SII-SWORD/CoKE huggingface dataset:
Spo16 protein, N-terminal domain (Spo16_N)
Type: Domain

This entry represents a nuclease-like domain of Spo16, similar to that in ERCC1 .

This entry represents proteins related to budding yeast Spo16, which belongs to a conserved meiosis-specific group of proteins known as ZMM (Zip, Msh, Mer), which are critical for the control and crossover formation during gametogenesis. Spo16 forms a complex with Zip2 and Zip4. Zip2 and Spo16, form a meiosis-specific XPF-ERCC1-like complex. The recombinant Zip2 XPF domain together with Spo16 preferentially binds branched DNA structures, such as D loops and HJs. It is suggested that Zip2-Spo16 forms a 'nuclease-inactive' heterodimer that recognises DNA junctions during meiotic homologous recombination and then recruits other factors for DNA repair. Moreover, together with Zip2 and Zip4, Spo16 also plays a key role in synaptonemal complex assembly . The Spo16 protein contains a C-terminal HHH motif.
DisA glycoprotein (DisA_glycoprotein)
Type: Family

This entry corresponds to a putative viral glycoprotein also called ORF2, found in Negevirus .
AF4 interaction motif (AF4_int)
Type: Conserved_site

This short motif is found in the AF4 protein and interacts with AF9 .

The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression .

In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) .
AF4/FMR2, C-terminal homology domain (AF4/FMR2_CHD)
Type: Domain

The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression .

In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) .

This entry also includes Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila .

This entry represents the C-terminal domain homology domain (CHD) that is conserved among AF4/FMR2 family proteins, including AFF1, AFF2, AFF3, and AFF4. This domain consists of eight helices and is distantly related to tetratricopeptide repeat motifs. The CHD domain mediates the formation of an AFF4 homodimer or an AFF1-AFF4 heterodimer. . This domain is essential for AFF4 interaction with Transcription Start Site (TSS)-associated histone H3K27 whose acetylation signals SEC to regulate transcriptional elongation of the ESR1 gene . Depletion of AFF4 reduces expression of ESR1, and, consequently inhibits breast cancer cell growth .
PPE-PPW subfamily, C-terminal (PPE-PPW_C)
Type: Domain

This entry represents the C-terminal region of a subfamily of PPE protein family known as the PPW subfamily . The PPW refers to three conserved residues found in the sequence alignment. The region also contains a second conserved motif GFGT.
Peripherally associated ATOM36 (pATOM36)
Type: Family

This entry represents the trypanosome peripherally associated ATOM36 protein (pATOM36) which is an essential component of the outer mitochondrial membrane protein import system that interacts with ATOM (archaic translocase of the outer mitochondrial membrane), being involved in the assembly and/or membrane insertion of proteins included in the ATOM complex. This protein also promotes protein translocation into the mitochondrial matrix .
Chroparavirus methyltransferase domain (Chropara_Vmeth_dom)
Type: Domain

This entry represents a domain found in the N-terminal region of chroparavirus proteins that is homologous to

. Included in chroparavirus are chronic bee paralysis virus, anopheline-associated C virus and Lake Sinai virus. These proteins are likely methytransferases involved in mRNA capping .
Nodavirus methyltransferase domain (Noda_Vmethyltr_dom)
Type: Domain

This entry represents a domain found in the N-terminal region of nodavirus proteins that is homologous to

. These proteins are likely methytransferases involved in mRNA capping .
KNL1 MELT repeat (KNL1_MELT_rpt)
Type: Repeat

The outer kinetochore protein scaffold KNL1 is crucial for a correct chromosome segregation during mitosis and meiosis. The main characteristic of KNL1 is the presence of repeats containing MELT (Met-Glu-Leu-Thr) motifs which are phosphorylated and critical for the BUB1-BUB3 dimer recruitment. BUB1-BUB3 dimer regulates chromosome biorientation and the spindle assembly checkpoint . This entry mainly represents vertebrate proteins although MELT motifs are found much more widely.
Crescentin, coiled-coil domain (CreS_CC)
Type: Domain

This entry represents the coiled-coil region of crescentin found in alphaproteobacteria. The coiled coil domain prives structural stability to crescentin filaments, allowing them to maintain their shape and function .

