy chain (large subunit) and a light chain (small subunit), forming a heterotetramer . It is induced when grown on methylamine as a growth substrate and catalyses the oxidative deamination of primary amines to their corresponding aldehydes. This entry represents the methylamine dehydrogenase heavy chain.
Homocitrate synthase NifV-like (NifV/FrbC)
Type: Family

Homocitrate synthase NifV catalyzes the condensation of acetyl coenzyme A and 2-oxoglutarate to form homocitrate and CoA. Homocitrate is a component of the FeMo-cofactor present in the catalytic centre of dinitrogenase . This family includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus. Most NifV-type homocitrate synthases are encoded within operons for nitrogen fixation .

FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and 2-oxoglutarate, a reaction similar to one catalyzed by homocitrate synthase. FrbC is also the 2-phosphonomethylmalate synthase (

) that catalyses the condensation of acetyl-CoA and 3-phosphonopyruvate, one of the steps required in the biosynthesis of FR900098, a potent antimalarial antibiotic . This protein is also required for assembly of the nitrogenase MoFe complex, but its exact role is unknown .
Methylamine dehydrogenase accessory protein MauD (MeN_DH_accessory)
Type: Family

MauD appears critical to proper formation of the small subunit of methylamine dehydrogenase, which has both an unusual tryptophan tryptophylquinone cofactor and multiple disulphide bonds. MauD shares sequence similarity, including a CPxC motif, with a number of thiol:disulphide interchange proteins. In MauD mutants, the small subunit apparently does not form properly and is rapidly degraded .
ADP-ribosyl-dinitrogen reductase hydrolase (ADP-ribosyl_diN_reduct_hydro)
Type: Family

This entry represents ADP-ribosyl-dinitrogen reductase hydrolase (

), also known as dinitrogenase reductase activating glycohydrolase (DraG). It is involved in the regulation of nitrogen fixation activity by the reversible ADP-ribosylation of the dinitrogenase reductase component of the nitrogenase enzyme complex . The ADP-ribosyltransferase protein DraT acts to inactivate dinitrogen reductase by adding an ADP-ribose group to this enzyme. DraG, in contrast, activates this enzyme by removing the attached ADP-ribose group.
Nitrogen fixation protein NifX (NifX)
Type: Family

NifX is involved in the biosynthesis of the iron-molybdenum cofactor (FeMo-Co) found in the dinitrogenase enzyme of the nitrogenase complex in nitrogen-fixing bacteria. This complex catalyses the reduction of atmospheric dinitrogen to ammonia. The role of NifX in cofactor biosynthesis is not fully understood, though it appears to be associated with mature FeMo-Co and may be involved in the addition of heterometal and/or homocitrate .
Nitrate reductase maturation protein NarM (NarM)
Type: Family

Most members of this protein family are found in the Cyanobacteria, and these mostly near nitrate reductase genes and molybdopterin biosynthesis genes. Molybdopterin guanine dinucleotide is a cofactor for nitrate reductase. Partially characterised members have been designated NarM and shown to be required for nitrate reductase activity .
Molybdenum cofactor guanylyltransferase (Molybde_CF_guanTrfase)
Type: Family

In many molybdopterin-containing enzymes, including nitrate reductase and dimethylsulfoxide reductase, the cofactor is molybdopterin-guanine dinucleotide (molybdopterin modified by attachment of a GMP group to the terminal phosphate). This entry represents the molybdenum cofactor guanylyltransferase MobA. In E. coli, MobA transfers a GMP moiety from GTP to the Mo-molybdopterin (Mo-MPT) cofactor (Moco or molybdenum cofactor) to form the Mo-molybdopterin guanine dinucleotide (Mo-MGD) cofactor. MobA is also involved in the biosynthesis of the bis-MGD form of the Moco cofactor (Mo-bisMGD) in which the metal is symmetrically ligated by the dithiolene groups of two MGD molecules. It is necessary and sufficient for the in vitro activation of the DMSOR molybdoenzyme that uses the Mo-bisMGD form of molybdenum cofactor, which implies formation and efficient insertion of the cofactor into the enzyme without the need of a chaperone. It is specific for GTP since other nucleotides such as ATP and GMP can not be utilised .
Molybdenum cofactor biosynthesis protein A (MoaA)
Type: Family

This entry represents the MoaA protein (molybdenum cofactor biosynthesis protein A), also known as cyclic pyranopterin monophosphate synthase or GTP 3',8-cyclase.

