SII-SWORD/CoKE huggingface dataset:
Interleukin-10, additional helical (IL-10_add_hlx)
Type: Homologous_superfamily

Human interleukin-10 (IL-10) is a pleiotropic cytokine that inhibits cell-mediated immune responses, primarily by blocking the synthesis of pro-inflammatory cytokines and by inhibiting the expression of cell surface markers involved in antigen presentation and costimulation. In addition, IL-10 acts to enhance humoral immunity. Viral IL-10 homologues act and bind through cellular IL-10 receptors in order to mimic the immunosuppressive properties of cellular IL-10 . The structures of both cellular and viral IL-10 cytokines involve the formation of an intertwined dimer, consisting of 3-4 helices from one chain, and two helices from the other chain. This entry represents the extra two helices found in IL-10 cytokines.
Uncharacterised conserved protein UCP01524, polysaccharide biosynthesis aminopeptidase-like (UCP015244)
Type: Family

The proteins in this entry are encoded by genes located in polysaccharide biosynthesis gene clusters, and are therefore believed to be involved in polysaccharide biosynthesis. The
ste
gene cluster (for
St
reptomyces
e
ps) is involved in exopolysaccharide EPS 139A biosynthesis in Streptomyces sp. 139 .

Members of this group exhibit distant sequence similarity to aminopeptidases (

, MEROPS peptidase family M28).
Esterase/lipase (Esterase_lipase)
Type: Family

Members of this group are esterases, lipases, and (possibly) other hydrolases of the alpha/beta hydrolase fold. The Bacillus stearothermophilus (Geobacillus stearothermophilus) member, Est, has been characterised as a carboxylesterase (

) involved in the detoxification of xenobiotics , and the Bacillus sp. H-257 member has been characterised as monoacylglycerol lipase (

) .

The alpha/beta hydrolase fold is found in a wide range of enzymes with different catalytic functions . These enzymes operate on different substrates, and may lack detectable sequence similarity. Nevertheless, they share structural similarity (an open twisted β sheet surrounded on both sides by α helices) and the arrangement of three catalytic residues (the "catalytic triad"): a nucleophile (usually Ser), an acid (usually Asp), and histidine . The functional roles of the triad residues are as follows: the sidechain group at the Ser position serves as a nucleophilic centre, the His sidechain acts as a general base and is hydrogen bonded to the carboxylic group of the Asp sidechain. Together, His and Asp form a charge relay system .
NAD kinase 2, mitochondrial (NADK2_mit)
Type: Family

NAD kinase 2 (NADK2) can utilise ATP or inorganic polyphosphate, and is localised in the mitochondria .
Methanogenesis marker 5 protein (Methan_mark_5)
Type: Family

The exact function of this protein is unknown, but likely is linked to methanogenesis or a process closely connected to it .
Uncharacterised conserved protein UCP024484 (UCP024484)
Type: Family

This is a small family of archaeal proteins. Their genes are located in an operon containing two genes of box C/D RNA protein complexes. These proteins adopt α/β structure consisting of two subdomains. The N-terminal subdomain contains a HTH motif whereas the C-terminal subdomain shows a partial structural similarity to several nucleic acid binding proteins such as tRNA intron endonucleases , DNA mismatch repair protein MutS, etc. .
Endopolyphosphatase, Ppn1p-related (EndopolyPtase_N1)
Type: Family

Endopolyphosphatases are enzymes that hydrolyse long inorganic phosphate chains to shorter chains of (predominantly) 60 or 3 phosphate units. The Saccharomyces cerevisiae (Baker's yeast) member, Ppn1p, is an essential vacuolar enzyme . It is a homodimer of chains of about 350 amino acids derived by proteolysis, from the amino end, of the precursor sequence. This region contains the metallophosphoesterase domain, which is found in a large number of proteins with phosphoesterase activity.
NTP pyrophosphohydrolase MazG-related, YpjD (MazG-related_YpjD)
Type: Family

Members of this group are distantly related to MazG-type NTP pyrophosphohydrolase (

). Conserved residues of the MazG domain (at least three of the Glu residues, Asp, Lys and Arg), including those shown to be functionally important , are also conserved here. MazG protein of Thermotoga maritima has been shown to have both nucleoside triphosphate pyrophosphohydrolase and pyrophosphatase activities, while Escherichia coli MazG has only NTP pyrophosphohydrolase activity . Therefore, members of this group are tentatively predicted to be pyrophosphohydrolases.