CreS is the bacterial equivalent to Intermediate Filament (IF) proteins from eukaryotes. Its cytoskeletal function is required for the vibrioid and helical shapes of Caulobacter crescentus in which it was seen that without CreS, the cells adopt a straight-rod morphology. This protein, similarly to IF proteins, can assemble itself into filaments in vitro with no need of energy or additional cofactors. In vivo, it forms a helical structure that colocalises with the inner cell curvatures beneath the cytoplasmic membrane . CreS possesses the typical tripartite IF-like domain architecture found in IF proteins, which contains a coiled-coil rod domain with short head (N-terminal) and tail (C-terminal) domains .
Domain of unknown function DUF5880 (DUF5880)
Type: Domain

This entry describes proteins of unknown function found mostly in Bacillariophyta.
Protein of unknown function DUF5879 (DUF5879)
Type: Family

This is a family of uncharacterised proteins of unknown function found in pandoraviruses.
Domain of unknown function DUF5878 (DUF5878)
Type: Domain

The function of this domain is unknown, it appears to be restricted to pandoraviruses.
Protein of unknown function DUF5877 (DUF5877)
Type: Family

This is a family of uncharacterised proteins of unknown functions found in Iridoviridae.
Protein of unknown function DUF5876 (DUF5876)
Type: Family

This is a family of uncharacterised proteins of unknown functions found in Iridoviridae.
Protein of unknown function DUF5875 (DUF5875)
Type: Family

This is a family of uncharacterised proteins of unknown functions found in Iridoviridae.
Exolysin-like, DUF5874 (Exolysin_DUF5874)
Type: Domain

This domain is found in Exolysin and related sequences predominantly found in Phycodnaviridae. Exolysin is involved in the degradation of the host cell wall at the site of attachment during viral entry . The function of this domain is unknown.
Domain of unknown function DUF5873 (DUF5873)
Type: Domain

This domain is found in proteins of unknown function predominantly found in Phycodnaviridae.
NAD-protein ADP-ribosyltransferase ModB-like (ModB-like)
Type: Family

This entry represents a family of NAD-protein ADP-ribosyltransferases mostly from Myoviridae, incluidng ModB from the bacteriophage T4 .

Bacteriophage T4 encodes three ADP-ribosyltransferases: Alt, ModA, and ModB. The ADP-ribosylating activity of each is directed to a specific set of host proteins. ModB ADP-ribosylates a number of host proteins including ribosomal protein S1 .

Protein ADP-ribosylation is an important posttranslational modification catalyzed by a group of enzymes known as ADP-ribosyltransferases (ADP-RTs) . ADP-RTs transfer single or multiple ADP-ribose moieties from NAD to a specific amino acid residue within a target protein, forming mono ADP-ribosylation or poly ADP-ribosylation (PARylation) . ADP-ribosylation changes the electrostatic potential of a target protein by introducing two phosphate groups and may affect protein-DNA as well as protein-protein interactions . Protein ADP-ribosylation plays versatile roles in multiple biological processes.
NAD-protein ADP-ribosyltransferase ModA-like (MODA-like)
Type: Family

This entry represents a family of NAD-protein ADP-ribosyltransferases found in Myoviridae, including ModA from the bacteriophage T4 .

Bacteriophage T4 codes for three ADP-ribosyltransferases: Alt, ModA, and ModB. The ADP-ribosylating activity of each is directed to a specific set of host proteins. ModA is known to modify subunits of RNA-polymerase .

Protein ADP-ribosylation is an important posttranslational modification catalyzed by a group of enzymes known as ADP-ribosyltransferases (ADP-RTs) . ADP-RTs transfer single or multiple ADP-ribose moieties from NAD to a specific amino acid residue within a target protein, forming mono ADP-ribosylation or poly ADP-ribosylation (PARylation) . ADP-ribosylation changes the electrostatic potential of a target protein by introducing two phosphate groups and may affect protein-DNA as well as protein-protein interactions . Protein ADP-ribosylation plays versatile roles in multiple biological processes.
Flap endonuclease D15-like (FEN_D15-like)
Type: Family

Flap endonucleases (FENs) catalyse the exonucleolytic hydrolysis of blunt-ended duplex DNA substrates and the endonucleolytic cleavage of 5'-bifurcated nucleic acids at the junction formed between single and double-stranded DNA
. This entry represents a group of flap endonucleases from Caudovirales, including D15 from Escherichia phage T5. D15 catalyzes both the 5'-exonucleolytic and structure-specific endonucleolytic hydrolysis of DNA branched nucleic acid molecules and probably plays a role in viral genome replication . The structure of D15 from the T5 phage reveals a central 6-strand β-sheet with a cluster of α-helices on either side .
Carbamoyl-phosphate synthase (CPSase_Archaea)
Type: Family

