SII-SWORD/CoKE huggingface dataset:
Fatty acid desaturase type 1, conserved site (FADS-1_CS)
Type: Conserved_site

Fatty acid desaturases are enzymes that catalyse the insertion of a double bond at the delta position of fatty acids. There seem to be two distinct families of fatty acid desaturases which do not seem to be evolutionary related.

Family 1 is composed of:

Stearoyl-CoA desaturase (SCD) (

) .

Family 2 is composed of:

Bacterial fatty acid desaturases.

Plant stearoyl-acyl-carrier-protein desaturase (

) , this enzyme catalyzes the introduction of a double bond at the delta(9) position of steraoyl-ACP to produce oleoyl-ACP. This enzyme is responsible for the conversion of saturated fatty acids to unsaturated fatty acids in the synthesis of vegetable oils.

Cyanobacterial DesA , an enzyme that can introduce a second cis double bond at the delta(12) position of fatty acid bound to membranes glycerolipids. DesA is involved in chilling tolerance; the phase transition temperature of lipids of cellular membranes being dependent on the degree of unsaturation of fatty acids of the membrane lipids.

Members of this entry are endoplasmic reticulum (ER) integral membrane proteins that share the same mushroom-like shape fold consisting of four transmembrane helices (TM1-TM4) which anchor them to the membrane, capped by a cytosolic domain containing a unique 9-10 histidine-coordinating di metal (di-iron) catalytic centre . The structure of mouse stearoyl-CoA desaturase (SDC) revealed that TM2 and TM4 are longer than TM1 and TM3 and protrude into the cytosolic domain, providing three of the nine histidine residues that coordinate the two metal ions, while the other histidine residues are provided by the soluble domain in this enzyme .

This conserved region is found in the C-terminal part of family 1 enzymes; this region is rich in histidine residues and in aromatic residues.
Glycoside hydrolase, family 6, conserved site (Glyco_hydro_6_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 6

comprises enzymes with several known activities; endoglucanase (

); cellobiohydrolase (

). These enzymes were formerly known as cellulase family B.

The 3D structure of the enzymatic core of cellobiohydrolase II (CBHII) from the fungus Trichoderma reesei reveals an α-β protein with a fold similar to the ubiquitous barrel topology first seen in triose phosphate isomerase . The active site of CBHII is located at the C-terminal end of a parallel β barrel, in an enclosed tunnel through which the cellulose threads. Two aspartic acid residues, located in the centre of the tunnel are the probable catalytic residues .
C-5 cytosine methyltransferase (C5_MeTfrase)
Type: Family

C-5 cytosine-specific DNA methylases (

) (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA to produce C5-methylcytosine . In mammalian cells, cytosine-specific methyltransferases methylate certain CpG sequences, which are believed to modulate gene expression and cell differentiation. In bacteria, these enzymes are a component of restriction-modification systems and serve as valuable tools for the manipulation of DNA . The structure of HhaI methyltransferase (M.HhaI) has been resolved to 2.5 A : the molecule folds into 2 domains - a larger catalytic domain containing catalytic and cofactor binding sites, and a smaller DNA recognition domain.

This entry also includes tRNA (cytosine(38)-C(5))-methyltransferase (

), also known as DNMT2 (DNA (cytosine-5)-methyltransferase-like protein 2), that specifically methylates cytosine 38 in the anticodon loop of tRNA (Asp) .
Flavivirus non-structural protein NS4B (Flavi_NS4B)
Type: Domain

Flaviviruses encode a single polyprotein. This is cleaved into three structural and seven non-structural proteins. The NS4B protein is small and poorly conserved among the Flaviviruses. NS4B contains multiple hydrophobic potential membrane spanning regions . NS4B may form membrane components of the viral replication complex and could be involved in membrane localisation of NS3 and NS5 (see

) .
Geminivirus BR1 coat protein (Gemini_BR1)
Type: Family

Geminiviruses are characterised by a genome of circular single-stranded DNA encapsidated in twinned (geminate) quasi-isometric particles, from which the group derives its name . Most geminiviruses can be divided into two subgroups on the basis of host range and/or insect vector: i.e. those that infect dicotyledenous plants and are transmitted by the same whitefly species, and those that infect monocotyledenous plants and are transmitted by different leafhopper vectors. The genomes of the whitefly-transmitted African cassava mosaic virus, Tomato golden mosaic virus (TGMV) and Bean golden mosaic virus (BGMV) possess a bipartite genome. By contrast, only a single DNA component has been identified for the leafhopper-transmitted Maize streak virus (MSV) and Wheat dwarf virus (WDV) . Beet curly top virus (BCTV), and Tobacco yellow dwarf virus belong to a third possible subgroup. Like MSV and WDV, BCTV is transmitted by a specific leafhopper species, yet like the whitefly-transmitted geminiviruses it has a host range confined to dicotyledenous plants.

