SII-SWORD/CoKE huggingface dataset:
Intermediate filament protein, conserved site (IF_conserved)
Type: Conserved_site

Intermediate filaments (IF) are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins, which has been subdivided in six major subgroups:

Type I: Acidic cytokeratins.

Type II: Basic cytokeratins.

Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin.

Type IV: Neurofilaments L, H and M, alpha-internexin and nestin.

Type V: Nuclear lamins A, B1, B2 and C.

Type VI: 'Orphan' IF proteins, which are more distant in terms of their amino acid sequences.

All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled- coiled α-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins.

While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain. The IF rod domain is approximately 310 residues long in all cytoplasmic IF proteins and close to 350 residues in the nuclear ones. The IF rod domain exhibits an interrupted α-helical conformation and reveals a pronounced seven-residue periodicity in the distribution of apolar residues. The heptad periodicity within the rod domain is interrupted in several places, which generates four consecutive α-helical segments: 1A and 1B, which together form the so-called coil 1, and 2A and 2B, which form coil 2. The four α-helical segments are interconnected by relatively short, variable linkers L1, L12 and L2 .

IF proteins have a very strong tendency to dimerize via the formation of an α-helical coiled coil (CC) by their rod domains .

This entry represents a conserved region situated at the very end of the 2B segment, which is critically involved in specific dimer-dimer interactions within the mature filament .
Pectinesterase, Tyr active site (Pectinesterase_Tyr_AS)
Type: Active_site

Pectinesterase

(pectin methylesterase) catalyses the de-esterification of pectin into pectate and methanol. Pectin is one of the main components of the plant cell wall. In plants, pectinesterase plays an important role in cell wall metabolism during fruit ripening. In plant bacterial pathogens such as Erwinia carotovora and in fungal pathogens such as Aspergillus niger, pectinesterase is involved in maceration and soft-rotting of plant tissue. Plant pectinesterases are regulated by pectinesterase inhibitors, which are ineffective against microbial enzymes .

Prokaryotic and eukaryotic pectinesterases share a few regions of sequence similarity. The crystal structure of pectinesterase from Erwinia chrysanthemi revealed a β-helix structure similar to that found in pectinolytic enzymes, though it is different from most structures of esterases . The putative catalytic residues are in a similar location to those of the active site and substrate-binding cleft of pectate lyase.

The entry represents a region found in the N-terminal section of these enzymes; it contains a conserved tyrosine which may play a role in the catalytic mechanism .
Aspartate kinase, conserved site (Aspartate_kinase_CS)
Type: Conserved_site

Aspartate kinase (

) (AK) catalyzes the first reaction in the aspartate pathway; the phosphorylation of aspartate. The product of this reaction can then be used in the biosynthesis of lysine or in the pathway leading to homoserine, which participates in the biosynthesis of threonine, isoleucine and methionine .

In bacteria there are three different aspartate kinase isozymes which differ in sensitivity to repression and inhibition by Lys, Met and Thr. AK1 and AK2 are bifunctional enzymes which both consist of an N-terminal AK domain and a C-terminal homoserine dehydrogenase domain. AK1 is involved in threonine biosynthesis and AK2, in that of methionine. The third isozyme, AK3 is monofunctional and involved in lysine synthesis. In archaea and plants there may be a single isozyme of AK which in plants is multifunctional.

This entry represents a region encoding aspartate kinase activity found in both the monofunctional and bifunctional enzymes.

Synonym(s): Aspartokinase
Sodium:galactoside symporter, conserved site (Na/Gal_symport_CS)
Type: Conserved_site

It has been shown that integral membrane proteins that mediate the intake 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. This collection of sequences represents the sodium: galactoside symporter family (SGF).

Like sugar transport proteins, these integral membrane proteins are predicted to comprise twelve membrane spanning domains.
Peptidase S11, D-alanyl-D-alanine carboxypeptidase A (Peptidase_S11)
Type: Family

This group of serine peptidases belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE). The protein fold of the peptidase domain for members of this family resembles that of D-Ala-D-Ala-carboxypeptidase B, the type example for clan SE.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endo-peptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S27) of serine protease have been identified, these being grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural similarity and other functional evidence. Structures are known for four of the clans (SA, SB, SC and SE): these appear to be totally unrelated, suggesting at least four evolutionary origins of serine peptidases and possibly many more .

Not with standing their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (SA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

Bacterial cell walls are complex structures containing amino acids and amino sugars, with alternating chains of N-acetylglucosamine and N-acetyl-muramic acid units linked by short peptides : the link peptide in Escherichia coli is L-alanyl-D-isoglutamyl-L-meso-diaminopimelyl-D-alanine. The chains are usually cross-linked between the carboxyl of D-alanine and the free amino group of diaminopimelate. During the synthesis of peptidoglycan, the precursor has the described tetramer sequence with an added C-terminal D-alanine .

