SII-SWORD/CoKE huggingface dataset:
Glycoside hydrolase, family 5, conserved site (Glyco_hydro_5_CS)
Type: Conserved_site

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 5

comprises enzymes with several known activities; endoglucanase (

); beta-mannanase (

); exo-1,3-glucanase (

); endo-1,6-glucanase (

); xylanase (

); endoglycoceramidase (

).

The microbial degradation of cellulose and xylans requires several types of enzymes. Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family A or as the glycosyl hydrolases family 5 . One of the conserved regions in this family contains a conserved glutamic acid residue which is potentially involved in the catalytic mechanism.
Chalcone/stilbene synthase, active site (Chalcone/stilbene_synthase_AS)
Type: Active_site

Chalcone synthases (CHS) (

) and stilbene synthases (STS) (formerly known as resveratrol synthases) are related plant enzymes, members of the plant polyketide synthase superfamily. CHS is an important enzyme in flavonoid biosynthesis and STS is a key enzyme in stilbene-type phyloalexin biosynthesis. Both enzymes catalyse the addition of three molecules of malonyl-CoA to a starter CoA ester (a typical example is 4-coumaroyl-CoA), producing either a chalcone (with CHS) or stilbene (with STS) .

These enzymes have a conserved cysteine residue, located in the central section of the protein sequence, which is essential for the catalytic activity of both enzymes and probably represents the binding site for the 4-coumaryl-CoA group .
Orotidine 5'-phosphate decarboxylase, active site (OMPdecase_AS)
Type: Active_site

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.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centred around a lysine residue which is essential for the catalytic function of the enzyme.
Pyrimidine-nucleoside phosphorylase, bacterial/eukaryotic (Pyrmidine_PPas_bac/euk)
Type: Family

Two highly similar activities are represented in this group: thymidine phosphorylase (TP, gene deoA,

) and pyrimidine-nucleoside phosphorylase (PyNP, gene pdp,

). Both are dimeric enzymes that function in the salvage pathway to catalyse the reversible phosphorolysis of pyrimidine nucleosides to the free base and sugar moieties. In the case of thymidine phosphorylase, thymidine (and to a lesser extent, 2'-deoxyuridine) is lysed to produce thymine (or uracil) and 2'-deoxyribose-1-phosphate. Pyrimidine-nucleoside phosphorylase performs the analogous reaction on thymidine (to produce the same products) and uridine (to produce uracil and ribose-1-phosphate). PyNP is typically the only pyrimidine nucleoside phosphorylase encoded by Gram-positive bacteria, while eukaryotes and proteobacteria encode two: TP, and the unrelated uridine phosphorylase. In humans, TP was originally characterised as platelet-derived endothelial cell growth factor and gliostatin . Structurally, the enzymes are homodimers, each composed of a rigid all α-helix lobe and a mixed α-helix/β-sheet lobe, which are connected by a flexible hinge . Prior to substrate binding, the lobes are separated by a large cleft. A functional active site and subsequent catalysis occurs upon closing of the cleft. The active site, composed of a phosphate binding site and a (deoxy)ribonucleotide binding site within the cleft region, is highly conserved between the two enzymes of this group. Active site residues (Escherichia coli DeoA numbering) include the phosphate binding Lys84 and Ser86 (close to a glycine-rich loop), Ser113, and Thr123, and the pyrimidine nucleoside-binding Arg171, Ser186, and Lys190. Sequence comparison between the active site residues for both enzymes reveals only one difference , which has been proposed to partially mediate substrate specificity. In TP, position 111 is a methionine, while the analogous position in PyNP is lysine. It should be noted that the uncharacterised archaeal members of this family differ in a number of respects from either of the characterised activities. The residue at position 108 is lysine, indicating the activity might be PyNP-like (though the determinants of substrate specificity have not been fully elucidated). Position 171 is glutamate (negative charge side chain) rather than arginine (positive charge side chain). In addition, a large loop that may "lock in" the substrates within the active site is much smaller than in the characterised members. It is not clear what effect these and other differences have on activity and specificity.
Phosphoenolpyruvate carboxykinase, GTP-utilising, conserved site (PEP_carboxykin_GTP_CS)
Type: Conserved_site

This entry represents a conserved site found in GTP-utilising phosphoenolpyruvate carboxykinase enzymes. An essential cysteine residue has been proposed to be implicated in the catalytic mechanism; this residue is located in the central part of PEPCK and is in the centre of a perfectly conserved region.
BCCT transporter, conserved site (BCCT_CS)
Type: Conserved_site

These prokaryotic transport proteins belong to a family known as BCCT (for Betaine / Carnitine / Choline Transporters) and are specific for compounds containing a quaternary nitrogen atom. The BCCT proteins contain 12 transmembrane regions and are energized by proton symport. They contain a conserved region with four tryptophans in their central region .

