SII-SWORD/CoKE huggingface dataset:
Holocytochrome c/c1 synthase (Holocyt_c/c1_synthase)
Type: Family

Holocytochrome c-type synthase (HCCS, also known as cytochrome c-type heme lyase) (

) and holocytochrome-c1 synthase (CC1HL, also known as cytochrome c1 heme lyase) are mitochondrial enzymes that catalyse the covalent attachment of a haem group on two cysteine residues of cytochrome c and c1. These two enzymes are functionally and evolutionary related. There are two conserved regions, the first is located in the central section and the second in the C-terminal section. These enzymes contain a conserved histidine, which is key to interact with the heme iron and to form the HCCS:heme complex, the platform for interaction with apocytochrome c .
Diphtheria toxin (NAD+-dipthamide ADP-ribosyltransferase) (Diphtheria_toxin)
Type: Family

Diphtheria toxin (

) is a 58kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis . The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows:

NAD
+
+ peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide

The crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution . The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the α+β type; a transmembrane (TM) domain, which consists of 9 α-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened β-barrel with a jelly-roll-like topology . The TM- and receptor binding-domains together constitute fragment B.
Glycoside hydrolase, family 39 (Glyco_hydro_39)
Type: Family

Glycoside hydrolase family 39 (

) comprises enzymes with several known activities such as alpha-L-iduronidase (

), beta-xylosidase (

), and alpha-1,4-L-rhamnosidase .

The most highly conserved regions in these enzymes are located in their N-terminal parts. These contain a glutamic acid residue which, on the basis of similarities with other families of glycosyl hydrolases , probably acts as the proton donor in their 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.
ABC transporter type 1, transmembrane domain MetI-like (MetI-like)
Type: Domain

This entry recognises ABC transmembrane domains where the TMD is on a separate protein, such as the D-methionine transport system permease protein MetI. The crystal structure of the high-affinity Escherichia coli MetNI methionine uptake transporter has been solved. Each MetI subunit is organised around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK) ABC transporters, which contain six helices .

ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) . In importers, the TMD displays a distinctive signature, the EAA motif, a 20 amino acid conserved sequence located about 100 residues from the C terminus. The motif is hydrophilic and has been found to reside in a cytoplasmic loop located between the penultimate and the antepenultimate transmembrane segment in all proteins with a known topology . It appears to play an important role in ensuring the correct assembly of the prokaryotic ABC transport complex and constituting an interaction site with the so-called helical domain of the ABC module .
Nickel-dependent hydrogenase b-type cytochrome subunit (Ni-dep_Hydgase_cyt-B)
Type: Family

Bacterial membrane-bound nickel-dependent hydrogenases seem to be associated with a b-type cytochrome involved in electron transfer from hydrogen to oxygen. This cytochrome is a protein of about 28kDa that seems to have four transmembrane regions, which include several histidine residues that may be involved in coordination of the haem iron group. The gene coding for this cytochrome is adjacent to that coding for the large subunit of the hydrogenase. It has been assigned a variety of names in different species: hupC, hyaC, hydC or hoxZ.

Every genome which contains a member of this family posesses a Ni/Fe hydrogenase according to Genome Properties (

), and most are gene clustered with other hydrogenase components. Some Ni/Fe hydrogenase-containing species lack a member of this family but contain other CytB homologues, which may substitute for it.
Metallothionein, family 14, prokaryote (Metalthion_fam14_prok)
Type: Family

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium and nickel. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds . An empirical classification into three classes was proposed by Kojima , with class III MTs including atypical polypeptides composed of gamma-glutamylcysteinyl units. Class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences. The MT superfamily is subdivided into families, subfamilies, subgroups, and isolated isoforms and alleles. The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects , e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range.

Family 14 consists of prokaryota MTs. Its members are recognised by the sequence pattern K-C-A-C-x(2)-C-L-C.The taxonomic range of the members extends to cyanobacteria. Known characteristics are: 53 to 56 AAs; 9 conserved Cys; one conserved tyrosine residue; one conserved histidine residue; contain other unusual residues.
P-type trefoil domain (P_trefoil_dom)
Type: Domain

A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins . It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulphide bonds with connectivity 1-5, 2-4, 3-6. This leads to a characteristic three leafed structure ('trefoil'). The P-type domain is clearly composed of three looplike regions. The central core of the domain consists of a short two-stranded antiparallel β-sheet, which is capped by an irregular loop and forms a central hairpin (loop 3). The β-sheet is preceded by a short α-helix, with majority of the remainder of the domain contained in two loops, which lie on either side of the central hairpin.

