SII-SWORD/CoKE huggingface dataset:
Conserved hypothetical protein CHP02284 (CHP02284)
Type: Family

This entry represents a family of uncharacterised proteins predominantly found in bacteria that includes DUF2383 domain-containing protein from Pseudomonas aeruginosa (

). This protein shows a ferritin-like topology with a four-helix-bundle fold that lacks metal-ion-binding site typical of the ferritin family but has a potential metal-binding site . Its function is still unknown.
Conserved hypothetical protein CHP02285 (CHP02285)
Type: Family

Members of this family are found in several Proteobacteria, including Pseudomonas putida (strain KT2440), Bdellovibrio bacteriovorus HD100 (three members), Aeromonas hydrophila, and Chromobacterium violaceum ATCC 12472. The function is unknown.
Phenylacetic acid degradation protein PaaD (PaaD)
Type: Family

This members of this family belong to the thioesterase superfamily

, and are nearly always found adjacent to other genes of the phenylacetic acid degradation pathway . Their function is currently unknown, but a role as thioesterases is suggested.
Phenylacetic acid degradation protein PaaY (PaaY)
Type: Family

Members of this family are located next to other genes organised into apparent operons for phenylacetic acid degradation . PaaY is located near the end of these gene clusters and often next to PaaX, a transcriptional regulator. PaaY has a thioesterase activity involved in the efficient growth in phenylacetic acid which is responsible for the degradation of aromatic compounds in bacteria .
Phenylacetic acid degradation protein PaaN2 (PaaN_2)
Type: Family

This enzyme is proposed to act in the ring-opening step of phenylacetic acid degradation which follows ligation of the acid with coenzyme A (by PaaF) and hydroxylation by a multicomponent non-heme iron hydroxylase complex (PaaGHIJK). Gene symbols have been standardized in . This enzyme is related to aldehyde dehydrogenase family. This family includes sequences from Burkholderia, Bordetella, Streptomyces. Other PaaN enzymes are represented by a separate entry,

.
Peptidase M3B, oligoendopeptidase-related (Pept_M3B_oligopep-rel)
Type: Family

This family consists of probable oligoendopeptidases belonging to MEROPS peptidase family M3, subfamily M3B (clan MA(E)). The family is related to lactococcal PepF and group B streptococcal PepB (

) but in a distinct clade with considerable sequence differences not only to

but also to

. Likely substrates are small peptides and not whole proteins, as with PepF, but members are not characterised and the activity profile may differ. Several bacteria have both a member of this family and a member of the PepF family.
Peptidase M3B, oligoendopeptidase-related clade 3 (Pept_M3B_clade3)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This family consists of probable oligoendopeptidases belonging to MEROPS peptidase family M3, subfamily M3B (clan MA(E)). It is related to lactococcal PepF and group B streptococcal PepB (

) but in a distinct clade with considerable sequence differences not only to

but also to

. Members are not characterised with respect to their substrates and the activity profile may differ.
YgfB-like (YgfB-like)
Type: Family

This group of proteins includes the Escherichia coli proteins YgfB and YecA, and similar proteins mainly found in gammaproteobacteria. The function of these proteins is unknown. The crystal structure is known for the member from Haemophilus influenzae YgfB (

), which folds into seven α-helices arranged into two domains: a four-helix bundle and a three-helix up-down bundle .
Antitoxin Xre (Antitox_Xre)
Type: Family

Proteins in this family are found predominantly in the Proteobacteria. Antitoxin Xre is part of a type II toxin-antitoxin (TA) system. RES toxin inhibits the cell growth in E. coli, Xre neutralises the RES toxicity .
Metal-staphylopine-binding protein CntA-like (CntA-like)
Type: Family

This entry represents Metal-staphylopine-binding protein CntA from Staphylococcus aureus . CntA is involved in the import of divalent metals ions such as nickel, cobalt and zinc. It binds the metal via the metallophore StP, and transfers the StP-metal complex to the membrane-bound permease .

The ATP-binding cassette (ABC) type nickel transport system is comprised of five subunits NikABCDE: the two pore-forming integral inner membrane proteins NikB and NikC; the two inner membrane-associated proteins with ATPase activity NikD and NikE; and the periplasmic nickel binding NikA, the initial nickel receptor . This entry also includes Nickel-binding periplasmic protein from Escherichia coli (NikA), which contains a pocket rich in aromatic and arginine residues that lodged a Ni-(H2O)5 2+ species. It has been shown that NikA is able to bind nickel and Fe(III)EDTA in the same pocket
and that His416 is the only direct metal-protein contact .

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .
3,4-dihydroxyphenylacetate 2,3-dioxygenase, Mn/Fe-type (DHPA_dOase_Mn/Fe)
Type: Family

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates. Cleavage of aromatic rings is one of the most important function of dioxygenases. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes cleave the aromatic ring between two hydroxyl groups, whereas extradiol enzymes cleave the aromatic ring between a hydroxylated carbon and another adjacent non-hydroxylated carbon. Extradiol dioxygenases are usually homomultimeric, bind one atom of ferrous ion per subunit and have a subunit size of about 33kDa. It has been shown that the known extradiol dioxygenases are evolutionary related. The conserved glutamate has been shown , in bphC, to be implicated in the binding of the ferrous iron atom.

3,4-dihydroxyphenylacetate 2,3-dioxygenase (HPCD) is an extradiol dioxygenase that catalyzes the oxygen-dependent extradiol cleavage of 3,4-dihydroxyphenylacetate (also known as homoprotocatechuate, HPCA) to produce 5-carboxymethyl-2-hydroxymuconic semialdehyde. Most extradiol dioxygenases contain Fe(II) in their active site, but HPCD can be activated by either Mn(II) or Fe(II). This entry includes HPCDs from both types. The enzyme from Bacillus brevis or Arthrobacter globiformis utilizes Mn(II), whereas the enzyme isolated from Brevibacterium fuscum utilizes Fe(II) .
4-hydroxyphenylacetate 3-monooxygenase, reductase component (HPA_mOase_red)
Type: Family

This entry identifies the reductase component (HpaC) of 4-hydroxyphenylacetate 3-monooxygenase . This enzyme catalyses the first step (hydroxylation at the 3-position) in the degradation of 4-hydroxyphenylacetate to succinate and pyruvate. 4-hydroxyphenylacetate arises from the degradation of tyrosine. These reductases catalyse the reduction of free flavins by NADPH. The flavin is then utilised by the large subunit of the monooxygenase.
4-hydroxyphenylacetate catabolism regulatory protein HpaA (HpaA_TReg)
Type: Family

This putative transcriptional regulator, which contains both the substrate-binding, dimerisation domain and the helix-turn-helix DNA-binding domain of the AraC famil, is located proximal to genes of the 4-hydroxyphenylacetate catabolism pathway .
3,4-dihydroxyphenylacetate 2,3-dioxygenase (HPCD)
Type: Family

3,4-dihydroxyphenylacetate (homoprotocatechuate, hpca) 2,3-dioxygenase (HPCD) catalyses the second step in the degradation of 4-hydroxyphenylacetate to succinate and pyruvate. 4-hydroxyphenylacetate arises from the degradation of tyrosine. The enzyme incorporates both atoms of molecular oxygen into hpca, resulting in aromatic ring-opening to yield alpha-hydroxy-delta-carboxymethyl cis-muconic semialdehyde .

HPCD is a member of the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon.
5-carboxymethyl-2-hydroxymuconate semialdehyde dehydrogenase (DH_HpaE)
Type: Family

This entry represents the dehydrogenase responsible for the conversion of 5-carboxymethyl-2-hydroxymuconate semialdehyde to 5-carboxymethyl-2-hydroxymuconate (a tricarboxylic acid). This is the step in the degradation of 4-hydroxyphenylacetic acid via homoprotocatechuate following the oxidative opening of the aromatic ring .
Extradiol ring-cleavage dioxygenase LigAB, LigA subunit (Xdiol_dOase_LigA)
Type: Domain

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes (

) use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues. Extradiol dioxygenases are usually homo-multimeric, bind one atom of ferrous ion per subunit and have a subunit size of about 33kDa. Extradiol dioxygenases can be divided into three classes. Class I and II enzymes (

) show sequence similarity, with the two-domain class II enzymes having evolved from a class I enzyme through gene duplication. Class III enzymes are different in sequence and structure, but they do share several common active-site characteristics with the class II enzymes, in particular the coordination sphere and the disposition of the putative catalytic base are very similar. Class III enzymes usually have two subunits, designated A (

) and B (

).

LigAB is a protocatechuate 4,5-dioxygenase (

) that belongs to the extradiol class III enzyme family. The LigA subunit of this enzyme is multi-helical, containing a compact array of six short helices .
ATPase, V1 complex, subunit H, C-terminal (ATPase_V1-cplx_hsu_C)
Type: Domain

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents the C-terminal domain of subunit H (also known as Vma13p) found in the V1 complex of V-ATPases. This subunit has a regulatory function, being responsible for activating ATPase activity and coupling ATPase activity to proton flow . The yeast enzyme contains five motifs similar to the HEAT or Armadillo repeats seen in the importins, and can be divided into two distinct domains: a large N-terminal domain consisting of stacked α helices, and a smaller C-terminal α-helical domain with a similar superhelical topology to an armadillo repeat .
MHC class II-associated invariant chain, trimerisation (MHC_II-assoc_invariant_trimer)
Type: Domain

Newly synthesized MHCII proteins associate with a chaperone protein called the invariant chain (Ii) and form a nonameric complex (alpha3beta3Ii3) in the endoplasmic reticulum . Ii plays a critical role in the assembly of the MHC, as well as in MHC II antigen processing by stabilising peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place . In antigen-presenting cells (APCs), loading of MHC II molecules with peptides is regulated by Ii, which blocks MHC II antigen-binding sites in pre-endosomal compartments . Several molecules then act upon MHC II molecules in endosomes to facilitate peptide loading: Ii-degrading proteases, the peptide exchange factor, human leukocyte antigen-DM (HLA-DM), and its modulator, HLA-DO (DO).

Ii first assembles into a trimer and then associates with three class II alpha/beta MHC heterodimers. This entry represents the trimerisation domain of Ii. Its structure has been determined by NMR .
Armadillo-like helical (ARM-like)
Type: Homologous_superfamily

This superfamily represents a domain consisting of a multi-helical fold comprising two curved layers of α-helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis . These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids. This topology has been found with a number of repeats and domains, including the armadillo repeat (found in beta-catenins and importins), the HEAT repeat (found in protein phosphatase 2a and initiation factor eIF4G), the PHAT domain (found in Smaug RNA-binding protein), the leucine-rich repeat variant, the Pumilo repeat, and in the H regulatory subunit of V-type ATPases. The sequence similarity among these different repeats or domains is low, however they exhibit considerable structural similarity. Furthermore, the number of repeats present in the superhelical structure can vary between orthologues, indicating that rapid loss/gain of repeats has occurred frequently in evolution. A common phylogenetic origin has been proposed for the armadillo and HEAT repeats .
Tetratricopeptide-like helical domain superfamily (TPR-like_helical_dom_sf)
Type: Homologous_superfamily

The domain represented in this superfamily consists of a multi-helical fold comprised of two curved layers of α-helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis . These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids. The TPR is likely to be an ancient repeat, since it is found in eukaryotes, bacteria and archaea, whereas the PPR repeat is found predominantly in higher plants. The superhelix formed from these repeats can bind ligands at a number of different regions, and has the ability to acquire multiple functional roles .

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins . It mediates protein-protein interactions and the assembly of multiprotein complexes . The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel α-helices . The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.
ArsR-like helix-turn-helix domain (ArsR-like_HTH)
Type: Domain

This domain is found in the arsenical resistance operon repressor (ArsR) and similar prokaryotic, metal regulated homodimeric repressors. The ArsR subfamily of helix-turn-helix bacterial transcription regulatory proteins (winged helix topology) includes several proteins that appear to dissociate from DNA in the presence of metal ions .
EF-hand domain pair (EF-hand-dom_pair)
Type: Homologous_superfamily

This domain superfamily consists of a duplication of two EF-hand units, where each unit is composed of two helices connected by a twelve-residue calcium-binding loop. The calcium ion in the EF-hand loop is coordinated in a pentagonal bipyramidal configuration. Many calcium-binding proteins contain an EF-hand type calcium-binding domain . These include: calbindin D9K, S100 proteins such as calcyclin, polcalcin phl p 7 (a calcium-binding pollen allergen), osteonectin, parvalbumin, calmodulin family of proteins (troponin C, caltractin, cdc4p, myosin essential chain, calcineurin, recoverin, neurocalcin), plasmodial-specific CaII-binding protein Cbp40, penta-EF-Hand proteins (sorcin, grancalcin, calpain), as well as multidomain proteins such as phosphoinositide-specific phospholipase C, dystrophin, Cb1 and alpha-actinin. The fold consists of four helices and an open array of two hairpins.
PH-like domain superfamily (PH-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents the PH domain and structurally related domains.

Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of signalling proteins, where they serve as simple targeting domains that bind lipids .

PH domains have a partly opened β-barrel topology that is capped by an α-helix. The structure of PH domains is similar to the phosphotyrosine-binding domain (PTB) found in IRS-1 (insulin receptor substrate 1) , Shc adaptor and Numb ; to the Ran-binding domain, found in Nup nuclear pore complex and Ranbp1 ; to the Enabled/VASP homology domain 1 (EVH1 domain), found in Enabled, VASP (vasodilator-stimulated phosphoprotein), Homer and WASP actin regulatory protein ; and to the third domain of FERM, found in moesin, radixin, ezrin, merlin and talin .
Cytidylate kinase domain (Cytidylate_kinase_dom)
Type: Domain

Cytidylate kinase (

) catalyses the phosphorylation of cytidine 5'-monophosphate (dCMP) to cytidine 5'-diphosphate (dCDP) in the presence of ATP or GTP.
Orotidine 5'-phosphate decarboxylase, type 2 (OMPdecase_type-2)
Type: Family

Orotidine 5'-phosphate decarboxylase (OMPdecase) catalyses the last step in the
de novo
biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional protein.

This entry represents orotidine 5'-monophosphate decarboxylase type 2 - a distinct subfamily of the same enzyme represented by

.
Envelope glycoprotein E, central and dimerisation domain, flavivirus (Flavi_Glycoprot_E_cen/dimer)
Type: Domain

Flaviviruses and alphaviruses are arthropod-borne, enveloped RNA viruses that cause infections in vertebrate hosts . These viruses have two envelope glycoproteins (also known as 'spike' glycoproteins), one that undergoes proteolytic cleavage to prime the virus (glycoproteins M and P62 in flaviviruses and alphaviruses, respectively), and the other to mediate receptor binding and fusion (glycoproteins E and E1 in flaviviruses and alphaviruses, respectively). Glycoprotein E/E1 is comprised of three domains: domain I (dimerisation domain) is a β-barrel, domain II (central domain) is an elongated β-stranded and α-helical domain, and domain III (immunoglobulin-like domain) is an IgC-like β-sandwich. This entry represents the intertwined central and dimerisation domains found in flaviviral glycoprotein E .
Thiamine pyrophosphate enzyme, central domain (Thiamin_PyroP_enz_cen_dom)
Type: Domain

A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown that some of these enzymes are structurally related. This entry represents the DHS-like NAD/FAD-binding domain of TPP enzymes, which contains a 2-fold Rossman fold.
Thiamine pyrophosphate enzyme, N-terminal TPP-binding domain (Thiamin_PyroP_enz_TPP-bd_dom)
Type: Domain

A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown that some of these enzymes are structurally related. There are two different functional modules in the thiamin diphosphate-binding fold, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This represents the N-terminal TPP-binding domain that in some members has been described as the Pyr-binding module.
Desulforedoxin (Desulforedoxin)
Type: Family

This group represents desulforedoxin, which is a stand-alone version of the desulfoferrodoxin (

) N-terminal domain. Desulforedoxins are small (approximately 36 amino acids) homodimeric non-haem iron proteins. Each subunit contains a high-spin iron atom tetrahedrally bound to four cysteinyl sulphur atoms . The desulforedoxin domain has a metal centre and fold similar to the rubredoxin metal-binding domain, but their spectroscopic properties differ .

Sulphate-reducing bacteria carry a large variety of redox proteins, which collectively allow the flow of electrons to sulphate . The exact function of desulforedoxin is not yet determined. Neelaredoxin and desulfoferrodoxin (

) have been shown to have superoxide dismutase (SOD;

) and superoxide reductase (SOR;

) activities, but these activities reside in the neelaredoxin domain .