Sequence comparison of the whitefly-transmitted Squash leaf curl virus (SqLCV) and Tomato yellow leaf curl virus (TYLCV) with the genomic components of TGMV and BGMV reveals a close evolutionary relationship . Amino acid sequence alignments of Potato yellow mosaic virus (PYMV) proteins with those encoded by other geminiviruses show that PYMV is closely related to geminiviruses isolated from the New World, especially in the putative coat protein gene regions . Comparison of MSV DNA-encoded proteins with those of other geminiviruses infecting monocotyledonous plants, including Panicum streak virus and Miscanthus streak virus (MiSV) , reveal high levels of similarity.
Zinc-dependent phospholipase C (Zn_PLipaseC)
Type: Domain

Bacillus cereus contains a monomeric phospholipase C

(PLC) of 245 amino-acid residues that binds three zinc ions . Although PLC prefers to act on phosphatidylcholine, it also shows weak catalytic activity with sphingomyelin and phosphatidylinositol . Sequence studies have shown the PLC protein to be similar to the following:

Alpha toxin from Clostridium perfringens and Clostridium bifermentans, which are zinc-dependent phospholipases C involved in haemolysis and cell rupture .

Lecithinase C from Listeria monocytogenes, which aids cell-to-cell spread by breaking down the 2-membrane vacuoles that surround the bacterium during transfer .

Each of these proteins is a zinc-dependent enzyme, binding 3 zinc ions per molecule . The enzymes catalyse the conversion of phosphatidylcholine and water to 1,2-diacylglycerol and choline phosphate . In B. cereus, there are nine residues known to be involved in binding the zinc ions: 5 His, 2 Asp, 1 Glu and 1 Trp. These residues are all conserved in the Clostridium alpha-toxin .
Pterin 4 alpha carbinolamine dehydratase (Pterin_deHydtase)
Type: Family

Pterin 4 alpha carbinolamine dehydratase is also known as DCoH. DCoH is the dimerisation cofactor of hepatocyte nuclear factor 1 (HNF-1) that functions as both a transcriptional coactivator and a pterin dehydratase . X-ray crystallographic studies have shown that the ligand binds at four sites per tetrameric enzyme, with little apparent conformational change in the protein.
Transthyretin-like (Transthyretin-like)
Type: Family

Transthyretin-related proteins form a nematode-specific expanded protein family that comprises 59 members, 54 of which are predicted to be secreted. The proteins show weak similarity to transthyretin (formerly called prealbumin) which transports thyroid hormones. . Some transthyretin-related genes are induced in response to environmental challenges such as oxidative stress or pathogen exposure. These proteins possess 4 cysteine residues that are conserved within the C. elegans transthyretin-related protein family, which could serve as reactive oxygen sensors or scavengers .

Transthyretin-related protein 52 (TTR-52), a member of this family, is required for efficient cell corpse engulfment by the recognition the surface exposed phosphatidylserine (PS). TTR-52 mediates recognition of apoptotic cells by cross-linking the PS signal with the phagocyte receptor CED-1 .
Arenavirus glycoprotein (Arena_glycoprot)
Type: Family

Arenaviridae are single stranded RNA viruses. The arenaviridae S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein .

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin arenavirus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. It has been established that it is the heterologous glycoprotein that protects against JUNV challenge. A recombinant vaccinia virus that expresses JUNV glycoprotein precursor (VV-GJun) protected seventy-two percent of the animals inoculated with two doses of VV-GJun against the lethal JUNV challenge .
tRNA/rRNA methyltransferase, SpoU type (SpoU_MeTrfase)
Type: Domain

This entry represents a domain found in the spoU protein from E. coli that shows strong similarities to previously characterised 2'-O-methyltransferases . The Mrm1 protein of Saccharomyces cerevisiae has been shown to be required for ribose methylation at a universally conserved nucleotide in the peptidyl transferase centre of the mitochondrial large ribosomal RNA (21S rRNA). Cells reduced in this activity were deficient in formation of functional large subunits of the mitochondrial ribosome. The Mrm1 protein catalyses the site-specific formation of 2'-O-methylguanosine on
in vitro
transcripts of both mitochondrial 21S rRNA and E. coli 23S rRNA providing evidence for an essential modified nucleotide in rRNA .
Mannose-6-phosphate isomerase, type II, C-terminal (Man6P_isomerase-2_C)
Type: Domain

The type II phosphomannose isomerases are bifunctional enzymes

. This entry covers the isomerase region of the protein . The guanosine diphospho-D-mannose pyrophosphorylase region is described in another InterPro entry (see

).