This domain has been found in a variety of extracellular eukaryotic proteins , including:

Protein pS2 (TFF1), a protein secreted by the stomach mucosa

Spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion

Intestinal trefoil factor (ITF) (TFF3)

Xenopus laevis stomach proteins xP1 and xP4

Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1 (FIM-C.1), proteins which may be involved in defence against microbial infections by protecting the epithelia from the external environment

Xenopus skin protein xp2 (or APEG)

Zona pellucida sperm-binding protein B (ZP-B)

Intestinal sucrase-isomaltase (

/

), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyses sucrose, maltose and isomaltose

Lysosomal alpha-glucosidase (

)
ABC transporter, permease protein, BtuC-like (ABC_transptr_permease_BtuC)
Type: Family

This entry represents a family of ABC transporter permease proteins. It includes the vitamin B12 import system permease protein BtuC, and the Fe(3+) dicitrate transport system permease proteins FecC and FecD, among many others.

BtuC is a component of the ABC transporter complex BtuCD, which facilitates uptake of vitamin B12 into the cytoplasm of Escherichia coli .

FecC and FecD are components of of the fec operon, a Periplasmic-Binding-Protein (PBP)-dependent transport system for ferric dicitrate in Escherichia coli . FecC and FecD exhibit homology to each other and are localized in the cytoplasmic membrane.
Magnesium chelatase ChlI-like, catalytic domain (Mg_chelatse_chII-like_cat_dom)
Type: Domain

This domain can be found in the magnesium chelatase ChlI subunit, the catalytic domain that binds and hydrolyses ATP. This domain contains the nucleotide binding Walker motif and can also be found in the competence protein ComM from Haemophilus influenzae and Lon proteases from archaea.

Magnesium-chelatase is a three-component enzyme that catalyses the insertion of Mg
2+
into protoporphyrin IX. This is the first unique step in the synthesis of (bacterio)chlorophyll. As a result, it is thought that Mg-chelatase has an important role in channeling intermediates into the (bacterio)chlorophyll branch in response to conditions suitable for photosynthetic growth. ChlI and BchD have molecular weights between 38-42kDa .
Transcription regulator HTH, GntR (Tscrpt_reg_HTH_GntR)
Type: Domain

Many bacterial transcription regulation proteins bind DNA through a helix-turn-helix (HTH) motif, which can be classified into subfamilies on the basis of sequence similarities. The HTH GntR family has many members distributed among diverse bacterial groups that regulate various biological processes. It was named GntR after the Bacillus subtilis repressor of the gluconate operon . Family members include GntR, HutC, KorA, NtaR, FadR, ExuR, FarR, DgoR and PhnF. The crystal structure of the FadR protein has been determined . In general, these proteins contain a DNA-binding HTH domain at the N terminus, and an effector-binding or oligomerisation domain at the C terminus (

). The DNA-binding domain is well conserved in structure for the whole of the GntR family, consisting of a 3-helical bundle core with a small β-sheet (wing); the GntR winged helix structure is similar to that found in several other transcriptional regulator families. The regions outside the DNA-binding domain are more variable and are consequently used to define GntR subfamilies . This entry represents the N-terminal DNA-binding domain of the GntR family.
Initiator Rep protein, WH1 domain (Initiator_Rep_WH1)
Type: Domain

This entry represents the WH1 domain found in the initiator of plasmid replication proteins, RepA and related sequences. RepA is a protein from Escherichia coli involved in plasmid replication. The RepA protein binds to DNA repeats that flank the repA gene . A similar RepA family of proteins with wider distribution are the bacterial plasmid DNA replication initiator proteins (see

).

These proteins consist of two domains containing a winged helix-turn-helix motif. The N-terminal domain, WH1, is involved in the dimerization of RepE and an auxiliary binding to DNA. The C-terminal domain, WH2, is related to a sequence-specific binding to the common 8 bp of the iteron .
Auxin-binding protein (Auxin-bd)
Type: Family

Auxin binding protein is located in the lumen of the endoplasmic reticulum (ER). The primary structure contains an N-terminal hydrophobic leader sequence of 30-40 amino acids, which could represent a signal for translocation of the protein to the ER . The mature protein comprises around 165 residues, and contains a number of potential N-glycosylation sites. In vitro transport studies have demonstrated co-translational glycosylation . Retention within the lumen of the ER correlates with an additional signal located at the C terminus, represented by the sequence Lys-Asp-Glu-Leu, known to be responsible for preventing secretion of proteins from the lumen of the ER in eukaryotic cells .
Flagellar L-ring protein (Flag_Lring)
Type: Family

The flgH, flgI and fliF genes of Salmonella typhimurium encode the major proteins for the L, P and M rings of the flagellar basal body . In fact, the basal body consists of four rings (L,P,S and M) surrounding the flagellar rod, which is believed to transmit motor rotation to the filament . The M ring is integral to the inner membrane of the cell, and may be connected to the rod via the S (supramembrane) ring, which lies just distal to it. The L and P rings reside in the outer membrane and periplasmic space, respectively. FlgH and FlgI, which are exported across the cell membrane to their destinations in the outer membrane and periplasmic space, have typical N-terminal cleaved signal-peptide sequences. FlgH is predicted to have an extensive β-sheet structure, in keeping with other outer membrane proteins .
Plant non-specific lipid-transfer protein/Par allergen (Plant_nsLTP)
Type: Family

Plant cells contain proteins, called non-specific lipid-transfer proteins (nsLTPs) , which transfer phospholipids, glycolipids, fatty acids and sterols from liposomes or microsomes to mitochondria and are thought to be involved in plant defense. These proteins, expressed throughout the plant tissues but predominantly found in edible parts , could play a major role in membrane biogenesis by conveying phospholipids such as waxes or cutin from their site of biosynthesis to membranes unable to form these lipids. LTPs exist in animal and plant tissues, including rat liver cytosol, potato tuber, castor bean, maize seedlings, spinach, barley and wheat. While there is no sequence similarity between animal and plant LTPs, similarity between the plant proteins is high. Plant LTPs are proteins of about 9 Kd (90 amino acids), containing eight conserved cysteine residues forming 4 disulphide bridges which allow to form a stable, compact barrel-like structure, which is essential for lipid binding . Plant TLPs are also similar to alpha-amylase inhibitor I2 from the seeds of Indian finger millet and amylase/protease inhibitors from rice and barley.

Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Par j 1 and Par j 2.
Small ribosomal subunit protein bS6 (Ribosomal_bS6)
Type: Family

The small subunits of bacterial and eukaryotic ribosomes have the same overall shapes (with structural elements described as head, body, platform, beak and shoulder). Ribosomal protein bS6 is one of the proteins from the small ribosomal subunit. . In Escherichia coli, bS6 is known to bind together with bS18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle bS6 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 .
Small ribosomal subunit protein eS12 (Ribosomal_eS12)
Type: Family

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The small ribosomal subunit protein eS12 contains 130-150 amino acid residues, and is thought to be involved in the translation initiation step. This family consists of eukaryotic S12 ribosomal proteins, including those from vertebrates , Trypanosoma brucei , Caenorhabditis elegans, Drosophila and Saccharomyces cerevisiae (Baker's yeast).

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 .
TonB-dependent receptor-like, beta-barrel (Beta-barrel_TonB)
Type: Domain

This entry represents the β-barrel domain which contains the plug domain (

). This β-barrel domain is also found in vitamin B12 transporter BtuB and ferric citrate outer membrane transporter FecA , among others.

TonB proteins are bacterial membrane proteins that play a crucial role in energy-dependent active transport systems. They have an N-terminal plug domain which acts as the channel gate, blocking the pore until the channel is bound by a ligand when it undergoes conformational changes and opens the channel and a C-terminal β-barrel domain. In Escherichia coli, the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space . These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of TonB, these receptors bind their substrates but do not carry out active transport. TonB-dependent regulatory systems consist of six components: a specialised outer membrane-localised TonB-dependent receptor (TonB-dependent transducer) that interacts with its energising TonB-ExbBD protein complex, a cytoplasmic membrane-localised anti-sigma factor and an extracytoplasmic function (ECF)-subfamily sigma factor . The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes. Energy for active transport is again obtained through physical interaction with TonB . The proteins that are currently known or presumed to interact with TonB include BtuB, CirA, FatA, FcuT, FecA , FhuA , FhuE, FepA which is important for iron uptake and allows the bacterium to extract iron from the environment , FptA, HemR, IrgA, IutA, PfeA, PupA and Tbp1. The TonB protein also interacts with some colicins.
Glucagon/GIP/secretin/VIP (Glucagon_GIP_secretin_VIP)
Type: Domain

A number of polypeptidic hormones, mainly expressed in the intestine or the pancreas, belong to a group of structurally related peptides . Once such hormone, glucagon is widely distributed and produced in the alpha-cells of pancreatic islets . It affects glucose metabolism in the liver by inhibiting glycogen synthesis, stimulating glycogenolysis and enchancing gluconeogenesis. It also increases mobilisation of glucose, free fatty acids and ketone bodies, which are metabolites produced in excess in diabetes mellitus. Glucagon is produced, like other peptide hormones, as part of a larger precursor (preproglucagon), which is cleaved to produce glucagon, glucagon-like protein I and glucagon-like protein II . The structure of glucagon itself is fully conserved in all known mammalian species . Other members of the structurally similar group include glicentin precursor, secretin, gastric inhibitory protein, vasoactive intestinal peptide (VIP), prealbumin, peptide HI-27 and growth hormone releasing factor.