This entry includes carbamoyl-phosphate synthase (CPSase) from archaea, including MS-s from M. smithii. MS-s is homologous to the CPS.B subdomain of E. coli but is significantly smaller, 367 vs 513 residues, respectively. It synthesises carbamoyl phosphate from ATP, bicarbonate, and ammonia, and catalyses the same ATP-dependent partial reactions observed for full-length CPSases .
Glucosamine kinase (GlcN_kinase)
Type: Family

This entry represents glucosamine kinase mostly from Actinobacteria, including GlcN kinase from S. jiangxiensis (known as SjGlcNK). SjGlcNK contains a fold similar to mycobacterial maltokinases. However, SjGlcNK was unable to phosphorylate maltose or aminoglycosides in vitro. Instead, it catalyses the ATP-dependent phosphorylation of D-glucosamine (GlcN) to D-glucosamine 6-phosphate .
tRNA 5-hydroxyuridine methyltransferase (TrmR_methyltr)
Type: Family

This entry includes tRNA 5-hydroxyuridine methyltransferase from bacteria, including TrmR from Bacillus subtilis. TrmR catalyses the methylation of 5-hydroxyuridine (ho5U) to form 5-methoxyuridine (mo5U) at position 34 in tRNAs .
Glucosyltransferase 3 (Gtf3)
Type: Family

Glucosyltransferase 3 (also known as Glucosyltransferase C, GtfC) catalyses the second step of glycosylation of Serine-rich repeat glycoproteins (SRRPs) in Gram-positive bacteria and transfers glucosyl residues to GlcNAc-modified SRRPs. SRRPs have been first identified in pathogenic bacteria but they are also in gut commensal bacteria. These proteins are O-glycosylated on serine or threonine residues to be exported via an specialised accessory secretion (SecA2/Y2) system. This secretion system is encoded in a gene cluster that includes the motor protein SecA2, the channel SecY2 and three to five accessory Sec proteins, but it also contains genes encoding a variable number of glycosyltransferases (GTs), among them Gft3 .

Structural analysis revealed that Gft3 forms a tetramer and has structural homology with other glycosyltransferases. The conserved residues Phe315 and Leu320 at the C-terminal are critical for oligomerisation and UDP- or UDP-glucose binding. Gft3 homologs constitutes a unique subfamiliy of glycosyltransferases as they are highly conserved and only found in SRRP-containing bacteria .
D-allulose-6-phosphate 3-epimerase (AlluloseP_3_epimer_AlsE)
Type: Family

This entry represents D-allulose-6-phosphate 3-epimerase from bacteria, including AlsE from Escherichia coli. AlsE catalyses the reversible epimerization of D-allulose 6-phosphate to D-fructose 6-phosphate . Its structure has been solved .
Sulfopropanediol 3-dehydrogenase (Sulfopropanediol_dehydrog_HpsN)
Type: Family

This entry represents sulfopropanediol 3-dehydrogenase from Proteobacteria, including HpsN from Cupriavidus pinatubonensis. HpsN catalyses the NAD-dependent oxidation of (R)-2,3-dihydroxypropane-1-sulfonate to (R)-3-sulfolactate .
5-deoxyribose 1-phosphate isomerase (Deoxyribose1P_isomerase_DrdI)
Type: Family

This entry represents 5-deoxyribose 1-phosphate isomerase from bacteria, including DrdI from Bacillus thuringiensis serovar kurstaki. DrdI catalyzes the isomerization of 5-deoxy-alpha-D-ribose 1-phosphate to 5-deoxy-D-ribulose 1-phosphate, as part of a 5-deoxyribose salvage pathway that recycles this toxic radical SAM enzyme by-product to mainstream metabolites .
Tape measure protein (GpH_LAMBDA)
Type: Family

This entry represents tape measure proteins (TMPs) found in Siphoviridae . TMP is important for assembly of phage tails and involved in tail length determination . It serves as a ruler that controls the length of tail and is ejected from the tail prior to the DNA during DNA injection . Mutated forms of TMP cause tail fibres to be shortened .

This protein is also found in bacteria, suggesting prophage matches also occur.
Rqc2 homolog RqcH, archaeal (RqcH_archaeal)
Type: Family

Ribosome-associated protein quality control (RQC) sense ribosome stalling during translation and mediate subunit recycling and nascent-chain proteolysis. Rqc2 is one of the eukaryotic sense factors of ribosomal obstruction and recruits the E3 ligase Ltn1/Listerin for ubiquitination and proteasome degradation. When this mechanism fails, it adds a poly-Alanine chain to promote its destruction. Bacterial and archaeal homologues, namely RqcH add a poly-Ala chain to the aberrant nascent chain in the large ribosome subunit and tag it for degradation .