D-Ala-D-Ala carboxypeptidase A is involved in the metabolism of cell components ; it is synthesised with a leader peptide to target it to the cell membrane . After cleavage of the leader peptide, the enzyme is retained in the membrane by a C-terminal anchor. There are three families of serine-type D-Ala-D-Ala peptidase, which are also known as low molecular weight penicillin-binding proteins.

Family S11 contains only D-Ala-D-Ala peptidases, unlike families S12 and S13, which contain other enzymes, such as class C beta-lactamases and D-amino-peptidases . Although these enzymes are serine proteases, some members of family S11 are partially inhibited by thiol-blocking agents .
Sulphate anion transporter, conserved site (S04_transporter_CS)
Type: Conserved_site

A number of proteins involved in the transport of sulphate across a membrane as well as some yet uncharacterised proteins have been shown to be evolutionary related. These proteins are:

Neurospora crassa sulphate permease II (gene cys-14).

Yeast sulphate permeases (genes SUL1 and SUL2).

Rat sulphate anion transporter 1 (SAT-1).

Mammalian DTDST, a probable sulphate transporter which, in human, is involved in the genetic disease, diastrophic dysplasia (DTD).

Sulphate transporters 1, 2 and 3 from the legume Stylosanthes hamata.

Human pendrin (gene PDS), which is involved in a number of hearing loss genetic diseases.

Human protein DRA (Down-Regulated in Adenoma).

Soybean early nodulin 70.

Escherichia coli hypothetical protein ychM.

Caenorhabditis elegans hypothetical protein F41D9.5.

These proteins are highly hydrophobic and seem to contain about 12 transmembrane domains.
Pili assembly chaperone, conserved site (Pili_assmbl_chaperone_CS)
Type: Conserved_site

Most Gram-negative bacteria possess a supramolecular structure - the pili - on their surface, which mediates attachment to specific receptors. Many interactive subunits are required to assemble pili, but their assembly only takes place after translocation across the cytoplasmic membrane. Periplasmic chaperones assist pili assembly by binding to the subunits, thereby preventing premature aggregation . Pili chaperones are structurally, and possibly evolutionarily, related to the immunoglobulin superfamily : they contain two globular domains, with a topology identical to an immunoglobulin fold .

This entry represents a highly conserved region located in the C-terminal section of the first globular domain.
Ammonium transporter, conserved site (Ammonium_transpt_CS)
Type: Conserved_site

A number of evolutionarily-related proteins have been found to be involved in the transport of ammonium ions across membranes .

Members of this family include:

Saccharomyces cerevisiae ammonium transporters MEP1, MEP2 and MEP3.

Arabidopsis thaliana high affinity ammonium transporter (gene AMT1).

Corynebacterium glutamicum ammonium and methylammonium transport system.

Escherichia coli putative ammonium transporter amtB.

Bacillus subtilis nrgA.

Mycobacterium tuberculosis hypothetical protein MtCY338.09c.

Synechocystis sp. (strain PCC 6803) hypothetical proteins sll0108, sll0537 and sll1017.

Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical proteins MJ0058 and MJ1343.

Caenorhabditis elegans hypothetical proteins C05E11.4, F49E11.3 and M195.3.

As expected by their transport function, these proteins are highly hydrophobic and seem to contain from 10 to 12 transmembrane domains.
CXC chemokine, conserved site (Chemokine_CXC_CS)
Type: Conserved_site

Most members of this family of low-molecular weight proteins seem to have mitogenic, chemotactic or inflammatory activities. They are released by phagocytes, mesenchymal cells and a wide variety of tissue cells, upon exposure to inflammation . These small cytokines are also called intercrines or chemokines. They are cationic proteins of 70 to 100 amino acid residues that share four conserved cysteine residues involved in two disulphide bonds.

The family can be split into two groups, depending on the spacing of two N-terminal Cys residues: in one group (CxC), the cysteines are separated by a single amino acid; in the second (C-C), they are adjacent . The CxC group includes such factors as interleukin-8, platelet factor 4, melanoma growth stimulatory activity protein, macrophage inflammatory protein 2, platelet basic protein, and several others. The 'C-C' group includes the monocyte chemotactic proteins, macrophage inflammatory proteins, amongst others.
Interleukin-7/Interleukin-9, conserved site (IL-7/IL-9_CS)
Type: Conserved_site

Interleukin-7 (IL-7) is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. Interleukin-9 (IL-9) is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T-cells.
Phosphomannose isomerase, type I, conserved site (Pmannose_isomerase-type1_CS)
Type: Conserved_site

Phosphomannose isomerase (PMI) is the enzyme that catalyzes the interconversion of mannose-6-phosphate and fructose-6-phosphate. In eukaryotes, it is involved in the synthesis of GDP-mannose which is a constituent of N- and O-linked glycans as well as GPI anchors. In prokaryotes, it is involved in a variety of pathways including capsular polysaccharide biosynthesis and D-mannose metabolism.
Surfactant-associated polypeptide, palmitoylation site (SP-C_palmitoylation_site)
Type: PTM

This entry represents the palmitoylation site of surfactant associated polypeptide SP-C (also known as Surfactant protein C) and similar mammal proteins.

Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-C, a component of surfactant, is a highly hydrophobic peptide of 35 amino acid residues which is processed from a larger precursor protein. SP-C is post-translationally modified by the covalent attachment of two palmitoyl groups on two adjacent cysteines . The exception is canine SP-C, in which the second Cys is replaced by Phe .
Aldose 1-epimerase, conserved site (Ald1_epimerase_CS)
Type: Conserved_site

Aldose 1-epimerase (

) (mutarotase) is the enzyme responsible for the anomeric interconversion of D-glucose and other aldoses between their alpha- and beta-forms.

The sequence of mutarotase from two bacteria, Acinetobacter calcoaceticus and Streptococcus thermophilus is available . It has also been shown that, on the basis of extensive sequence similarities, a mutarotase domain seems to be present in the C-terminal half of the fungal GAL10 protein which encodes, in the N-terminal part, UDP-glucose 4-epimerase.

The entry represents a conserved site of aldose 1-epimerase, which is centred around a conserved histidine residue and may be involved in the catalytic mechanism.
Glycoside hydrolase, family 32, active site (Glyco_hydro_32_AS)
Type: Active_site

It has been shown that the following glycosyl hydrolases can be classified into a single family on the basis of sequence similarities:

Inulinase (

) (or inulase) from the fungi Kluyveromyces marxianus (Yeast) (Candida kefyr).

Beta-fructofuranosidase (

), commonly known as invertase in fungi and plants and as sucrase in bacteria (gene sacA or scrB).

Raffinose invertase (

) (gene rafD) from Escherichia coli raffinose plasmid pRSD2.

Levanase (

) (gene sacC) from Bacillus subtilis.

One of the conserved regions in these enzymes is located in the N-terminal section and contains an aspartic acid residue which has been shown, in yeast invertase to be important for the catalytic mechanism .
Chromogranin, conserved site (Chromogranin_CS)
Type: Conserved_site

Granins (chromogranins or secretogranins) are a family of acidic proteins present in the secretory granules of a wide variety of endocrine and neuro-endocrine cells. The exact function(s) of these proteins is not yet known but they seem to be the precursors of biologically active peptides and/or they may act as helper proteins in the packaging of peptide hormones and neuropeptides. Apart from their subcellular location and the abundance of acidic residues (Asp and Glu), these proteins do not share many structural similarities. Only one short region, located in the C-terminal section, is conserved in all these proteins, such as:

Chromogranin A (CGA): CGA is a protein of about 420 residues; it is the precursor of the peptide pancreastatin which strongly inhibits glucose- induced insulin release from the pancreas.

Secretogranin 1 (chromogranin B): A sulfated protein of about 600 residues.

Secretogranin 2 (chromogranin C): A sulfated protein of about 650 residues.

Chromogranins and secretogranins together share a C-terminal motif, whereas chromogranins A and B share a region of high similarity in their N-terminal section; this region includes two cysteine residues involved in a disulphide bond.
Kringle, conserved site (Kringle_CS)
Type: Conserved_site

Kringles are autonomous structural domains, found throughout the blood clotting and fibrinolytic proteins. Kringle domains are believed to play a role in binding mediators (e.g., membranes, other proteins or phospholipids), and in the regulation of proteolytic activity . Kringle domains are characterised by a triple loop, 3-disulphide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel β-sheet. They are found in a varying number of copies in some plasma proteins including prothrombin and urokinase-type plasminogen activator, which are serine proteases belonging to MEROPS peptidase family S1A.

This entry represents a conserved site within the kringle domain that contains two of the cysteines involved in disulphide bonds.
Deoxyribonuclease I, active site (Deoxyribonuclease-1_AS)
Type: Active_site

This entry represents the first conserved active site containing a histidine residue .

Deoxyribonuclease I (DNase I) (

) is a vertebrate enzyme which catalyzes the endonucleolytic cleavage of double-stranded DNA to 5'- phosphodinucleotide and 5'-phosphooligonucleotide end-products. DNase I is an enzyme involved in DNA degradation; it is normally secreted outside of the cell but seems to be able to gain access to the nucleus where it is involved in cell death by apoptosis .

