SII-SWORD/CoKE huggingface dataset:
Copper amine oxidase, copper-binding site (Cu_Am_Ox_Cu-bd)
Type: Conserved_site

Copper-containing Amine oxidase (AO) is found in bacteria, fungi, plants and animals, it is an homodimeric enzyme that binds one copper ion per subunit as well as a 2,4,5-trihydroxyphenylalanine quinone (or topaquinone) (TPQ) cofactor. This cofactor is derived from a tyrosine residue. This entry represents the copper-binding site which contains the histidines that bind the copper atom .

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .
Copper amine oxidase, TPQ-binding site (Cu_Am_ox_TPQ-bd)
Type: Conserved_site

Copper-containing Amine oxidase (AO) is found in bacteria, fungi, plants and animals, it is an homodimeric enzyme that binds one copper ion per subunit as well as a 2,4,5-trihydroxyphenylalanine quinone (or topaquinone) (TPQ) cofactor. This entry represents a conserved site that contains the tyrosine which give rises to the TPQ cofactor .

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .
Nickel storage protein Hpn (Hpn-like)
Type: Family

This entry represents Hpn protein found in different strains of Helicobacter pylori . Hpn is a histidine-rich polypeptide, 60 amino acids in length, capable of binding nickel and several other metals. It can store a reserve of nickel for biosynthesis of active urease, critical to the ability of the bacterium to survive acid exposure during colonisation, and hydrogenase . Hpn is closely related in its N-terminal region to a somewhat longer His and Gln-rich protein, called the Hpn-like protein. Both are expressed, under control of NikR, in response to nickel.
8-methylmenaquinol:fumarate reductase membrane anchor subunit (SdhE)
Type: Family

This entry represents the membrane anchor subunit (SdhE) of 8-methylmenaquinol:fumarate reductase (MFR), that catalyses the reduction of fumarate using 8-methylmenaquinol-6 as electron donor. The MFR complex is composed of three subunits: a flavoprotein (SdhA), an iron-sulfur protein (SdhB), and one hydrophobic anchor protein (represented by this entry) . The MFR complex has no succinate oxidation activity and is involved in anaerobic metabolism. SdhE contains a striking cysteine-rich region referred to as 10-cysteine motif. This protein is predicted to contain no transmembrane domains and its association with the membrane is most likely mediated via amphipathic helices .
Phospholipase D-like domain-containing anti-phage protein (PhospholipD-like_anti-phage)
Type: Family

Proteins included in this family are components of the restriction-like anti-phage system . Members of this prokaryotic family contain a phospholipase D-like domain at the N terminus and a helicase domain at the C terminus.
Anti-phage-associated (Antiphage_assoc)
Type: Family

This entry represents a family of prokaryotic proteins that are associated with the restriction-like anti-phage system. Most members of this group contain the domain

. The role of this proteins in the anti-phage system is not fully understood .
Anti-phage ATPase IteA-like (IteA-like)
Type: Family

Proteins of this family are the ATPase components of the IteAS anti-phage system, which consists of an ATPase (IteA) and a protease (IteS) .
Anti-phage peptidase IteS-like (IteS-like)
Type: Family

This entry represents the Anti-phage peptidase IteS. Proteins of this family are the protease components of the IteAS anti-phage system, which consists of an ATPase (IteA) and a protease (IteS) .
Acetoacetyl-CoA reductase PhaB, cyanobacteria (PhaB)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Acetoacetyl-CoA reductase from Synechocystis sp. (PhaB), which catalyses the reduction of acetoacetyl-CoA to (R)-3-hydroxybutyryl-CoA .
Acetoacetyl-CoA reductase PhaA, cyanobacteria (PhaA)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Acetoacetyl-CoA reductase from Synechocystis sp. (PhaA).
MAP_0585-like (MAP_0585-like)
Type: Family

This entry represents a group of proteins from mycobacteria, including MAP_0585 from Mycolicibacterium paratuberculosis (