This entry represents the Rqc2 homologue (RqcH) from archaea.
Rqc2 homolog RqcH, bacterial (RqcH_bacterial)
Type: Family

Ribosome-associated protein quality control (RQC) sense ribosome stalling during translation and mediate subunit recycling and nascent-chain proteolysis. Rqc2 is one of the eukaryotic sense factors of ribosomal obstruction and recruits the E3 ligase Ltn1/Listerin for ubiquitination and proteasome degradation. When this mechanism fails, it adds a poly-Alanine chain to promote its destruction. Bacterial and archaeal homologues, namely RqcH add a poly-Ala chain to the aberrant nascent chain in the large ribosome subunit and tag it for degradation .

This entry represents the Rqc2 homologue (RqcH) from bacteria which is part of a process analogous and partial redundant to its canonical ssrA/tmRNA system.
Flavin-dependent monooxygenase TetX (TetX_monooxygenase)
Type: Family

The flavin-dependent monooxygenase TetX inactivates all known tetracyclines, as it interacts with the part of the molecule required for its action. It catalyses a monooxygenation step in which it hydroxylates carbon 11a from tetracyclins and allows further breakdown, non-enzymatically, to inactivate them . This enzyme is present in numerous pathogens of clinical importance, and confers tetracycline resistance to all generations of this antibiotic.
Ribosome protection protein VmlR (VmlR)
Type: Family

Some antibiotics bind to the large ribosomal subunit at the peptidyl-transferase centre (PTC) or adjacent to it, in the ribosomal exit tunnel. Gram-positive bacteria have antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F type (ABCF) that provide them resistance to that kind of antibiotics. These proteins are also found in some Gram-negative bacteria .

VmlR is a ribosomal protection protein that confers resistance to lincomycin (Lnc), the streptogramin A (SA) antibiotic virginiamycin M (VgM) and the pleuromutilin antibiotic tiamulin. It is an ABCF protein that binds to the E site of the antibiotic-stalled ribosomes inducing conformational changes in the P-site, and allows the dissociation of the antibiotic from its PTC binding site .
ATP-binding protein Uup (Uup)
Type: Family

Uup is an ATP-binding cassette (ABC) protein of the F type (ABCF). It has ATPase activity and possesses two nucleotide binding domains which comprise Walker A/B motifs connected by a linker and a coiled-coil C-terminal domain. It binds double-stranded DNA with no sequence specificity . The Uup ATPase activity functions cooperatively thus the inactivation of one site suppresses all ATP hydrolytic activity . It is implicated in precise excision of transposons. It bind to branched DNAs and is involved in resolution of branched DNA intermediates that result from template switching in post replication gaps .It may also be involved in the 50S ribosome subunit assembly due to its genetic interaction with translational GTPase BipA .
UDP-N-acetylmuramoyl-L-alanine--L-glutamate ligase MurD2 (MurD2)
Type: Family

The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria is comprised of a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages:

(1) formation of UDP-N-acetylmuramic acid (UDPMurNAc) from N-acetylglucosamine (GlcNAc).

(2) addition of a short polypeptide chain to the UDPMurNAc.

(3) addition of a second GlcNAc to the disaccharide-pentapeptide building block and transport of this unit through the cytoplasmic membrane and incorporation into the growing peptidoglycan layer.

Stage two involves four key Mur ligase enzymes: MurC (

) , MurD (

) , MurE (

) and MurF (

) . These four Mur ligases are responsible for the successive additions of L-alanine, D-glutamate, meso-diaminopimelate or L-lysine, and D-alanyl-D-alanine to UDP-N-acetylmuramic acid . All four Mur ligases are topologically similar to one another, even though they display low sequence identity. They are each composed of three domains: an N-terminal Rossmann-fold domain responsible for binding the UDPMurNAc substrate; a central domain (similar to ATP-binding domains of several ATPases and GTPases); and a C-terminal domain (similar to dihydrofolate reductase fold) that binds the incoming amino acid . Residues found in the three domains (the Asp50, Lys130 (GKT motif), and Glu174 residues, MurC numbering) are involved in the catalytic process . The conserved sequence motifs found in the four Mur enzymes also map to other members of the Mur ligase family, including folylpolyglutamate synthetase, cyanophycin synthetase and the capB enzyme from Bacillales .