This entry represents a conserved sequence region from these proteins containing four tryptophan residues.
Thymidylate kinase (Thymidylate_kinase)
Type: Family

Thymidylate kinase (

; dTMP kinase) catalyses the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:

ATP + thymidine 5'-phosphate = ADP + thymidine 5'-diphosphate

Thymidylate kinase is an ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. The function of dTMP kinase in eukaryotes comes from the study of a cell cycle mutant, cdc8, in Saccharomyces cerevisiae. Structural and functional analyses suggest that the cDNA codes for authentic human dTMP kinase. The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages .
Thymidylate kinase, conserved site (Thymidylate_kin_CS)
Type: Conserved_site

Thymidylate kinase (

; dTMP kinase) catalyses the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:

ATP + thymidine 5'-phosphate = ADP + thymidine 5'-diphosphate

Thymidylate kinase is an ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. The function of dTMP kinase in eukaryotes comes from the study of a cell cycle mutant, cdc8, in Saccharomyces cerevisiae. Structural and functional analyses suggest that the cDNA codes for authentic human dTMP kinase. The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages .
Interleukin-4/interleukin-13, conserved site (IL-4/IL-13_CS)
Type: Conserved_site

Interleukin-4 (IL-4) is a cytokine that plays a central role in the control and regulation of the immune and inflammatory system. IL-4 is a participant in several B-cell activation processes. It also stimulates other cell types such as T cells or mast cells. IL-4 is a glycoprotein of 110 to 131 residues. It contains three disulphide bonds. The position of these disulphide bonds is not highly conserved since the topology of two of them differs in Human and mouse IL-4 .

Interleukin-13 (IL-13) is a recently discovered pleiotropic cytokine, which may be important in the regulation of the inflammatory and immune responses. IL-13 is a glycoprotein of 110 residues.
EGF-like calcium-binding, conserved site (EGF_Ca-bd_CS)
Type: Conserved_site

A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown to be present in a large number of membrane-bound and extracellular, mostly animal, proteins. Many of these proteins require calcium for their biological function, and a calcium-binding site has been found at the N-terminal of some EGF-like domains . Calcium-binding may be crucial for numerous protein-protein interactions.

A common feature of all EGF-like domains is that they are found in the extracellular domain of membrane-bound proteins or in proteins known to be
secreted (exception: prostaglandin G/H synthase). The EGF-like domain includes six cysteine residues which have been shown to be involved in disulfide bonds. The structure of several EGF-like domains has been solved. The fold consists of two-stranded β-sheet followed by a loop to a C-terminal short
two-stranded sheet.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes .

+------------------+ +---------+
| | | |
nxnnC-x(3,14)-C-x(3,7)-CxxbxxxxaxC-x(1,6)-C-x(8,13)-Cx
| |
+------------------+

'n': negatively charged or polar residue [DEQN]
'b': possibly beta-hydroxylated residue [DN]
'a': aromatic amino acid
'C': cysteine, involved in disulphide bond
'x': any amino acid.
Small ribosomal subunit protein eS24 conserved site (Ribosomal_eS24_CS)
Type: Conserved_site

This conserved site is found in eS24 ribosomal proteins from eukaryotes and archaebacteria.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Purine phosphorylase, family 2, conserved site (Purine_phosphorylase-2_CS)
Type: Conserved_site

This entry consists of purine nucleoside phosphorylase (

) (PNP) that catalyses the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules , 6-oxopurine nucleoside phosphorylase (

) that is a purine nucleoside phosphorylase specific for 6-oxopurine nucleosides , 5'-methylthioadenosine phosphorylase (

) (MTAP) that catalyses the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate and xanthosine phosphorylase (

) that degrades all purine nucleosides except adenosine and deoxyadenosine .
Translation elongation factor Ts, conserved site (Transl_elong_Ts_CS)
Type: Conserved_site

This entry represents EF-Tu (EF1A) proteins found primarily in bacteria, mitochondria and chloroplasts.
Small ribosomal subunit protein uS11, conserved site (Ribosomal_uS11_CS)
Type: Conserved_site

Ribosomal protein uS11 plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit. On the basis of sequence similarities, uS11 belongs to a family of bacterial, archaeal and eukaryotic ribosomal proteins. This entry represents a small conserved site found in uS11 ribosomal proteins.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Translationally controlled tumour protein, conserved site (Translation_control_tumour_CS)
Type: Conserved_site

The translationally controlled tumor proteins (TCTPs, such as p21, p23 and histamine releasing factor (HRF)) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in a variety of cellular functions, including microtubule stabilization, cell cycle, apoptosis, and cytokine release. TCTP is ubiquitously expressed in all eukaryotic organisms from protozoa such as Plasmodium sp. to plants and mammals .

This entry represents two conserved sites in these proteins.
Translation initiation factor 1A (eIF-1A), conserved site (TIF_eIF-1A_CS)
Type: Conserved_site

Eukaryotic translation initiation factor A (eIF-1A) (formerly known as eiF-4C) is a protein that seems to be required for maximal rate of protein biosynthesis. It enhances ribosome dissociation into subunits and stabilises the binding of the initiator Met-tRNA to 40S ribosomal subunits . The archaea possess an eIF-1A homologue.
Translationally controlled tumour protein (Translational_control_tumour_p)
Type: Family

Mammalian translationally controlled tumour protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesised in cells during the early growth phase of some types of tumour , but which is also expressed in normal cells. The physiological function of TCTP is still not known. It was first identified as a histamine-releasing factor, acting in IgE +-dependent allergic reactions. In addition, TCTP has been shown to bind to tubulin in the cytoskeleton, has a high affinity for calcium, is the binding target for the antimalarial compound artemisinin, and is induced in vitamin D-dependent apoptosis. TCTP production is thought to be controlled at the translational as well as the transcriptional level .
CAP, conserved site, N-terminal (CAP_CS_N)
Type: Conserved_site

This entry represents the N-terminal conserved site of the CAP protein. Structurally, CAP is a protein of 474 to 551 residues, which consist of two domains separated by a proline-rich hinge. In budding and fission yeasts the CAP protein is a bifunctional protein whose N-terminal domain binds to adenylyl cyclase, thereby enabling that enzyme to be activated by upstream regulatory signals, such as Ras. The N terminus also catalyses cofilin-mediated severing of actin filaments . The C-terminal domain plays a role in recycling cofilin-bound, ADP-actin monomers .

CAP is conserved in higher eukaryotic organisms. Although the role in Ras signalling does not extend beyond yeasts, the actin regulation function is conserved in all eukaryotes .
Sodium:dicarboxylate symporter, conserved site (Na-dicarboxylate_symporter_CS)
Type: Conserved_site

It has been shown that integral membrane proteins that mediate the uptake of a wide variety of molecules with the concomitant uptake of sodium ions (sodium symporters) can be grouped, on the basis of sequence and functional similarities into a number of distinct families. One of these families is known as the sodium:dicarboxylate symporter family (SDF) .

Such re-uptake of neurotransmitters from the synapses, is thought to be an important mechanism for terminating their action, by removing these chemicals from the synaptic cleft, and transporting them into presynaptic nerve terminals, and surrounding neuroglia. This removal is also believed to prevent them accumulating to the point of reaching neurotoxic .

The structure of these transporter proteins has been variously reported to contain from 8 to 10 transmembrane (TM) regions, although 10 now seems to be the accepted value.

Members of the family include: several mammalian excitatory amino acid transporters, and a number of bacterial transporters. They vary with regards to their dependence on transport of sodium, and other ions.
Mitochondrial carrier protein, transmembrane region (MCP_transmembrane)
Type: Repeat

This entry represents the transmembrane region in mitochondrial carrier proteins.

A variety of substrate carrier proteins involved in energy transfer are found in the inner mitochondrial membrane or are integral to the membranes of other eukaryotic organelles such as the peroxisome . Such proteins include:

ADP/ATP carrier protein (ADP/ATP translocase)

2-oxoglutarate/malate carrier protein

Phosphate carrier protein

Tricarboxylate transport protein (or citrate transport protein)

Graves disease carrier protein

Yeast mitochondrial proteins MRS3 and MRS4

Yeast mitochondrial FAD carrier protein

And many others

These mitochondrial carrier proteins share a tripartite structure, consisting of up to three tandem repeats of a domain approximately 100 residues in length . Each domain contains two transmembrane (TM) regions, resulting in a total of six TM domains. Sequence analysis has shown that the TM regions and their adjacent hydrophilic loops are more highly conserved than other parts of the protein, with five of the six TM domains followed by the conserved motif (D/E)-Hy(K/R), where Hy denotes a hydrophobic residue . Structurally, these domains contain six α-helices that form a compact transmembrane unit. This structure exhibits a deep depression on the side facing the space between the inner and outer mitochondrial membranes, resembling a channel-like conformation . It is suggested that substrates bind at the bottom of this cavity, and translocation occurs through a conformational change from a 'pit' to a 'channel' structure.
Folylpolyglutamate synthetase, conserved site (Folylpolyglutamate_synth_CS)
Type: Conserved_site

Folylpolyglutamate synthase

(FPGS) is an ATP-dependent enzyme that is responsible for the addition of a polyglutamate tail to folate and folate derivatives . It plays a key role in the retention of the intracellular folate pool. In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (FPGS activity) are catalyzed by the same enzyme, FolC .

The crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals FPGS to be a modular protein, consisting of two domains, one with a typical mononucleotide-binding fold and the other similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined ω-loop, which contributes both to the active site and to interdomain interactions .

This entry represents a conserved site found in the FPGS enzymes.
Mandelate racemase/muconate lactonizing enzyme, conserved site (Mandel_Rmase/mucon_lact_enz_CS)
Type: Conserved_site

Mandelate racemase

(MR) and muconate lactonizing enzyme

(MLE) are two bacterial enzymes involved in aromatic acid catabolism. They catalyse mechanistically distinct reactions, yet they are related at the level of their primary, quaternary (homooctamer) and tertiary structures . A number of other proteins also seem to be evolutionary related to these two enzymes. These include various plasmid-encoded chloromuconate cycloisomerases

, Escherichia coli protein rspA , E. coli bifunctional DGOA protein, E. coli hypothetical proteins ycjG, yfaW and yidU, and a hypothetical protein from Streptomyces ambofaciens .