As shown in the following schematic representation, DNase I is a glycoprotein of about 260 residues with two conserved disulphide bonds.

+-+ +--------+
| | | |
xxxxxxxxxxxxxxxxx#xxxxxxCxCxxxxx#xxxxxxxxxCxxxxxxxxCxxxxxxxxxxxxx

'C': conserved cysteine involved in a disulphide bond.
'#': active site residue.

DNase I has a pH-optimum around 7.5 and requires calcium and magnesium for full activity. It causes single strand nicks in duplex DNA. A proton acceptor-donor chain composed of a histidine and a glutamic acid produce a nucleophilic hydroxyl ion from water, which cleaves the 3'-P-O bond . DNase I forms a 1:1 complex with G-actin, resulting in the inhibition of DNase activity and loss of the ability of G-actin to polymerise into fibres . DNase I has been used in the treatment of lung problems in patients with cystic fibrosis: here it acts by degrading DNA found in purulent lung secretions, reducing their viscosity and making it easier for the patient to breathe .

The sequence of DNase I is evolutionary related to that of human muscle-specific DNase-like protein and human proteins DHP1 and DHP2. However, the first disulphide bond of DNase I is not conserved in these proteins.
AraC-like, DNA binding HTH domain (HTH_AraC)
Type: Domain

Many bacterial transcription regulation proteins bind DNA through a 'helix-turn-helix' (HTH) motif. One major subfamily of these proteins is related to the arabinose operon regulatory protein AraC [

,

. Except for celD , all of these proteins seem to be positive transcriptional factors.

Although the sequences belonging to this family differ somewhat in length, in nearly every case the HTH motif is situated towards the C-terminal in the third quarter of most of the sequences. The minimal DNA binding domain spans roughly 100 residues and comprises two HTH subdomains: the classical HTH domain and another HTH subdomain with similarity to the classical HTH domain but with an insertion of one residue in the turn-region. The N-terminal and central regions of these proteins are presumed to interact with effector molecules and may be involved in dimerisation .

The known structure of MarA (

) shows that the AraC domain is α-helical and shows the two HTH subdomains both bind the major groove of the DNA. The two HTH subdomains are separated by only 27 angstroms, which causes the cognate DNA to bend.

This entry representsthe full AraC domain containing the two HTH subdomains.
HTH domain AraC-type, conserved site (HTH_AraC-typ_CS)
Type: Conserved_site

Many bacterial transcription regulation proteins bind DNA through a 'helix-turn-helix' (HTH) motif. One major subfamily of these proteins is related to the arabinose operon regulatory protein AraC [

,

. Except for celD , all of these proteins seem to be positive transcriptional factors.

Although the sequences belonging to this family differ somewhat in length, in nearly every case the HTH motif is situated towards the C terminus in the third quarter of most of the sequences. The minimal DNA binding domain spans roughly 100 residues and comprises two HTH subdomains; the classical HTH domain and another HTH subdomain with similarity to the classical HTH domain but with an insertion of one residue in the turn-region. The N-terminal and central regions of these proteins are presumed to interact with effector molecules and may be involved in dimerisation .

The known structure of MarA (

) shows that the AraC domain is α helical and shows the two HTH subdomains both bind the major groove of the DNA. The two HTH subdomains are separated by only 27 angstroms, which causes the cognate DNA to bend.

This entry represents the conserved region covering the first HTH domain and the putative second HTH domain within the AraC binding region.
SAM-dependent methyltransferase RsmI, conserved site (SAM_MeTrfase_RsmI_CS)
Type: Conserved_site

Several uncharacterised proteins have been shown to share regions of similarities, including Escherichia coli hypothetical protein yraL, and HI1654, the corresponding Haemophilus influenzae protein; Bacillus subtilis hypothetical protein yabC; Helicobacter pylori hypothetical protein HP0552; Mycoplasma genitalium and Mycoplasma pneumoniae hypothetical protein MG056; Mycobacterium tuberculosis hypothetical protein MtCI237.19; and Synechocystis sp. (strain PCC 6803) hypothetical protein sll0818.

In bacterial 16S rRNAs, methylated nucleosides are clustered within the decoding centre, and these nucleoside modifications are thought to modulate translational fidelity. The N(4), 2'-O-dimethylcytidine (m(4)Cm) at position 1402 of the Escherichia coli 16S rRNA directly interacts with the P-site codon of the mRNA. RsmI is an AdoMet-dependent methyltransferase responsible for the 2'O-methylation of C1402. It is conserved in almost all species of bacteria .

Proteins of the RsmI family are of about 30 to 34 Kd and contain a number of conserved regions. The signature pattern in this entry is to a highly conserved region in the central section of the proteins.