). Members of this family average about 310 amino acids in length, including a signal peptide-containing N-terminal region of about 30 amino acids, a conserved C-terminal region of about 130 amino acids, and a central intrinsically disordered region of about 150 amino acids, rich in Pro, Gly, and hydrophilic residues. The protein has been studied as a vaccine component but is otherwise uncharacterised .
SpoV, N-terminal (SpoV_N)
Type: Domain

This entry represents a domain found at the N-terminal of a group of proteins from Streptococcus pyogenes (Group A Streptotoccus), including SpyM3_0132 (

), named SpoV (streptococcal peptide controlling virulence), and tandem proteins Spy0169 and SPy0170. The N-terminal region is well conserved among members of this family, while C-terminal regions may be unrelated .
ThiI, N-terminal (ThiI_N)
Type: Domain

This entry covers the THUMP and AANH domains found at the N terminus of ThiI proteins.

tRNA sulfurtransferase ThiI catalyses the ATP-dependent transfer of a sulfur to tRNA to produce 4-thiouridine in position 8 of tRNAs, which functions as a near-UV photosensor . In some bacteria, ThiI is a bifunctional enzyme required for the synthesis of both the 4-thiouridine modification in tRNA and the thiazole moiety in the thiamine biosynthesis pathway .

Three domains of ThiI are essential for the thiolation of tRNA: a THUMP domain that binds tRNA (see

) , an AANH domain (

) that activates the uridine residue by adenylylation , and a rhodanese-like domain (

) that transfers sulfur to the activated uridine residue . Neither the THUMP nor the AANH domain of ThiI are essential for thiamine synthesis, only the rhodanese domain is necessary for synthesis of the thiazole moiety of thiamine .
ThiI, THUMP domain (THUMP_ThiI)
Type: Domain

This entry represents the THUMP domain found at the N terminus of ThiI, which has been implicated in the recognition of the acceptor-stem region. The THUMP domain is named after thiouridine synthases, methylases and PSUSs. The domain consists of about 110 amino acid residues. It is predicted to be an RNA-binding domain and probably functions by delivering a variety of RNA modification enzymes to their targets.

tRNA sulfurtransferase ThiI catalyses the ATP-dependent transfer of a sulfur to tRNA to produce 4-thiouridine in position 8 of tRNAs, which functions as a near-UV photosensor . In some bacteria, ThiI is a bifunctional enzyme required for the synthesis of both the 4-thiouridine modification in tRNA and the thiazole moiety in the thiamine biosynthesis pathway .

Three domains of ThiI are essential for the thiolation of tRNA: a THUMP domain that binds tRNA (see

) , an AANH domain (

) that activates the uridine residue by adenylylation , and a rhodanese-like domain (

) that transfers sulfur to the activated uridine residue . Neither the THUMP nor the AANH domain of ThiI are essential for thiamine synthesis, only the rhodanese domain is necessary for synthesis of the thiazole moiety of thiamine .
Anti-phage protein Ppl (Ppl_antiphage)
Type: Family

This entry represents a group of uncharacterised proteins from gammaproteobacteria. Members of this family exhibited anti-phage activities . They contain a PHP-like (Polymerase and Histidinol Phosphatase) domain (

) and a P-loop NTPase domain (

).
Sialidase A repeat (NanA_rpt)
Type: Repeat

This entry represents two tandem copies of a typically 17-amino acid repeat with a characteristic EXPEF or EXPEY motif, found mostly in surface-bound glycoside or peptide hydrolases with LPXTG motifs for covalent anchoring on the cell wall from firmicutes. It occurs in the C-terminal region of the Sialidase A from Streptococcus pneumoniae (NanA), where this region is not described as either catalytic or carbohydrate-binding, but instead as P/G/S/T-rich and repeat-containing . Multiple copies of the repeat occur also in the IgA1 protease ZmpD, another Streptococcus pneumoniae virulence factor .
Anti-phage protein Upx-like (Upx-like)
Type: Family