Mannose-6-phosphate isomerase or phosphomannose isomerase (

) (PMI) is the enzyme that catalyses the interconversion of mannose-6-phosphate and fructose-6-phosphate. In eukaryotes PMI is involved in the synthesis of GDP-mannose, a constituent of N-and O-linked glycans and GPI anchors and in prokaryotes it participates in a variety of pathways, including capsular polysaccharide biosynthesis and D-mannose metabolism. PMI's belong to the cupin superfamily whose functions range from isomerase and epimerase activities involved in the modification of cell wall carbohydrates in bacteria and plants, to non-enzymatic storage proteins in plant seeds, and transcription factors linked to congenital baldness in mammals . Three classes of PMI have been defined .
Peptidase U32 (Peptidase_U32)
Type: Family

This is a group of peptidases belonging to MEROPS peptidase family U32 (clan U-). They are classified as collagenases as they are present in bacterial collagenases, involved in bacterial infection. For example, Porphyromonas gingivalis PrtC (Bacteroides gingivalis) , is an enzyme that degrades type I collagen and that seems to require a metal cofactor, or Helicobacter pylori HP0169, another Peptidase U32 protein is required for colonisation of mouse gut.

Novel functions of peptidase U32 proteins have been found, suggesting that these peptidases are involved in diverse cellular processes. The conservation of a CX6CX15CX3/4C motif in several U32 proteases indicates that these proteins bind [Fe-S] clusters. RlhA, a member of the U32 protease family involved in the C-hydroxylation of a cytidine on E. coli 23S rRNA is a Fe-S protein related to iron metabolism . TrhP (tRNA hydroxylation protein P), a member of this family, is involved in prephenate-dependent formation of 5-hydroxyuridine (ho5U) modification at position 34 in tRNAs, the first step in 5-methoxyuridine (mo5U) biosynthesis, which is important for tRNA hydroxylation ensuring the efficient decoding during protein synthesis . UbiU-UbiV are involved in ubiquinone biosynthesis in which the 4Fe-4S clusters bind to each protein have a role in electron transfer chains in hydroxylation reactions .

The peptidases families associated with clan U-have an unknown catalytic mechanism as the protein fold of the active site domain and the active site residues have not been reported.
Defensin, invertebrate/fungal (Defensin_invertebrate/fungal)
Type: Domain

Arthropod defensins are a family of insect and scorpion cysteine-rich antibacterial peptides, primarily active against Gram-positive bacteria . All these peptides range in length from 38 to 51 amino acids. There are six conserved cysteines all involved in intrachain disulphide bonds.

A schematic representation of peptides from the arthropod defensin family is shown below.

+----------------------------+
| |
xxCxxxxxxxxxxxxxxCxxxCxxxxxxxxxCxxxxxCxCxx
| | | |
+---|---------------+ |
+-----------------+

'C': conserved cysteine involved in a disulphide bond.

Although low level sequence similarities have been reported between the arthropod defensins and mammalian defensins, the topological arrangement of the disulphide bonds as well as the tertiary structure are completely different in the two families.
Flagellar motor switch protein FliN-like, C-terminal domain (FliN-like_C)
Type: Domain

This entry represents the C-terminal region of Flagellar motor switch proteins FliN and FliM and similar proteins mainly found in bacteria. This domain seems to play a key role in flagellation .

The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of flagellar rotation and hence controls swimming behaviour. The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour . The switch complex comprises at least three proteins - FliG, FliM and FliN. It has been shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts with FliN . The proteins are not particularly hydrophobic and may be peripheral to the membrane, possibly mounted on the basal body M ring .

Proteins of the surface presentation of antigen (SpoA) group are involved in a secretory pathway responsible for the surface presentation of invasion plasmid antigen needed for the entry of Salmonella and other species into mammalian cells .They could play a role in preserving the translocation competence of the IPA antigens and are required for secretion of the three IPA proteins .
Aminotransferase class IV (Aminotrans_IV)
Type: Family

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies.

This entry represents a subfamily of aminotransferases, called class-IV, with currently consists of proteins of about 270 to 415 amino-acid residues that share a few regions of sequence similarity. Surprisingly, the best conserved region does not include the lysine residue to which the pyridoxal-phosphate group is known to be attached, in ilvE, but is located some 40 residues at the C terminus side of the pyridoxal-phosphate-lysine. The D-amino acid transferases (D-AAT), which are among the members of this entry, are required by bacteria to catalyse the synthesis of D-glutamic acid and D-alanine, which are essential constituents of bacterial cell wall and are the building block for other D-amino acids. Despite the difference in the structure of the substrates, D-AATs and L-ATTs have strong similarity .