MoaA is a member of the wider S-adenosylmethionine(SAM)-dependent enzyme family which catalyze the formation of protein and/or substrate radicals by reductive cleavage of SAM via a [4Fe-4S] cluster. Monomeric and homodimeric forms of MoaA have been observed
in vivo
, and it is not clear what the physiologically relevant form of the enzyme is . The core of each monomer consists of an incomplete TIM barrel, formed by the N-terminal region of the protein, containing a [4Fe-4S] cluster. The C-terminal region of the protein, which also contains a [4Fe-4S] cluster consists of a β-sheet covering the lateral opening of the barrel, an extended loop and three α-helices. The N-terminal [4Fe-4S] cluster is coordinated with 3 cysteines and an exchangeable SAM molecule, while the C-terminal [4Fe-4S], also coordinated with 3 cysteines, is the binding and activation site for GTP .

The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism .
Molybdenum cofactor biosynthesis protein B, proteobacteria (MoaB_proteobac)
Type: Family

MoaB is thought to be involved in molybdopterin biosynthesis, though its exact role is not known. Structural studies of this polypeptide suggest that it may play a role in substrate-shuttling during biosynthesis . MoaB was capable of binding GTP, and it was suggested that the putative active site could also bind precursor Z and/or molybdenum. Potential protein interaction domains were also found, implying that MoaB may play a transport and/or storage role in molybdopterin biosynthesis.
Molybdenum cofactor biosynthesis protein A, archaea (MoaA_arc)
Type: Family

This entry consists of archaeal proteins which are predicted to be functionally equivalent to MoaA (molybdenum cofactor biosynthesis protein A, cyclic pyranopterin monophosphate synthase or GTP 3',8-cyclase) from bacteria (see

).
Sporulation stage II protein D, amidase enhancer LytB (SpoIID/LytB)
Type: Family

This entry describes a region which is found, typically in two or three proteins per genome, in Cyanobacteria and Firmicutes, and sporadically in other genomes. One example is SpoIID from Bacillus subtilis. Another, also from B. subtilis, is LytB which contains this region at the C terminus. LytB is encoded immediately upstream of an amidase, the autolysin LytC, and both these proteins show considerable homology in their N-terminal regions. Genes encoding proteins in this entry do not occur in conserved neighbourhoods, and many, such as SpoIID are monocistronic. One modeling study has suggested that SpoIID may bind DNA, but the function of these proteins is so far unknown.
CRISPR-associated protein Csx8 (CRISPR-assoc_prot_Csx8)
Type: Family

This entry represents the Cxs8 family of Cas proteins, whose function is unknown. These proteins are encoded in the midst of a cas gene operon, immediately upstream of CRISPR-associated autoregulator, DevR family (

) .

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.
CRISPR-associated protein Csx9/Cas8a2 (CRISPR-assoc_prot_Csx9/Cas8a2)
Type: Family

This entry represents the Cxs9/Cas8a2 family of Cas proteins found in archaea. These proteins are encoded in the midst of a cas gene operon is found immediately upstream of cas3 in loci that resemble the Apern type but lack Csa1 and Csa4 genes .

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.
CRISPR-associated protein Csm6 (CRISPR-assoc_prot_Csm6)
Type: Family

This entry represents the Csm6 family of Cas (CRISPR-associated) proteins found in bacteria, such as Streptococcus thermophilus CNRZ1066, Staphylococcus epidermidis RP62A, and Mycobacterium tuberculosis (strains CDC1551 and H37Rv), as part of Mtube-type CRISPR/Cas systems, now called type III-A. Csm6 is a CARF (CRISPR-associated Rossmann fold) superfamily protein, that acts as a standalone RNase that degrades invader RNA transcripts after allosteric activation by cyclic oligoadenylates (cOA), which are produced by Cas10 subunit in the interference complex upon target RNA binding. These cOA bind to Csm6's CRISPR-associated Rossmann fold (CARF) domain . CRISPR is a widespread form of direct repeat found in archaea and bacteria, with distinctive subtypes each of which has a characteristic sporadic distribution .
CRISPR-associated RAMP Csx10 (CRISPR-assoc_RAMP_Csx10)
Type: Family

This entry represents the Csx10 family of Cas proteins, which are largely restricted to cyanobacteria .