Proteins members of this family exhibit anti-phage activities .
Dot/Icm T4SS effector LegC2/C7 (T4SS_LegC2C7)
Type: Family

This entry represents a group of proteins that form part of the Dot/Icm type IV secretion system (T4SS) from Legionellales, including YlfA/LegC7 (

) and YlfB/LegC2 (

), which were initially identified in a screen for proteins that cause growth inhibition in yeast and functionally mimic glutamine (Q)-SNARE proteins. Members of this family are probably membrane-associated effectors that enhance remodeling of the bacteria-containing vacuole by promoting association and possibly fusion of ER-derived membrane vesicles .
Membrane protein NGO_0222-like (NGO_0222-like)
Type: Family

Members of this family, which includes NGO_0222 from Neisseria gonorrhoeae (

), are small membrane proteins found in multiple species from Neisseriaceae .
Dot/Icm T4SS effector AnkD/LegA15 (T4SS_AnkD)
Type: Family

This entry represents a group of proteins from Legionellales, including the ankyrin repeat-containing protein LegA15 (AnkD,

) from Legionella pneumophila, which shows structural similarity to another effector, LegA3/AnkH (

). This protein contains a cysteine protease-like (CPL) domain with similarity to ubiquitin-like hydrolases .
Dot/Icm T4SS effector AnkH/LegA3 (T4SS_AnkH)
Type: Family

This entry represents a group of proteins from Legionellales, including the ankyrin repeat-containing protein LegA3 (also known as AnkH,

) from Legionella pneumophila, which shows structural similarity to another effector, LegA15/AnkD, which contains a cysteine protease-like (CPL) domain with similarity to ubiquitin-like hydrolases . AnkH interacts with the host nuclear protein La-related protein 7 (LARP7), which is a component of the 7SK small nuclear ribonucleoprotein (snRNP) complex, interfering with with transcriptional elongation by polymerase (Pol) II, leading to host global transcriptional reprogramming .
Amuc_1102-like (Amuc_1102-like)
Type: Family

This entry represents the pilus-like protein Amuc_1102 from Akkermansia muciniphila (

) and similar bacterial sequences . Members of this family are thought to be structural and assembly proteins for a pilus-like structure similar to some archaeal type IV pili. The crystal structure of Amuc_1102 revealed an immunoglobulin-like fold .
CLC_0170-like (CLC_0170-like)
Type: Family

Members of this family are related to Clostridium botulinum protein CLC_0170 and are found in endospore-forming Gram-positive species. They average about 65 amino acids in length and contain extensively hydrophobic regions. These proteins are predicted to form an α-helical hairpin.
Dot/Icm T4SS effector AnkK/LegA5 (T4SS_AnkK)
Type: Family

This entry represents a group of proteins from Legionellales, including the ankyrin repeat-containing protein LegA5 (AnkK) from Legionella pneumophila .
STY0301-like (STY0301-like)
Type: Family

This entry represents the Cytoplasmic protein STY0301 from Salmonella typhi (

) and similar sequences mainly found in proteobacteria. Members of this highly divergent protein family average about 135 amino acids in length. Near-invariant residues or motifs include CP, GxP, LxP, CxY, and two additional Cys residues. These cysteines are predicted to form disulfide bonds. The function is unknown.
Amuc_1099-like (Amuc_1099-like)
Type: Family

This family represents uncharacterised proteins found mainly in Verrucomicrobiota, including Amuc_1099 from Akkermansia muciniphila (

).
SAV_915-like domain (SAV_915-like_dom)
Type: Domain

This entry represents a domain found in uncharacterised proteins from Actinomycetes, including SAV_915 from the paulomycin biosynthetic gene cluster (BGC) of Streptomyces paulus . Some members of this group have two separated copies of the domain.
TIR domain-containing anti-phage reverse transcriptase (Retron_TIR_antiphage)
Type: Family