Bifunctional aminodeoxychorismate lyase / D-amino acid transaminase from Mycobacterium tuberculosis (also referred to as Rv0812) is a
bifunctional enzyme that catalyses two enzymatic reactions in biochemically unrelated pathways: acts as an aminodeoxychorismate (ADC) lyase (ADCL) in folate biosynthesis, converting 4-amino-4-deoxychorismate (ADC) to 4-aminobenzoate (PABA), and as a D-amino acid transaminase (DAAT) in peptidoglycan (PG) biosynthesis .

This group also includes transaminase htyB from
Aspergillus rugulosus
, which is one of the enzymes required for the biosynthesis of the antifungal agent echinocandin B. HtyB catalyses the production of L-homotyrosine from the intermediate 2-oxo-4-(4-hydroxybenzyl)butanoic acid . Also included in this group is branched-chain amino acid aminotransferase gloG from the yeast
Glarea lozoyensis
, which is required for biosynthesis of the mycotoxin pneumocandin, also a lipohexapeptide of the echinocandin family .
Gonadotropin, beta subunit (Gonadotropin_bsu)
Type: Family

The crystal structures of four growth factors; nerve growth factor, transforming growth factor-beta, platelet-derived growth factor, and human chorionic gonadotropin from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology . These proteins show very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers . Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organisation increases the variety of structures built around this simple structural motif .

Glycoprotein hormones (or gonadotropins) are a family of proteins which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin (TSH) and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. All these hormones consist of two glycosylated chains (alpha and beta). In mammalian gonadotropins, the alpha chain is identical in the four types of hormones but the beta chains, while homologous, are different.

The beta chains are proteins of about 100 to 140 amino acid residues which contain the cysteine-knot domain , as shown in the following schematic representation.

+----------------------+
| +------------|-----------------------------+
| +-|------------|--------+ |
| | | | | |
xxxCxxxxxxxCxCxxCxCxxxxxxxCxxxxxxxxCxxxxxxxCxCxCxxCxxxxxCxxxxxxxxxxx
| | | | | |
| | | | +--+
+-|------------------------+ |
+--------------------------+

'C': conserved cysteine involved in a disulphide bond.
Glycoside hydrolase, family 5 (Glyco_hydro_5)
Type: Domain

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.

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.
Peptidase M2, peptidyl-dipeptidase A (Peptidase_M2)
Type: Family

This group of metallopeptidases belong to the MEROPS peptidase family M2 (clan MA(E)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA. The catalytic residues and zinc ligands have been identified, the zinc ion being ligated to two His residues within the motif HEXXH, showing that the enzyme belongs to the glu-zincin sub-group of metalloproteases .

Peptidyl-dipeptidase A (angiotensin-converting enzyme or ACE,

) is a mammalian enzyme responsible for cleavage of dipeptides from the C-termini of proteins, notably converting decapeptide angiotensin I to the octapeptide angiotensin II . The enzyme exists in two differentially transcribed forms, the most common of which is from lung endothelium; this contains two homologous domains that have arisen by gene duplication . The testis-specific form contains only the C-terminal domain, arising from a duplicated promoter region present in intron 12 of the gene . Both enzymatic forms are membrane proteins that are anchored by means of a C-terminal transmembrane domain. Both domains of the endothelial enzyme are active, but have differing kinetic constants . ACE is well-known as a key part of the renin-angiotensin system that regulates blood pressure and ACE inhibitors are important for the treatment of hypertension .

An ACE homologue, ACE2 (MEROPS identifier M02.006), has been identified in humans that differs from ACE; it preferentially removes carboxy-terminal hydrophobic or basic amino acids and appears to be important in cardiac function .
Transcription antiterminator, conserved site (Transcrpt_antitermin_CS)
Type: Conserved_site

This is a family of bacterial proteins related to the Escherichia coli BglG protein. E. coli BglG protein mediates the positive regulation of the beta-glucoside (bgl) operon by functioning as a transcriptional antiterminator . BglG is an RNA-binding protein that recognises a specific sequence located just upstream of two termination sites within the operon. The activity of bglG is suppressed by its phosphorylation by bglF (EII-bgl), the permease from the beta-glucoside PTS system. BglG is highly similar to other proteins, which also probably act as transcriptional antiterminators.