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.
Tape measure protein N-terminal (Tape_meas_N)
Type: Domain

This entry is represented by a N-terminal domain of tape measure proteins that characterises the Caudoviruses. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

Proteins containing this domain are found either in bacteriophages or in bacteria, where they are encoded in bacteriophage and prophage regions. Most members are 800 to 1800 amino acids long, making them among the longest predicted proteins of their respective phage genomes, where they are encoded in tail protein regions. This roughly 80-residue domain described here usually begins between residue 100 and 250. Many members are known or predicted phage tail tape measure proteins, a minor tail component that regulates tail length.
CRISPR system subtype II-B RNA-guided endonuclease Cas9/Csx12 (CRISPR-assoc_Cas9/Csx12)
Type: Family

This entry represents a family of large Cas proteins that have so far only been found in CRISPR/cas loci in Francisella tularensis,
Wolinella succinogenes DSM 1740, and Legionella pneumophila (strain Paris) . One region of this large protein shows sequence similarity to HNH endonuclease

.

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.
Conserved hypothetical protein CHP02677 (CHP02677)
Type: Family

Proteins in this family are encoded within a conserved gene four-gene neighbourhood found sporadically in a phylogenetically broad range of bacteria including: Nocardia farcinica, Symbiobacterium thermophilum, Streptomyces avermitilis (Actinobacteria), Geobacillus kaustophilus (Firmicutes), Azoarcus sp. (strain EbN1) (Aromatoleum aromaticum (strain EbN1)) and Ralstonia solanacearum (Betaproteobacteria).
Conserved hypothetical protein CHP02678 (CHP02678)
Type: Family

Proteins in this family are encoded within a conserved gene four-gene neighbourhood found sporadically in a phylogenetically broad range of bacteria including: Nocardia farcinica, Symbiobacterium thermophilum, Streptomyces avermitilis (Actinobacteria), Geobacillus kaustophilus (Firmicutes), Azoarcus sp. (strain EbN1) (Aromatoleum aromaticum (strain EbN1)) and Ralstonia solanacearum (Betaproteobacteria).
Conserved hypothetical protein CHP02679 (CHP02679)
Type: Family

Proteins in this family are encoded within a conserved gene four-gene neighbourhood found sporadically in a phylogenetically broad range of bacteria including: Nocardia farcinica, Symbiobacterium thermophilum, Streptomyces avermitilis (Actinobacteria), Geobacillus kaustophilus (Firmicutes), Azoarcus sp. (strain EbN1) (Aromatoleum aromaticum (strain EbN1)) and Ralstonia solanacearum (Betaproteobacteria).
Conserved hypothetical protein CHP02680 (CHP02680)
Type: Family

Proteins in this entry are encoded within a conserved gene four-gene neighbourhood found sporadically in a phylogenetically broad range of bacteria including: Nocardia farcinica, Symbiobacterium thermophilum, and Streptomyces avermitilis (Actinobacteria), Geobacillus kaustophilus (Firmicutes), Azoarcus sp. (strain EbN1) (Aromatoleum aromaticum (strain EbN1)) and Ralstonia solanacearum (Betaproteobacteria). These proteins average over 1400 amino acids in length.
DNA topoisomerase, type IA, central (Topo_IA_cen)
Type: Domain

Type IA topoisomerases are comprised of four domains that together form a toroidal structure with a central hole large enough to accommodate single- and double-stranded DNA: an N-terminal α/β Toprim domain, domain 2 and the C-terminal domain 4 are winged-helix domains, and domain 3 is a β-barrel. Domains 1 (Toprim) and 3 form the active site of the enzyme, while the winged helix domains 2 and 4 form a single-strand DNA-binding groove . This entry represents the central portion of the enzyme, which covers domains 2 and 3 in topoisomerase type IA enzymes.

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .