SII-SWORD/CoKE huggingface dataset:
Tat proofreading chaperone DmsD (DmsD_chaperone)
Type: Family

DmsD is essential for the biogenesis/assembly of dimethyl sulfoxide (DMSO) reductase in Escherichia coli. DmsD binds the signal peptide of DmsA - the catalytic subunit of the DMSO reductase and a substrate for the Twin-arginine translocase (Tat) pathway - but it is not required for the interaction of the DmsA signal peptide with the Tat system . DmsD may be part of a chaperone cascade complex that facilitates a folding-maturation pathway for the substrate protein .
DNA topoisomerase I, type IA (Topoisom_1_IA)
Type: Family

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 .

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 .

This entry describes archaeal and bacterial-type topoisomerase I, which belongs to type 1A topoisomerases .
GDP-mannose mannosyl hydrolase, Enterobacteria (GDPMH_Gmm)
Type: Family

GDP-mannose mannosyl hydrolase (GDPMH, Gmm) from Escherichia coli hydrolyses both GDP-mannose and GDP-glucose . GDPMH is a member of the Nudix family of enzymes, but unlike other Nudix enzymes GDPMH catalyses the hydrolysis of nucleoside diphosphate derivatives by nucleophilic substitution at carbon, rather than at phosphorus. Thus, these enzymes are sugar nucleotide hydrolases rather than pyrophosphatases . GDPMH could participate in the regulation of cell wall biosynthesis by influencing the concentration of GDP-mannose or GDP-glucose in the cell and might also be involved in the biosynthesis of the slime polysaccharide colanic acid .
GDP-L-fucose synthase/GDP-L-colitose synthase (GDP_fucose/colitose_synth)
Type: Family

GDP-L-fucose synthase is responsible for the last step of the major metabolic pathway resulting in GDP-L-fucose synthesis from GDP-D-mannose. It catalyses a combined epimerase and NADPH-dependent reductase reaction, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose . Since several cell-surface antigens, including the leukocyte Lewis system and cell-surface antigens in pathogenic bacteria, depend on the availability of GDP-L-fucose for their expression, the enzyme is a potential target for therapy in pathological states depending on selectin-mediated cell-to-cell interactions .

This entry also includes ColC from Yersinia pseudotuberculosis. ColC is a GDP-L-colitose synthase, which is a bifunctional enzyme catalysaing the C-5 epimerization of GDP-4-keto-3,6-dideoxy-D-mannose and the subsequent C-4 keto reduction of the resulting L-epimer to give GDP-L-colitose .
Maleate isomerase (Maleate_isomerase)
Type: Family

Maleate isomerase catalyses the conversion of maleate to fumarate . In Pseudomonas putida, maleate isomerase (maiA or nicE) is involved in the aerobic nicotinate degradation pathway .
Regulator of RpoS (RssB)
Type: Family

SigmaS (RpoS) is the master regulator of the general stress response in Escherichia coli. RssB regulates the turnover of RpoS by promoting its proteolysis in exponentially growing cells . RssB also has a second function in the control of mRNA polyadenylation and degradation .
RNA polymerase sigma factor FliA (Sigma70_FliA)
Type: Family

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .

RNA polymerase sigma factor FliA controls the expression of flagella-related genes and may regulate the expression of genes involved in virulence .
ATP-dependent RNA helicase DeaD (DEAD_helicase_DeaD)
Type: Family

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, such as splicing, RNA transport, ribosome biogenesis, translation and RNA decay. They are enzymes that unwind double-stranded RNA molecules in an energy dependent fashion through the hydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) of helicases. As other SF1 and SF2 members they contain seven conserved motifs which are characteristic of these two superfamilies . DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-binding aspartic acid).
ATP-dependent RNA helicase DbpA (DEAD_helicase_DbpA)
Type: Family

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, such as splicing, RNA transport, ribosome biogenesis, translation and RNA decay. They are enzymes that unwind double-stranded RNA molecules in an energy dependent fashion through the hydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) of helicases. As other SF1 and SF2 members they contain seven conserved motifs which are characteristic of these two superfamilies . DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-binding aspartic acid).

The RNA helicase DbpA has an RNA-dependent ATPase activity, which is specific for 23S rRNA . It is involved in assembly of the 50S ribosomal subunit .
ATP-dependent RNA helicase SrmB (DEAD_helicase_SrmB)
Type: Family

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, such as splicing, RNA transport, ribosome biogenesis, translation and RNA decay. They are enzymes that unwind double-stranded RNA molecules in an energy dependent fashion through the hydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) of helicases. As other SF1 and SF2 members they contain seven conserved motifs which are characteristic of these two superfamilies . DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-binding aspartic acid).

SrmB is a DEAD-box RNA helicase that is involved in ribosome assembly. Deletion of the srmB gene in Escherichia coli causes a slow-growth phenotype at low temperature .
ATP-dependent RNA helicase RhlE (DEAD_helicase_RhlE)
Type: Family

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, such as splicing, RNA transport, ribosome biogenesis, translation and RNA decay. They are enzymes that unwind double-stranded RNA molecules in an energy dependent fashion through the hydrolysis of NTP. DEAD-box RNA helicases belong to superfamily 2 (SF2) of helicases. As other SF1 and SF2 members they contain seven conserved motifs which are characteristic of these two superfamilies . DEAD-box is named after the amino acids of motif II or Walker B (Mg2+-binding aspartic acid).

RhlE is a DEAD-box RNA helicase that is involved in ribosome assembly. It may play a role in the interconversion of ribosomal RNA-folding intermediates that are further processed by DeaD or SrmB during ribosome maturation .
HNS-dependent expression B (HdeB)
Type: Family

HNS (histone-like nucleoid structuring)-dependent expression A (HdeA) protein is a stress response protein found in highly acid resistant bacteria such as Shigella flexneri and Escherichia coli, but which is lacking in mildly acid tolerant bacteria such as Salmonella . HdeA is one of the most abundant proteins found in the periplasmic space of E. coli, where it is one of a network of proteins that confer an acid resistance phenotype essential for the pathogenesis of enteric bacteria . HdeA is thought to act as a chaperone, functioning to prevent the aggregation of periplasmic proteins denatured under acidic conditions. The HNS protein, a chromatin-associated protein that influences the gene expression of several environmentally-induced target genes, represses the expression of HdeA. HdeB, which is encoded within the same operon, may form heterodimers with HdeA. HdeA is a single domain α-helical protein with an overall fold that is similar to the fold of the N-terminal subdomain of the GluRS anticodon-binding domain.

This entry represents acid stress chaperone HdeB .
Transcription elongation factor GreA/GreB (Tscrpt_elong_fac_GreA/B)
Type: Family

Bacterial proteins GreA and GreB are necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. Arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked DNA/RNA/ polymerase ternary complexes. Cleavage of the nascent transcript by cleavage factors, such as GreA or GreB, allows the resumption of elongation from the new 3' terminus . Escherichia coli GreA and GreB are sequence homologues and have homologues in every known bacterial genome . GreA induces cleavage two or three nucleotides behind the terminus and can only prevent the formation of arrested complexes while greB releases longer sequences up to eighteen nucleotides in length and can rescue preexisting arrested complexes. These functional differences correlate with a distinctive structural feature, the distribution of positively charged residues on one face of the N-terminal coiled coil. Remarkably, despite close functional similarity, the prokaryotic Gre factors have no sequence or structural similarity with eukaryotic TFIIS.
Regulator of nucleoside diphosphate kinase (Rnk)
Type: Family

Regulator of nucleoside diphosphate kinase (Rnk) is a RNA polymerase-interacting protein that shares high sequence similarity with the C-terminal domains of the Gre factors (GreA and GreB) and the Thermus/Deinococcus anti-Gre factor Gfh1 . Rnk has been shown to regulate the levels of the nucleoside diphosphate kinase Ndk . It also has been shown to compete with the Gre factors for binding to RNA polymerase, and may therefore have a role as an anti-Gre factor .
Ribosomal protein eS28 conserved site (Ribosomal_eS28_CS)
Type: Conserved_site

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. One of these families consists of:

Mammalian S28 .

Plant S28 .

Fungi S33 .

Archaebacterial S28e.

These proteins have from 64 to 78 amino acids. This entry represents a highly conserved nonapeptide from the C-terminal extremity of these proteins.

NOTE: This entry matches

, which is a translation initiation factor IF-2. This is a false positive.
Acylphosphatase, bacteria (Acylphosphatase_bac)
Type: Family

Acylphosphatase (

) is an enzyme of approximately 98 amino acid residues that specifically catalyses the hydrolysis of the carboxyl-phosphate bond of acylphosphates , its substrates including 1,3-diphosphoglycerate and carbamyl phosphate . The enzyme has a mainly β-sheet structure with 2 short α-helical segments. It is distributed in a tissue-specific manner in a wide variety of species, although its physiological role is as yet unknown : it may, however, play a part in the regulation of the glycolytic pathway and pyrimidine biosynthesis . There are two known isozymes. One seems to be specific to muscular tissues, the other, called 'organ-common type', is found in many different tissues. A number of bacterial and archebacterial hypothetical proteins are highly similar to that enzyme and that probably possess the same activity.

This entry represents bacteria acylphosphatase.
Sirtuin, class U (Sirtuin_class_U)
Type: Family

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

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

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

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

The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains .

This entry represents the class U sirtuins.
CRISPR-associated endonuclease Cas9 (Cas9)
Type: Family

CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA) to guide the silencing of invading nucleic acids. In type II CRISPR systems, correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and this protein, Cas9 (Csn1) . The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Subsequently Cas9/crRNA/tracrRNA endonucleolytically cleaves linear or circular dsDNA target complementary to the spacer . Cas9 probably recognises a short motif in the CRISPR repeat sequences (the PAM or protospacer adjacent motif) to help distinguish self versus nonself.
RNA polymerase sigma factor RpoD (Sigma70_RpoD)
Type: Family

Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Sigma factor RpoD, sometimes known as SigA, is the primary sigma factor during exponential growth .
Adrenocortical dysplasia protein (ACD)
Type: Family

Adrenocortical dysplasia protein (acd, also known as TPP1) is a component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways . It also forms a heterodimer with POT1 that increases the activity and processivity of the telomerase core enzyme .

This entry also includes fission yeast TPP1 homologue, Tpz1. Together with Pot1 it forms a complex that protects telomeres and regulates telomere length .
Protein RCC2 (RCC2)
Type: Family

Protein RCC2 (also known as TD-60) interacts with microtubules and is required for completion of mitosis and cytokinesis . It may function as a guanine nucleotide exchange factor for the small GTPase RAC1 .

This entry also includes some uncharacterised bacterial proteins.
Inhibitor of growth protein 1, PHD-type zinc finger (ING1_PHD_Znf)
Type: Domain

Members of the ING (inhibitor of growth protein) family of tumour suppressors regulate cell cycle progression, apoptosis, and DNA repair as important cofactors of p53. Inhibitor of growth protein 1 (ING1) is the best characterised member of this family of five genes (ING1-5) with conserved plant homeodomains (PHDs) .

ING1 interacts with proliferating cell nuclear antigen (PCNA) and PCNA-interacting protein p15 (PAF) . p53 and ING1 have been shown to functionally cooperate in the activation of apoptosis . ING1 could also induce apoptosis by translocation from the nucleus to the mitochondria where interaction with BAX stabilises this protein, promoting its pro-apoptotic function . ING1 functions in DNA demethylation and has a role in the early steps of multiple DNA repair pathways .