This family includes the putative pyrophosphatase YpjD from Bacillus subtilis. Although its biological role has not been described in detail, YpjD shows significant sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. However, unlike typical tandem-domain MazG proteins, BsYpjD contains a single MazG-like domain .
Galactose-1-phosphate uridylyltransferase, short form, putative (GalT_short)
Type: Family

This group is related to

, galactose-1-phosphate uridylyltransferases (GalT;

).

is a member of the HIT domain superfamily based on structural fold and has a signature HXHXQ. Members of this group are shorter than

members by ~100 residues, but have considerable sequence similarity, including the signature.
LytTR transmembrane transcriptional regulator, putative (LytTR_TM)
Type: Family

Members of this group combine an N-terminal domain with four transmembrane segments and a C-terminal LytTR DNA-binding domain . Accordingly, these proteins are predicted to be involved in transcriptional regulation and signal transduction, but their exact regulatory role or the mode of signal transduction as well as the type of signal they transmit are unknown .
L-threonine kinase (PduX)
Type: Family

Some bacteria, including Salmonella enterica subsp. enterica serovar Typhimurium, degrade 1,2-propanediol by a pathway that requires coenzyme B12, adenosylcobalamin (AdoCbl). Bacteria that harbour this pathway can use propanediol as a sole carbon and energy source. Proteins required for 1,2-propanediol degradation are encoded by the
pdu
operon . Members of this family belong to the GHMP kinase domain superfamily (and are distantly related to galactokinase, L-homoserine kinase, and mevalonate kinase). Since cobalamin biosynthesis requires L-threonine-3P as a substrate for the CobD aminotransferase, PduX is cobalamin biosynthesis-related, which functions in the propanediol degradation pathway as L-threonine kinase .
Oligosaccharide lyase (Oligosacch_lyase)
Type: Family

The Sphingomonas sp. A1 member of this group has been characterised as oligoalginate lyase .
Phosphoesterase, lmo2642-related (Pesteras_lmo2642)
Type: Family

This small family comprises proteins containing one copy of the metallophosphoesterase domain. They possess motifs characteristic of a variety of enzymatically active phosphoesterases , including acid and alkaline phosphatases, phosphoprotein phosphatases, 5'-nucleotidase, bis(5'-nucleosyl)-tetraphosphatase (symmetrical), sphingomyelin phosphodiesterase, 2',3'-cylic-nucleotide 2'-phosphodiesterase and the 3',5'-nucleotide phosphodiesterase CpdA.
Uncharacterised conserved protein thioesterase (UCP_Testerase)
Type: Family

This group is distantly related (sharing some sequence motifs) both to the integrated thioesterase domains (TEI) found in type I polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs), and to the related stand-alone (non-integrated) type II thioesterase (TEII; see

for a full description). Therefore, members of this group are stand-alone proteins related to both TEI and TEII.

Bradyrhizobium japonicum Bll6574 protein (

) is similar to proteins in this group, but has a LysM domain (

) at the C terminus.
Oxidoreductase molybdopterin-binding subunit, IorB-related (OxRdtase_Mopterin-bd_su_IorB)
Type: Family

Isoquinoline 1-oxidoreductase (IOR,

), a heterodimer containing an alpha subunit (IorA) and a beta subunit (IorB; this group), belongs to a group of prokaryotic molybdenum-containing hydroxylases . The beta subunit is highly homologous to the membrane-bound aldehyde dehydrogenase (pyrroloquinoline-quinone,

) . It contains a strong aldehyde oxidase and xanthine dehydrogenase type of molybdopterin binding domain and a weak a/b hammerhead domain.
Galactokinase, glycosyltransferase (Galk_glycosyltransferase)
Type: Family

Members of this family are predicted to be bifunctional enzymes.
Condensin-2 complex subunit D3 (NCAPD3)
Type: Family

This group contains condensin-2 complex subunit D3. It is a regulatory subunit of the condensin-2 complex (contains the SMC2 and SMC4 heterodimer, and 3 non SMC subunits that probably regulate the complex: NCAPH2, NCAPD3 and NCAPG2), a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis .
Uncharacterised conserved protein UCP014405, metallopeptidase Zn-binding site (UCP014405_Zn-bd)
Type: Family

Members of this family contain a characteristic pattern of the Zn-binding site of neutral zinc metallopeptidases. Members of this family have not been characterised.
Fe(2+)-dicitrate sensor, transmembrane component (Ferrdict_sens_TM)
Type: Family

This family contains transmembrane signal transduction proteins involved in Fe2+ dicitrate sensing. Experimentally characterised members include Escherichia coli FecR and Pseudomonas putida PupR . Members of this family are a distinct group of anti-sigma factors .