This entry represents UDP-N-acetylmuramoylalanine-L-glutamate ligase (MurD2). MurD2 catalyses the addition of l-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine. This enzyme is present in some microorganisms that lack orthologues of Glu racemase or d-Glu aminotransferase, like Xanthomonas oryzae .
SAR-endolysin-like (SAR_endolysin-like)
Type: Family

Endolysin is a lysozyme that hydrolyses the (1->4)-beta-glycosidic linkage between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) residues in the bacterial cell wall peptidoglycan . Endolysin and the cell membrane pore-forming proteins holin and spanin act together to bring about host cell lysis and release of virus particles .

This family includes SAR-endolysins (signal-anchor-release endolysins) from bacteriophages and prophage lysozymes mostly from Proteobacteria.

Unlike T4 E phage lysozyme, the endolysin R21 from Enterobacteria phage P21 has an N-terminal SAR (signal-arrest-release) domain that anchors the endolysin to the membrane in an inactive form, which act to prevent premature lysis of the infected bacterium. The dsDNA phages of eubacteria use endolysins or muralytic enzymes in conjunction with hollin, a small membrane protein, to degrade the peptidoglycan found in bacterial cell walls . Similarly, prophage lysozymes containing the SAR domain facilitate the biosynthesis of its cell wall heteropolymer peptidoglycan and cell division in bacteria . These enzymes cleave the glycosidic beta 1,4-bonds between the N-acetylmuramic acid and the N-acetylglucosamine of the peptidoglycan .
UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-L-glutamate epimerase MurL (MurL)
Type: Family

This entry represents UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-L-glutamate epimerase (MurL) that catalyses the epimerisation of the terminal L-glutamate in UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-L-glutamate. It is present in microorganisms that lack orthologues of Glu racemase or d-Glu aminotransferase, such as Xanthomonas oryzae, and allow the biosynthesis of d-Glu together with MurD2, via an alternative pathway during the peptidoglycan biosynthesis .
N-acetyltransferase RimI (RimI)
Type: Family

This entry represents RimI, a GCN5-related N-acetyltransferase (GNAT) also known as [Ribosomal protein bS18]-alanine N-acetyltransferase which catalyses the acetylation of the N-terminal alanine of ribosomal protein bS18 . RimI can also acetylate an N-epsilon-lysine on different proteins which constitutes one of the most abundant and important post-translational modifications. This suggests that RimI has N-alpha-amino acid and N-epsilon-lysine acetylation activity, but the substrate specificity of this enzyme is still unclear .
Murein peptide amidase A (MpaA)
Type: Family

MpaA is a murein-tripeptide-specific zinc carboxypeptidase that hydrolyses the gamma-D-glutamyl-diaminopimelic acid bond in the murein tripeptide (L-Ala-gamma-D-Glu-meso-Dap), derived from the turnover of murein but it is not active against the murein tetrapeptide (L-Ala-gamma-D-Glu-meso-Dap-D-Ala). MpaA is a dimeric metalloprotein, containing one zinc ion per chain. Crystal structure studies revealed that this protein has high structural similarity to eukaryotic zinc carboxypeptidases and that it has a narrower substrate specificity due to an additional structure that partially occludes the substrate-binding groove . MpaA belongs to the peptidase M14 family.
Ubiquinone biosynthesis protein UbiU (UbiU)
Type: Family

This entry represents a group of bacterial proteins, including UbiU from Escherichia coli. UbiU is involved in the O2-independent ubiquinone (coenzyme Q) biosynthesis pathway alongside UbiV (YhbV), and UbiT (YhbT) .
Ubiquinone biosynthesis protein UbiV (UbiV)
Type: Family

This entry represents a group of bacterial proteins, including UbiV from Escherichia coli. UbiV is involved in the O2-independent ubiquinone (coenzyme Q) biosynthesis pathway alongside UbiU (YhbU), and UbiT (YhbT) .
N-acetylornithine carbamoyltransferase ArgF'-like (ArgF')
Type: Family

This entry represents a group of N-acetylornithine carbamoyltransferases mainly from Proteobacteria, including ArgF' from Xanthomonas campestris pv. campestris. ArgF' is invovled in an alternative arginine biosynthesis pathway. It catalyses the transfer of the carbamoyl group from carbamoyl phosphate to the δ-amino group of N2-acetyl-L-ornithine to produce N2-acetyl-L-citrulline .