This entry represents the C-terminal plant homeodomain (PHD)-type zinc-finger domain of ING1.
Sorting nexin-30, BAR domain (SNX30_BAR)
Type: Domain

Sorting nexin-30 (SNX30) contains a PX (phox homology) domain and belongs to the sorting nexin family. It may be involved in several stages of intracellular trafficking .

This entry represents the C-terminal Bin/Amphiphysin/Rvs (BAR) domain of SNX30.
ING family (ING_fam)
Type: Family

This family of chromatin modification proteins are involved in the regulation of cell cycle progression, apoptosis, and DNA repair. Members are found in yeast, animals and plants. They share significant sequence in their C-terminal regions containing PHD finger domains, which have been implicated in chromatin-mediated transcriptional regulation . The family includes proteins YNG1, YNG2 and Pho23 from Saccharomyces cerevisiae , png1 and png2 from Schizosaccharomyces pombe , inhibitor of growth proteins ING1-5 from mammals , and Arabidopsis homologues ING1 (At3g24010) and ING2 (At1g54390) .
Sorting nexin-5, BAR domain (BAR_SNX5)
Type: Domain

Sorting nexin-5 (SNX5) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides . SNX5 also contains a BAR domain that is C terminus to the PX domain. Besides being involved in several stages of intracellular trafficking, SNX5 also plays a role in macropinocytosis and in the internalisation of EGFR after EGF stimulation . This entry represents the BAR domain.
Sorting nexin-6, BAR domain (BAR_SNX6)
Type: Domain

Sorting nexins (SNXs) are a diverse group of cellular trafficking proteins that are unified by the presence of a phospholipid-binding motif, the PX domain. The ability of these proteins to bind specific phospholipids, as well as their propensity to form protein-protein complexes, points to a role for these proteins in membrane trafficking and protein sorting .

SNX6 was found to interact with members of the transforming growth factor-beta family of receptor serine/threonine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. SNX6 forms a stable complex with SNX1 and may be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p . It also plays roles in enhancing the degradation of EGFR and in regulating the activity of Na,K-ATPase through its interaction with Translationally Controlled Tumor Protein (TCTP) . SNX6 is localized in the cytoplasm where it is thought to target proteins to the trans-Golgi network . In addition, SNX6 was found to be translocated from the cytoplasm to nucleus by Pim-1, an oncogene product of serine/threonine kinase. This translocation is not affected by Pim-1-dependent phosphorylation, but the functional significance is unknown .

BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. This entry represents the BAR domain is SNX6.
Sorting nexin-1, BAR domain (SNX1_BAR)
Type: Domain

Sorting nexin-1 (SNX1) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain (

) that is responsible for binding to specific phosphoinositides . SNX1 and SNX2 are orthologues of yeast Vps5, which is a component of retromer complex that is essential in endosome-to-Golgi retrograde transport .

The mammalian retromer complex is composed of the SNX1/SNX2 alternative heterodimer or homodimer and the Vps26-Vps29-Vps35 obligate heterotrimer . Like SNX2, SNX1 also has an additional C-terminal BAR domain. SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function .

SNX1 may have a role in sensing membrane curvature and inducing the formation of tubules .

This entry represents the Bin/Amphiphysin/Rvs (BAR) domain of SNX1. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.
Vacuolar protein sorting-associated protein 29 (Vps29)
Type: Family

This entry represents Vacuolar protein sorting-associated 29 (Vps29) from animals, yeasts and plants. Vps29 is an essential component of the retromer complex, a conserved complex required in endosome-to-Golgi retrograde transport .
Sorting nexin-8/Mvp1 (SNX8/Mvp1)
Type: Family

Sorting nexin-8 (SNX8) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides . It may play a role in intracellular protein transport from early endosomes to the trans-Golgi network . SNX8 yeast counterpart, Mvp1, is required for sorting proteins to the vacuole .