In E. coli, binding of ferric citrate to the outer membrane receptor/transporter protein FecA initiates a signal that is transmitted by FecR across the cytoplasmic membrane into the cytoplasm where FecI, the sigma factor, is activated . The periplasmic N terminus of FecA interacts with the periplasmic C-terminal portion of FecR, then FecR transmits the signal across the membrane, and the cytoplasmic N terminus of FecR interacts with FecI, which results in FecI activation .
Co/Fe-chelatase, CbiX-related (CbiX-rel)
Type: Family

This group represents proteins that contain an N-terminal CbiX (class II chelatase) domain, and an additional unique C-terminal domain of unknown function.

This group of proteins is able to chelate both Fe
2+
and Co
2+
and can therefore act in both sirohaem and cobalamin biosynthesis . It functions primarily as a cobaltochelatase that inserts cobalt into sirohydrochlorin during the biosynthesis of cobalamin (vitamin B
12
) . This form of the enzyme contains two copies of the cobalamin biosynthesis CbiX domain (

),while the stand-alone form contains one. A similar protein named SirB (YlnE), encoded within a small sirohaem biosynthetic operon, has been shown to be capable of inserting ferrous iron into sirohydrochlorin during the biosynthesis of sirohaem .

Members of this family belong to the class II chelatases, which are defined as homomeric monofunctional chelatases that do not require ATP for catalysis . Class II chelatases include, in addition to CbiX and SirB, cobaltochelatase CbiK (

) and protoporphyrin ferrochelatase HemH . All of these enzymes share some distant sequence similarity, and CbiK and HemH have a similar overall topology , which is also predicted for CbiX. It has been suggested that class II chelatases may have evolved from a primordial CbiX
S
type of enzyme .
Glutamate synthase large subunit domain 1 stand-alone protein (Glu_synth_lsu_1)
Type: Family

The large (alpha, GltB) subunit of bacterial glutamate synthase (GOGAT, GltS) consists of three domains. This entry represents a stand-alone version of the N-terminal amidotransferase domain that is found in archaeal GOGAT, where the large subunit is represented by three separate proteins corresponding to the three domains of the "standard" bacterial enzyme . Similar organisation of GOGAT with stand-alone domains has been found in some bacteria (e.g., Sinorhizobium meliloti and Thermotoga maritima), but its function is not clear in those organisms where the "standard" (integrated) bacterial form is also present (e.g., Sinorhizobium meliloti).

The amidotransferase domain of the bacterial GOGAT is characterised by a four layer α/β/β/α architecture and contains the typical catalytic centre. The N-terminal Cys-1 catalyses the hydrolysis of L-glutamine generating ammonia and the first molecule of L-glutamate .

Originally, only the ORF encoding the central domain of GOGAT was recognised and annotated as GltB in archaea, and the rest of the large subunit was thought to be missing, which may lead to some misannotations . This led to speculation that the archaeal form of the GOGAT large subunit was the ancestral minimal form of the enzyme. Later analysis showed, however, that in all archaea where the large subunit has been found, its entire sequence is represented by three separate ORFs .

Glutamate synthase is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channeling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation . GOGAT is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor .
LytTR MHYE transcriptional regulator, putative (LytTR_MHYE)
Type: Family

Members of this group combine the LytTR DNA-binding transcriptional regulator domain with an N-terminal membrane-bound MHYE domain that consists of three predicted transmembrane segments with conserved Glu, Asp, His and Tyr residues. The membrane topology of this domain is somewhat similar to that of MHYT domain , suggesting that it, too, might be membrane-bound and metal-binding .

A member of this group is RpfD from the plant pathogen Xanthomonas campestris. Although the
rpfD
gene is located in the
rpf
(regulation of pathogenicity factors) locus of X. campestris, mutants with transposon insertion in the
rpfD
gene did not exhibit any discernible phenotype . The function of this protein is not yet known.
Ethanolamine/propanediol utilisation protein, EutP/PduV (EutP_PduV)
Type: Family

Members of this family function in ethanolamine and propanediol degradation pathways. Both pathways require coenzyme B12 (adenosylcobalamin, AdoCbl). Bacteria that harbour these pathways can use ethanolamine as a source of carbon and nitrogen, or propanediol as a sole carbon and energy source, respectively.

The exact roles of the EutP and PduV proteins in these respective pathways are not yet determined, however, EutP is a putative bidirectional acetate kinase that may drive flux through the ethanolamine degradation pathway under anoxic conditions found when Salmonella typhimurium infects host intestine. It may generate ATP that can be used by other enzymes (EutA and EutT) in the eut pathway. It can use GTP instead of ATP with reduced efficiency . Members of this family contain P-loop consensus motifs in the N-terminal part, and are distantly related to various GTPases and ATPases, including ATPase components of transport systems.

Propanediol degradation is thought to be important for the natural Salmonella populations, since propanediol is produced by the fermentation of the common plant sugars rhamnose and fucose . More than 1% of the Salmonella enterica genome is devoted to the utilisation of propanediol and cobalamin biosynthesis. In vivo expression technology has indicated that propanediol utilisation (
pdu
) genes may be important for growth in host tissues, and competitive index studies with mice have shown that
pdu
mutations confer a virulence defect . The
pdu
operon is contiguous and co-regulated with the cobalamin (B12) biosynthesis
cob
operon, indicating that propanediol catabolism may be the primary reason for de novo B12 synthesis in Salmonella .
Precorrin-2 C(20)-methyltransferase (CobI/CbiL)
Type: Family

This entry represents precorrin-2 C20-methyltransferase CobI/CbiL (

), which introduces a methyl group at C-20 on precorrin-2 to produce precorrin-3A during cobalamin biosynthesis (vitamin B12). This reaction is key to the conversion of a porphyrin-type tetrapyrrole ring to a corrin ring . In some species, this enzyme fuse with precorrin-3B C17-methyltransferase as of a bifunctional protein. This entry does not include these bifunctional proteins.
Uroporphyrin-III C-methyltransferase, plant (Uropor_MeTrfase_pln)
Type: Family

Uroporphyrin-III C-methyltransferase (S-Adenosyl-L-methionine:uroporphyrinogen III methyltransferase, SUMT), an enzyme of the sirohaem and cobalamin biosynthetic pathway, catalyses C methylation of uroporphyrinogen III (

) . It transfers two methyl groups from S-adenosyl-L-methionine to the C-2 and C-7 atoms of uroporphyrinogen III to yield precorrin-2 via the intermediate formation of precorrin-1. SUMT is the first enzyme committed to the biosynthesis of either sirohaem or cobalamin (vitamin B
12
) rather than haem, and precorrin-2 is a common intermediate in the biosynthesis of corrinoids such as vitamin B
12
, sirohaem and coenzyme F
430
.

Members of this family represent a separate, plant-specific group of SUMT (also called UPM). They are characterised by an additional unique N-terminal domain of unknown function, and therefore greater length than the canonical SUMTs. Part of this N-terminal domain resembles a transit peptide for localisation to mitochondria or plastids . The protein produced by in vitro expression is able to enter isolated intact chloroplasts but not mitochondria .
Prephenate dehydrogenase, fungal (Prephenate_DH_fun)
Type: Family

Members of this group catalyse a step in tyrosine biosynthesis in the shikimate pathway, which is present only in bacteria, archaea, fungi, and plants . They belong to the prephenate dehydrogenase (PDH) domain superfamily

.

Many of the PDH enzymes are able to use the alternative intermediates of tyrosine biosynthesis, prephenate or L-arogenate, as substrates, having both prephenate dehydrogenase and arogenate dehydrogenase activities, and are sometimes collectively called cyclohexadienyl dehydrogenases . Prephenate dehydrogenase (PDH) (

,

) catalyses oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate. Arogenate dehydrogenase (

) catalyses oxidative decarboxylation of arogenate into tyrosine. The existence of different combinations for routing prephenate to phenylalanine or tyrosine means that the substrate specificity of a particular enzyme (arogenate or prephenate), as well as its susceptibility to feedback regulation by different metabolites is not easily predictable, and must be experimentally studied in detail .

This group represents fungal PDH enzymes. It is closely related to the plant group (

), but is characterised by the unique C-terminal domain found only in the fungal enzymes. The experimentally characterised yeast enzyme is a NAD-dependent prephenate dehydrogenase .
2',3'-cyclic-nucleotide 3'-phosphodiesterase (Cyclic-nucl_3Pdiesterase)
Type: Family

2',3' Cyclic nucleotide phosphodiesterases (CPDases) are enzymes that catalyse at least two distinct steps in the splicing of tRNA introns in eukaryotes. The active site is characterised by two conserved histidine residues . The enzyme has six cysteine residues, four of which are involved in forming two intra-molecular disulphide bridges. One of these bridges is involved in the catalytic activity of the enzyme as it opens when CPDase is semi-reduced .

Proteins in this entryand belong to

and catalyse the reaction
Nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate.
tRNA ligase Trl1, fungi (Trl1_fun)
Type: Family

Budding yeast Trl1 is a tRNA ligase required for tRNA splicing and for both splicing and translation of HAC1 mRNA in the unfolded protein response . Trl1 has phosphodiesterase, polynucleotide kinase, and ligase activities .
CDK5 and ABL1 enzyme substrate 1/2 (CABLES1/2)
Type: Family

This group represents protein CABLES (CDK5 and ABL1 enzyme substrate), including CABLES1 and CABLES2 . CABLES1 is a cyclin-dependent kinase binding protein, primarily involved in cell cycle regulation . CABLES1 binds to different functional domains of p53 and p73 and modifies their cell death-inducing activities . It may be a tumour suppressor in human ovarian cancer . CABLES2 is involved in both p53-mediated and p53-independent apoptotic pathways .
Cyclin P/U (Cyclin_P/U)
Type: Family

This entry represents a group of plant and fungi cyclins belonging to the P/U family. They interact preferentially with CDKA1 .
Phosphoesterase SP1827 (Pesterase_SP1827)
Type: Family

This entry represents a family of proteobacteria type predicted phosphoesterases .
Serine/threonine protein phosphatase, BSU1 (Ser/Thr_prot_Pase_BSU1)
Type: Family

This entry represents a group of plant serine/threonine protein phosphatases, including Arabidopsis BSU1 and BSU1-like proteins (BSLs) . AtBSU1 is a phosphatase that acts as a positive regulator of brassinosteroid (BR) signalling .

This entry also includes putative serine/threonine-protein phosphatases from
Plasmodium
and green algae.
Very-long-chain 3-ketoacyl-CoA synthase (3-ktacl-CoA_syn)
Type: Family

This group represents 3-ketoacyl-CoA synthases (KCSs) from plants . They are also known as very long-chain fatty acid (VLCFA) condensing enzymes, and they catalyse the first committed step during the fatty acid elongation process, which is the condensation of C2 units to acyl-CoA. Arabidopsis contains 21 KCS members .
Tricorn protease (Tricorn_protease)
Type: Family

This is a group of serine peptidases belong to the MEROPS peptidase family S41. The members of this group contain the tricorn core protease of bacteria and archaea. The tricorn protease is responsible for degrading oligopeptides, probably derived from the proteasome. Its crystal structure has been resolved to 2 A resolution .
Aldehyde dehydrogenase NAD(P)-dependent (Aldehyde_DH_NAD(P))
Type: Family

Aldehydes are produced as intermediates during the metabolism of many different compounds including amino acids, carbohydrates, lipids vitamins and steroids . They are highly reactive compounds whose buildup to excess levels can cause cytotoxic, genotoxic and carcinogenic effects. Aldehyde dehydrogenases oxidise these compounds to their respective carboxylic acids. This is necessary both for the operation of these metabolic pathways, and to prevent the concentration of aldehydes within the cell from reaching toxic levels. Proteins in this entry are NAD(P)-dependent aldehyde dehydrogenases, found in a variety of organisms, including general aldehyde dehydrogensases (

), fatty aldehyde dehydrogenases (

), and coniferyl aldehyde dehydrogenase (

). Structural studies of the Rattus norvegicus protein (

) show that this enzyme is a homodimer where each subunit consists of two α-β-α domains . The mode of NAD binding differs substantially from that commonly associated with the Rossman fold.

Not all enzymes in this family are dehydrogenases. The family also includes beta-apo-4'-carotenal oxygenase from
Neurospora crassa
which is required for the final step in the synthesis of the carotenoid pigment neurosporaxanthin by oxidising beta-apo-4'-carotenal ; and 4,4'-diapolycopene aldehyde oxidase from
Methylomonas
which is required for the biosynthesis of a C30 carotenoid dialdehyde pigment .
IGFBP-related, CNN (IGFBP_CNN)
Type: Family

This entry represents a group of IGFBP (insulin-like growth fac- tor (IGF) binding proteins)-related proteins, which have been annotated as the CNN family . Members of the CCN family are composed of an N-terminal secretory signal peptide followed by four conserved domains with homology to insulin-like growth factor binding protein, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal domain (CT) with heparin-binding motifs and sequence similarity to the C termini of von Willebrand factor and mucin. The CCN family includes CCN1 (CYR61) , CCN2 (CTGF), CCN3 , CCN4 (WISP-1) , CCN5 (WISP-2), and CCN6 (WISP-3).
Pullulan 6-glucanohydrolase (Pullulanase)
Type: Family

This group represents a pullulan 6-glucanohydrolase.
PRIB5 (PRIB5)
Type: Family

This group represents a predicted PRIB5 protein.