SII-SWORD/CoKE huggingface dataset:
DNA recombination/repair protein Rad52 (DNA_recomb/repair_Rad52)
Type: Family

Rad52 was identified in Saccharomyces cerevisiae (Baker's yeast) as a component of the homologous recombination repair pathway and to play an important role in both meiotic and mitotic recombination. The human protein is highly homologous in both structure and function. In the presence of absence of DNA, Rad52 forms ring-shaped oligomers which bind both single and double stranded DNA, stimulating annealing of complimentary DNA strands and promoting ligation of both cohesive and blunt-end fragments. Rad52 may act as a recombination mediator, optimising catalysis of strand exchange by the Rad51 protein.

A C-terminal self-association domain has been identified that mediates formation of higher order oligomers of Rad52 rings. Formation of these oligomers may be important for interaction with more than one DNA molecule .
RecBCD enzyme subunit RecB (RecB)
Type: Family

Exodeoxyribonuclease V, or RecBCD holoenzyme, (

) is a multifunctional nuclease with potent ATP-dependent exodeoxyribonuclease activity. Ejection of RecD, as occurs at chi recombinational hotspots, cripples exonuclease activity in favor of recombinagenic helicase activity. All proteins in this family for which functions are known are DNA-DNA helicases that are used as part of an exonuclease-helicase complex (made up of RecBCD homologues) that function to generate substrates for the initiation of recombination and recombinational repair. The complex catalyses exonucleolytic cleavage in either the 5' to 3' or 3' to 5' direction to yield 5-phosphooligonucleotides in the presence of ATP. This is the beta subunit .
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, bacterial-type (IspG_bac-typ)
Type: Family

This protein previously of unknown biochemical function is essential in Escherichia coli. It has now been characterised as 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, which converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4CPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the sixth step of nonmevalonate terpenoid biosynthesis. The family is largely restricted to bacteria, where it is widely but not universally distributed. No homology can be detected between this family and other proteins.
DNA helicase, ATP-dependent, RecQ type (DNA_helicase_ATP-dep_RecQ)
Type: Family

The ATP-dependent DNA helicase RecQ (

) is involved in genome maintenance . All homologues tested to date unwind paired DNA, translocating in a 3' to 5' direction and several have a preference for forked or 4-way DNA structures (e.g. Holliday junctions) or for G-quartet DNA. The yeast protein, Sgs1, is present in numerous foci that coincide with sites of
de novo
synthesis DNA, such as the replication fork, and protein levels peak during S-phase.

A model has been proposed for Sgs1p action in the S-phase checkpoint response, both as a 'sensor' for damage during replication and a 'resolvase' for structures that arise at paused forks, such as the four-way 'chickenfoot' structure. The action of Sgs1p may serve to maintain the proper amount and integrity of ss DNA that is necessary for the binding of RPA (replication protein A, the eukaryotic ss DNA-binding protein)-DNA pol complexes. Sgs1p would thus function by detecting (or resolving) aberrant DNA structures, and would thus contribute to the full activation of the DNA-dependent protein kinase, Mec1p and the effector kinase, Rad53p. Its ability to bind both the large subunit of RPA and the RecA-like protein Rad51p, place it in a unique position to resolve inappropriate fork structures that can occur when either the leading or lagging strand synthesis is stalled. Thus, RecQ helicases integrate checkpoint activation and checkpoint response.
DNA single-strand annealing protein RecT (ssDNA_annealing_RecT)
Type: Family

All proteins in this family for which functions are known bind single-stranded DNA and are involved in the the pairing of homologous DNA. RecT from Escherichia coli is a homotetramer which binds to single-stranded DNA and promotes the renaturation of complementary single-stranded DNA, and also plays a role in recombination. It is able to promote the annealing of complementary single
DNA strands and can catalyze the formation of joint molecules .
Replication factor A protein 1 (Rfa1)
Type: Family

Rfa1 (also known as RPA70) is a component of the replication protein A (RPA) complex, which binds to and removes secondary structure from ssDNA. The RPA complex is involved in DNA replication, repair, and recombination , and it also plays a role in telomere maintenance .
Nuclease SbcC, gammaproteobacteria type (SbcC_gammaproteobac_type)
Type: Family

This entry represents a small group of nuclease SbcCD subunit C (SbcC) proteins, mainly from gammaproteobacteria. SbcC are known are part of an exonuclease complex with sbcD homologues. SbcCD cleaves DNA hairpin structures. These structures can inhibit DNA replication and are intermediates in certain DNA recombination reactions. The complex acts as a 3'->5' double strand exonuclease that can open hairpins. It also has a 5' single-strand endonuclease activity .