This entry represents a group of anti-phage reverse transcriptases from enterobacterales. Proteins of this family have a TIR domain (

) in the C terminus.
SIR2-like anti-phage-associated protein (SIR2-like_antiphage-assoc)
Type: Family

Proteins of this family are associated with an anti-phage system, which has been widely identified in bacterial and archaeal genomes .
SCO6880-like (SCO6880-like)
Type: Family

This entry represents a group of uncharacterised proteins from Actinomycetes, including SCO6880 from Streptomyces coelicolor (

).
Cysteine-responsive attenuator conserved region, actinomycetes (Cys_resp_CS_actino)
Type: Conserved_site

This entry represents a conserved region of polycysteine-encoding leaderless short ORFs from Actinomycetes, which act as cysteine-responsive attenuators of operonic gene expression . It is often found towards the C-terminal end of the proteins.
Leukotriene A4 hydrolase-like, catalytic domain (LTA4H_cat)
Type: Domain

This entry represents the N-terminal catalytic domain of leukotriene A4 hydrolase (LTA4H;

) and close homologues such as cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase, ColAP), which are members of the aminopeptidase M1 family .

LTA4H is a bifunctional enzyme, possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is poorly understood while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals . It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives . The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase . Thermodynamic characterisation using different biophysical methods shows that structurally distinct inhibitors of the LTA4H occupy different regions of the binding site; while some (RB202, ARM1 and SC57461A) bind to the hydrophobic hydrolase side, both bestatin and captopril are located at the hydrophilic peptidase side .

LTB4H overexpression is associated with different pathological conditions and diseases such as cystic fibrosis, coronary heart disease, sepsis, shock, connective tissue disease, and chronic obstructive pulmonary disease. It is also overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well-known red wine polyphenolic compound with cancer chemopreventive activity .
Surface-associated protein SPy_0802-like (SPy_0802-like)
Type: Family

This entry represents a group of proteins from firmicutes, including SPy_0802 from Streptococcus pyogenes (

), which has been called a virulence factor capable of binding host red blood cells to block immune response by white cells, and was named S protein . Members of this family average about 170 amino acids in length, and often include a C-terminal region Lysin Motif domain (LysM,

), a peptidoglycan-binding domain for surface-associated proteins.
EF0163-like (EF0163-like)
Type: Family

This entry represents a group of predicted lipoproteins from lactobacillales, including EF0163 from Enterococcus faecalis (

), which was found to be upregulated more than six-fold in a mice peritonitis model . Many members of this family have an N-terminal lipoprotein signal peptide-like region, followed by a nearly 50 amino acid stretch rich in Glu, Asp, Gln, Asn, Ser, and Thr, and average about 170 amino acids in length.
Dot/Icm T4SS effector Ceg17 (T4SS_Ceg17)
Type: Family

This entry represents a group of proteins from Legionellales, including the Dot/Icm T4SS effector Ceg17 (

) from Legionella pneumophila .
Dot/Icm T4SS effector Ceg19 (T4SS_Ceg19)
Type: Family

This entry represents a group of proteins from Legionella spp., including the Dot/Icm T4SS effector Ceg19 (lpg1121,

) from Legionella pneumophila .
Dot/Icm T4SS effector Ceg9 (T4SS_Ceg9)
Type: Family

This entry represents a small group of proteins from Legionella spp., including the Dot/Icm T4SS effector Ceg9 (lpg0246,

) from Legionella pneumophila . Ceg9 interacts with isoforms of host reticulon 4 (Rtn4), a protein that regulates ER tubule formation .
Dot/Icm T4SS effector kinase LegK1 (T4SS_LegK1)
Type: Family

This entry represents a group of proteins from Legionella spp., including the Dot/Icm T4SS effector LegK1 (