The entry also includes a small number of proteins annotated as probable DNA double-strand break repair Rad50 ATPase, but which are experimentally uncharacterised.
Nuclease SbcCD subunit D (SbcD)
Type: Family

SbcCD cleaves DNA hairpin structures . This complex functions in the initiation of recombination and recombinational repair and is particularly important in regulating the stability of DNA sections that can form secondary structures . The complex acts as a 3'->5' double strand exonuclease that can open hairpins. It also has a 5' single-strand endonuclease activity .

This entry represent the SbcD subunit .
TFIIH C1-like domain (TFIIH_C1-like_dom)
Type: Domain

The carboxyl-terminal region of TFIIH is essential for transcription activity. This regions binds three zinc atoms through two independent domains. The first contains a C4 zinc finger motif, whereas the second is characterised by a CX(2)CX(2-4)FCADCD motif. The solution structure of the second C-terminal domain revealed homology with the regulatory domain of protein kinase C .
Cell division suppressor protein, SulA (Cell_div_suppressor_SulA)
Type: Family

All proteins in this family for which the functions are known are cell division inhibitors. In Escherichia coli, SulA is one of the SOS regulated genes. Accumulation of SulA causes rapid cessation of cell division and the appearance of long, non-septate filaments. In the presence of GTP, SulA binds a polymerisation-competent form of ftsZ in a 1:1 ratio, thus inhibiting ftsZ polymerisation and therefore preventing it from participating in the assembly of the Z ring. This mechanism prevents the premature segregation of damaged DNA to daughter cells during cell division . The expression of SulA is repressed by LexA. The N terminus of SulA may be involved in recognising the cell division apparatus.

SulA from Pseudomonas aeruginosa has been reported to have a fold similar to the nucleotide-binding core of RecA and form a dimer .
DNA-3-methyladenine glycosylase I (Tag)
Type: Family

One common form of damage to DNA occurs when alkyl groups become covalently linked to DNA, leading to the formation of mutagenic or toxic lesions. Alkylating agents are ubiquitous in the environment and can also exist endogenously; for example S-adenosylmethionine, a commonly used methyl donor in many cellualr pathways, can produce methylation damage. Given the prevalence of alkylating agents it is not surprising that all cellular organisms studied so far have developed repair systems to deal with DNA alkylation .

DNA-3-methyladenine glycosylase I (also known as TagI) is part of the broader helix-hairpin-helix DNA repair glycosylase supefamily. It specifically catalyses the release of 3-methylated adenine and, to a lesser extent, guanosine bases from DNA by hydrolysis of the deoxyribose N-glycosidic bond . A phylogenomic study suggests that TagI evolved in, and is specific to, the bacteria .
Transcription factor TFIIH subunit p52/Tfb2 (TFIIH_p52/Tfb2)
Type: Family

This entry represents the p52/Tfb2 subunit in the TFIIH complex, which is not only required for transcription but also plays a central role in DNA repair. The TFIIH multiprotein complex consists of a 7-subunit core (XPB, p62, p52, p44, p34, and TTDA) that is associated with a 3-subunit CDK-activating kinase module (MAT1, cyclin H and Cdk7) . The p52 subunit interacts with subunit XPB, which is an ATP-dependent 3'-5' DNA helicase, and stimulates its ATPase activity .
TFIIH subunit Tfb4/GTF2H3 (TFIIH_Tfb4/GTF2H3)
Type: Family

This entry represents Tfb4/GTF2H3, a component of the transcription factor TFIIH core (includes XPB, p62, p52, p44, p34). TFIIH complex is involved in the nucleotide excision repair (NER) and polymerase II transcription .
UV-endonuclease UvdE (UvdE)
Type: Family

Proteins in this family are a group of endonucleases for the repair of UV-irradiated DNA. Schizosaccharomyces pombe ultraviolet damage endonuclease (UVDE or Uve1p) is involved in the excision of cyclobutane pyrimidine dimers (CPD) and 6-4 pyrimidine pyrimidones (6-4PP) which forms the UV damage repair (UVDR) pathway. It also functions also in oxidative damage repair in vivo. It provides back-up AP endonuclease activity to apn2 together with apn1. This DNA repair pathway was originally thought to be specific for UV damage, however Uve1p also recognises UV-induced bipyrimidine photoadducts and other non-UV-induced DNA adducts .
UvrABC system subunit A (UvrA)
Type: Family

In Eubacteria and some Archaea, the first steps in nucleotide excision repair are carried out by the coordinated action of the UvrA, UvrB, and UvrC proteins. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. Upon binding of the UvrA(2)B(2) complex to a putative damaged site, the DNA wraps around one UvrB monomer. DNA wrap is dependent on ATP binding by UvrB and probably causes local melting of the DNA helix, facilitating insertion of UvrB β-hairpin between the DNA strands. Then UvrB probes one DNA strand for the presence of a lesion. If a lesion is found the UvrA subunits dissociate and the UvrB-DNA preincision complex is formed. This complex is subsequently bound by UvrC and the second UvrB is released. If no lesion is found, the DNA wraps around the other UvrB subunit that will check the other stand for damage .

This entry represents the UvrA subunit. UvrA is an ATPase and a DNA-binding protein .
DNA mismatch endonuclease VSR (DNA_mismatch_endonuc_vsr)
Type: Family

This entry represents VSR (very short patch repair) endonucleases occurring in a variety of bacteria and some archaeal species, including DNA mismatch endonuclease Vsr from Escherichia coli. VSR recognises a TG mismatched base pair, generated after spontaneous deamination of methylated cytosines, and cleaves the phosphate backbone on the 5' side of the thymine . GT mismatches can lead to C-to-T transition mutations if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In Escherichia coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine . The incision is mismatch-dependent and strand specific. The structure of VSR is similar to the core structure of restriction endonucleases, which have a 3-layer α/β/α topology .
DNA recombination/repair protein RecN (DNA_recomb/repair_RecN)
Type: Family

DNA repair protein RecN is thought to be DNA damage inducible and involved in recombinational processes. RecN is part of the AAA+ superfamily of ATPases. The N-terminal region of most of the bacterial RecN proteins sequenced to date contains an ATP/GTP binding domain within an SMC-like motif. SMC-like domains are involved in chromosomal scaffolding and segregation. It is possible that the function of RecN in homologous recombination is either structural or enzymatic or both. RecN may be involved in the proper positioning of the recombining segments of DNA, ensuring normal recombination. The observation that inactivation of this gene leads to a decreased transformation efficiency, as well as increased sensitivity to DNA-damaging agents, may be due to some defect in chromosomal partitioning or positioning during these recombination-dependent processes . The protein may function presynaptically to process double-stranded breaks to produce 3 single-stranded DNA intermediates during recombination.

The AAA+ superfamily of ATPases is found in all kingdoms of living organisms where they participate in diverse cellular processes including membrane fusion, proteolysis and DNA replication. Although the terms AAA+ and AAA are often used loosely and interchangeably, the classical AAA family members are distinguished by their possession of the SRH region in the AAA module. Many AAA+ proteins are involved in similar processes to those of AAA proteins (facilitation of protein folding and unfolding, assembly or disassembly of proteins complexes, protein transport and degradation), but others function in replication, recombination, repair and transcription. For a review see .
Holliday junction branch migration complex subunit RuvB (DNA_helicase_Holl-junc_RuvB)
Type: Family

This entry represents Holliday junction branch migration complex subunit RuvB, which as part of a complex with RuvA homologues serve as a 5'-3' Holliday junction helicase. RuvA specifically binds Holliday junctions as a sandwich of two tetramers and maintains the configuration of the junction. It forms a complex with two hexameric rings of RuvB, the subunit that contains helicase activity. The complex drives ATP-dependent branch migration of the Holliday junction recombination intermediate . The endonuclease RuvC resolves junctions.
Molybdenum-pterin binding domain (Mop_domain)
Type: Domain

Mop domains are present in a variety of bacterial and archeal proteins and specifically bind molybdate (or tungstate). The simplest mop-containing proteins are the so-called molbindins, consisting entirely of either one or two mop domains. The physiological role of these proteins is unclear, although they have been implicated in molybdate storage and homeostasis. Other mop-containing proteins are ModC, a component of the high affinity ABC transporter, and ModE, the molybdate-dependent transcriptional regulator .

The mop domain consists of 68 amino acid residues arranged in six β-strands linked by short loops. It contains a β-barrel comprised of five antiparallel β-strands in a Greek key arrangement that is capped by amphipathic two-turns α-helices. The mop domain structure corresponds to the canonical oligonucleotide/oligosaccharide binding (OB) fold .
Phosphoribosylglycinamide formyltransferase (GART)
Type: Family

Phosphoribosylglycinamide formyltransferase, also known as GAR transformylase or GART, is an essential enzyme that catalyzes the third step in de novo purine biosynthesis . This enzyme uses formyl tetrahydrofolate as a formyl group donor to produce 5'-phosphoribosyl-N-formylglycinamide. In prokaryotes, GART is a single domain protein but in most eukaryotes GART (purN) resides in the C-terminal portion of a large multifunctional protein which also contains GAR synthetase (purD) and aminoimidazole ribonucleotide (AIR) synthetase (purM) activities .
Methylmalonyl-CoA mutase, small subunit (MMCoA_mutase_b)
Type: Family

Methylmalonyl-CoA mutase (

) catalyses the isomerization of succinyl-CoA to methylmalonyl-CoA during the synthesis of propionate from tricarboxylic acid-cycle intermediates in propionic acid fermentation. The adenosylcobalamin-binding, catalytic chain of methylmalonyl-CoA mutase may form homodimers, as in the mitochondrion and in Escherichia coli, or heterodimers with a shorter, homologous chain that does not bind adenosylcobalamin. This family represents the non-catalytic beta chain (also known as the small subunit), as found in the enzyme from Propionibacterium freudenreichii, for which the 3-dimensional structure has been solved .
ATP-dependent DNA helicase RecG (ATP-dep_DNA_helicase_RecG)
Type: Family

The ATP-dependent DNA helicase RecG

plays a critical role in recombination and DNA repair. It helps to process Holliday junction intermediates to mature products by catalysing branch migration. This entry includes RecG from bacteria the homologue from Arabidopsis, which has a critical role in recombination and DNA repair. RecG has DNA unwinding activity characteristic of a DNA helicase with 3' to 5' polarity. RecG unwind branched duplex DNA (Y-DNA) and has a role in constitutive stable DNA replication (CsdR) and R-loop formation . It is genetically synergistic to RadA and RuvABC . RecG comprises three structural domains, the largest N-terminal Domain 1 which interacts with DNA junctions, and Domains 2 and 3 at the C-terminal which contain the characteristic motifs that identify RecG as an SF2 helicase .
Bacterial RecJ exonuclease (RecJ)
Type: Family

All proteins in this family are 5'-3' single-strand DNA exonucleases. These proteins are used in some aspects of mismatch repair, recombination, and recombinational repair. RecJ is a single-stranded DNA-specific endonuclease which is required for many types of recombination events, although the stringency of the requirement for RecJ appears to vary with the type of recombinational event monitored, and the other recombination gene products which are available .
DNA primase-related protein (DNA_primase-rel)
Type: Family

The DNA primase DnaG of Escherichia coli and its apparent orthologs in other bacterial species are approximately 600 residues in length. Within this set, a conspicuous outlier in percent identity, as seen in a UPGMA difference tree, is the branch containing the Mycoplasmas. This lineage is also unique in containing the small, DNA primase-related protein found in this family, which is homologous to the central third of DNA primase. Several small regions of sequence similarity specifically to Mycoplasma sequences rather than to all DnaG homologues suggests that the divergence of this protein from DnaG post-dated the separation of bacterial lineages. The function of this DNA primase-related protein is unknown.
Holliday junction resolvase RecU (Resolv_RecU)
Type: Family

This entry includes the Bacillus subtilis RecU protein and similar proteins predominantly found in Firmicutes. RecU has been shown to be required for DNA recombination and repair .
Ribonuclease J (RNase_J)
Type: Family

This family of proteins are about 50 to 77kDa. The central region is well conserved and contains three conserved histidines. Most of these proteins are related at the N-terminal region to the beta-lactamase family. The family has been characterised as ribonuclease J. RNase J cleaves the 5'-leader sequence of certain mRNAs and may play a role in the maturation and stability of specific mRNAs . It is also required for the maturation of the 16S rRNA acting preferentially on 16S rRNA precursors after association of the 30S and 50S ribosomal subunits .
Phosphate acetyltransferase (P_AcTrfase)
Type: Domain

Phosphate acetyltransferase (

) catalyses the conversion of acetyl-CoA and phosphate to CoA and acetyl phosphate in the last two steps in the conversion of actetae to acetyl-CoA.
DNA polymerase III, psi subunit (DNA_pol_III_psi)
Type: Family

DNA-directed DNA polymerase (

) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of alpha, epsilon and theta chains, that associate with a tau subunit which allows the core dimerization to form the PolIII' complex. PolIII' associates with the gamma complex (gamma, delta, delta', psi and chi chains) and with the beta chain. This family is the psi subunit, the small subunit of the DNA polymerase III holoenzyme in Escherichia coli and related species, whose exact function is not known. It appears to have a narrow taxonomic distribution, being restricted to the gammaproteobacteria.
Leucyl/phenylalanyl-tRNA-protein transferase (Leu/Phe-tRNA_Trfase)
Type: Family

Leucyl/phenylalanyl-tRNA--protein transferase

transfers a Leu or Phe to the amino end of certain proteins to enable degradation. The N-terminal residue controls the biological half-life of many proteins via the N-end rule pathway.
Bis(5'-nucleosyl)-tetraphosphatase, symmetrical (ApaH)
Type: Family

This protein family represents Bis(5'-nucleosyl)-tetraphosphatase, symmetrical (ApaH, also known as Ap4A hydrolase) from Escherichia coli and similar proteins predominantly found in Proteobacteria. This enzyme hydrolyses diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), a regulatory metabolite of stress conditions, to yield ADP .
Aspartate--ammonia ligase (AsnA)
Type: Family

Aspartate--ammonia ligase (asparagine synthetase)

catalyses the conversion of L-aspartate to L-asparagine in the presence of ATP and ammonia. This family represents one of the two non-homologous forms of aspartate--ammonia ligase found in Escherichia coli. This type is also found in Haemophilus influenzae, Treponema pallidum and Lactobacillus delbrueckii, but appears to have a very limited distribution. The fact that the protein from the H. influenzae is more than 70% identical to that from the spirochete T. pallidum, but less than 65% identical to that from the closely related E. coli, strongly suggests lateral transfer.

AsnA is a homodimeric enzyme which is structurally similiar to the catalytic core domain of class II aminoacyl-tRNA synthetases. Ammonia-dependent AsnA is not homologous to the glutamine-dependent asparagine synthetase AsnB .
Type III pantothenate kinase (Type_III_PanK)
Type: Family

This entry represents the type III pantothenate kinase family, such as that found in Helicobacter pylori. PanK III enzymes have a much wider phylogenic distribution than PanK I, and differs significantly in biochemical activity. PanK III enzymes are are not feedback inhibited by CoA concentration (which is also the case for PanK II enzymes), and PanK III enzymes have an unusually high Km for ATP .

Pantothenate kinase (PanK or CoaA) catalyses the first step of the universal five step coenzyme A (CoA) biosynthesis pathway. CoA is a ubiquitous and essential cofactor in all living organsims. Pantothenate kinase catalyses the first and rate limiting step in the CoA biosynthetic pathway, which involves transferring a phosphoryl group from ATP to pantothenate, also known as vitamin B5. Three distinct types of pantothenate kinase enzymes have been identified: type I PanK enzymes are typified by the E. coli CoaA protein, type II enzymes are primarily found in eukaryotic organisms whilst type III enzymes have a wider phylogenic distribution and are not feedback inhibited by CoA .
5,10-methylenetetrahydrofolate reductase (MTHF_reductase_bac)
Type: Family

This entry represents a family that includes bacterial 5,10-methylenetetrahydrofolate reductase (FADH).

The enzyme activities methylenetetrahydrofolate reductase (

) and 5,10-methylenetetrahydrofolate reductase (FADH) (

) differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both generate 5-methyltetrahydrofolate from 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in prokaryotes, and currently designated 5,10-methylenetetrahydrofolate reductase (FADH) (

). This protein is an FAD-containing flavoprotein .