) from Legionella pneumophila .
Dot/Icm T4SS effector Ceg32/SidI (T4SS_Ceg32)
Type: Family

This entry represents a group of proteins from Legionella sp., including the Dot/Icm T4SS effector Ceg32 (also known as SidI,

) from Legionella pneumophila . The N-terminal region of this protein, which contains a glucosyl transferase (GT) domain, is sufficient for direct binding of the putative target eEF1A .
Dot/Icm T4SS effector VpdC (T4SS_VpdC)
Type: Family

This entry represents a group of proteins from Legionellales, including the Dot/Icm T4SS effector VpdC (lpg1426,

) from Legionella pneumophila . VpdC converts phospholipids into lysophospholipids and plays an important role in vacuolar expansion .
Dot/Icm T4SS effector Ceg14/SidL (T4SS_Ceg14)
Type: Family

This entry represents a group of proteins from Legionella sp., including the Dot/Icm T4SS effector Ceg14 (also known as SidL,

) from Legionella pneumophila . Profilin, a protein involved in cytoskeletal structure in eukaryotes, suppresses the toxicity of Ceg14, which co-sediments with filamentous actin and inhibits actin polymerization in its presence .
Dot/Icm T4SS effector Ceg10 (T4SS_Ceg10)
Type: Family

This entry represents a group of proteins from Legionellales, including the Dot/Icm T4SS effector Ceg10 (lpg0284,

) from Legionella pneumophila .
Dot/Icm T4SS effector Lem8 (T4SS_Lem8)
Type: Family

This entry represents a group of proteins from Legionella sp., including the Dot/Icm T4SS effector Lem8 (lpg1290,

) from Legionella pneumophila . The Pleckstrin homology-like domain-containing protein Phldb2 involved in cytoskeleton organization is a target of Lem8, which plays a role in the inhibition of host cell migration .
Dibenzothiophene monooxygenase (DszC)
Type: Family

This entry includes dibenzothiophene monooxygenase from Rhodococcus erythropolis (DszC) and similar sequences mainly found in actinomycetes. DszC catalyses the first step of the '4S' desulphurisation pathway that removes covalently bound sulphur from dibenzothiophene (DBT) without breaking carbon-carbon bonds . This protein is organised into three regions: the N- and C-terminal regions are mainly α-helices packing together, whereas the middle region is folded into a β-sheet barrel .
PncF-like (PncF-like)
Type: Family

This entry represents a family that includes putative bacteriocins, immunity, and export proteins from Streptococcus, including PncF from Streptococcus pneumoniae (

) .
HK97-fold major capsid protein Staley_37-like (Staley_37-like)
Type: Family

This entry represents capsid proteins found in tailed bacteriophages and bacterial prophages, including Staley_37 from the Bacillus phage Staley (

). They share the same fold of the capsid protein as bacteriophage HK97, a virus that infects bacteria. Members of this family (

) use different numbers of the capsid protein to build capsids of different sizes .
Major capsid protein, mycobacteria-type (Capsid_mycobact-type)
Type: Family

This entry represents capsid proteins found mainly in bacteriophages and prophages mainly found in mycobacteriales.
Plasmid replication protein Slr7037-like (Slr7037-like)
Type: Family

Members of this family, including Slr7037 (CyRepA1,

) from the phage defence plasmid pSYSA of Synechocystis sp. PCC 6803, are plasmid replication proteins that share similarity to herpesvirus origin of replication binding protein (

).
Type IV pilus outer membrane protein Amuc_1098-like (Amuc_1098-like)
Type: Family

This entry represents Amuc_1098 from Akkermansia muciniphila (

) and related proteins from Verrucomicrobiota. Amuc_1098 is one of the most highly expressed outer membrane proteins in Akkermansia species. It is a full-length homologue of GspD from type II secretion systems (T2SS) and of the type IV pilus secretin PilQ. It belongs to a five protein type IV pilus-like system, Amuc_1098 to Amuc_1102 .