SII-SWORD/CoKE huggingface dataset:
SLC26A/SulP transporter (SLC26A/SulP_fam)
Type: Family

The SLC26A/SulP family is a large and ubiquitous family with members derived from archaea, bacteria, fungi, plants and animals. Many organisms including Bacillus subtilis, Synechocystis sp, Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans possess multiple SulP family paralogues. Many of these proteins are functionally characterised, and most are inorganic anion uptake transporters or anion:anion exchange transporters. Some transport their substrate(s) with high affinities, while others transport it or them with relatively low affinities .

SLC26A/SulP family proteins consist of N-and C-termini flanking a transmembrane domain thought to span the lipid bilayer 10-14 times. In most cases, the C-terminal cytoplasmic region includes a STAS (sulfate transporter and anti-sigma factor antagonist) domain .

Malfunctions in members of the SLC26A family of anion transporters are involved in three human diseases: diastrophic dysplasia/achondrogenesis type 1B (DTDST), Pendred's syndrome (PDS) and congenital chloride diarrhoea (CLD). These proteins contain 12 transmembrane helices followed by a cytoplasmic STAS domain at the C terminus. The importance of the STAS domain in these transporters is illustrated by the fact that a number of mutations in PDS and DTDST map to it .

Proteins in this family include:

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

Yeast sulphate permeases (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.
Spike glycoprotein fusion domain, Rhabdovirus (Rhabdo_glycop_FD)
Type: Domain

This entry represents the elongated fusion domain FD (also known as domain IV).

The glycoprotein G from rhabdoviruses, such as rabies virus (RABV), Mokola virus (MOKV) and European bat lyssavirus 1 (EBLV) attaches the virus to host cellular receptor, and induces endocytosis of the virion. It forms the glycoprotein spike which is made up of a trimer of G proteins. Each protomer of the trimer is composed of three domains: a membrane-distal pleckstrin homology domain (PH), a membrane-proximal fusion domain (FD) and a laterally positioned central domain (CD) .

Different families of ssRNA negative-strand viruses contain glycoproteins responsible for forming spikes on the surface of the virion. The glycoprotein spike is made up of a trimer of glycoproteins. These proteins are frequently abbreviated to G protein. Channel formed by glycoprotein spike is thought to function in a similar manner to Influenza virus M2 protein channel, thus allowing a signal to pass across the viral membrane to signal for viral uncoating .
Paxillin, Lim domain 4 (Paxillin_Lim_dom4)
Type: Domain

Paxillin is a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion) . Extensive tyrosine phosphorylation occurs during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens that operate through the 7TM family of G-protein-coupled receptors . Paxillin binds in vitro to the focal adhesion protein vinculin, as well as to the SH3 domain of c-Src, and, when tyrosine phosphorylated, to the SH2 domain of v-Crk . An N-terminal region has been identified that supports the binding of both vinculin and the focal adhesion tyrosine kinase, pp125Fak .

Paxillin is a 68kDa protein containing multiple domains, including four tandem C-terminal LIM domains (each of which binds 2 zinc ions); an N-terminal proline-rich domain, which contains a consensus SH3 binding site; and three potential Crk-SH2 binding sites . The predicted structure of paxillin suggests that it is a unique cytoskeletal protein capable of interaction with a variety of intracellular signalling and structural molecules important in growth control and the regulation of cytoskeletal organisation .

This entry represents the C-terminal fourth Lim domain of Paxillin, which function as an adaptor or scaffold to support the assembly of multimeric protein. This domain shows two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms .
Ammonium transporter (Ammonium_transpt)
Type: Family

All functionally characterised members of the ammonium transporter family are ammonia or ammonium uptake transporters. Some, but not others, also transport methylammonium. Uptake of ammonium/ammonia by AtmB protein from E. coli is electrogenic. Following sequestration of NH4+ at the periplasmic face, NH4+ is deprotonated and neutral NH3 is transported into the cytoplasm. Neutral NH3 and charged H+ are carried separately across the membrane on a unique two-lane pathway, before recombining to NH4+ inside the cell. It also acts as a sensor of the extracellular ammonium concentration .

This entry represents ammonium transporters belonging to the Amt family, but it does not include the Rhesus (Rh) subgroup.
Terpene synthase, N-terminal domain (Terpene_synth_N)
Type: Domain

Sequences containing this domain belong to the terpene synthase family . It has been suggested that this gene family be designated tps (for terpene synthase). Sequence comparisons reveal similarities between the monoterpene (C
10
) synthases, sesquiterpene (C
15
) synthases and the diterpene (C
20
) synthases. It has been split into six subgroups on the basis of phylogeny, called Tpsa-Tpsf .

Tpsa includes vetispiridiene synthase

, 5-epi- aristolochene synthase,

and (+)-delta-cadinene synthase

.

Tpsb includes (-)-limonene synthase,

.

Tpsc includes copalyl diphosphate synthase (kaurene synthase A),

.

Tpsd includes taxadiene synthase,

, pinene synthase,

and myrcene synthase,

.

Tpse includes ent-kaurene synthase B

.

Tpsf includes linalool synthase

.

In the fungus Phaeosphaeria sp. (strain L487) the synthesis of ent-kaurene from geranylgeranyl diphosphate is promoted by a single bifunctional protein .
ATP-dependent Clp protease proteolytic subunit (ClpP)
Type: Family

Clp is an ATP-dependent protease that cleaves a number of proteins, such as casein and albumin and is a member of peptidase family S14. It exists as a heterodimer of ATP-binding regulatory A and catalytic P subunits, both of which are required for effective levels of protease activity in the presence of ATP , although the P subunit alone does possess some catalytic activity . This entry represents the P subunit.

Proteases highly similar to ClpP have been found to be encoded in the genome of bacteria, metazoa, some viruses and in the chloroplast of plants, but seems to be absent in archaea, mollicutes and some fungi .
Krueppel-associated box (KRAB)
Type: Domain

The Krueppel-associated box (KRAB) is a domain of around 75 amino acids that is found in the N-terminal part of about one third of eukaryotic Krueppel-type C2H2 zinc finger proteins (ZFPs) . It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic α-helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box .

The functions currently known for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II and III promoters, binding and splicing of RNA, and control of nucleolus function. The KRAB domain functions as a transcriptional repressor when tethered to the template DNA by a DNA-binding domain. A sequence of 45 amino acids in the KRAB A subdomain has been shown to be necessary and sufficient for transcriptional repression. The B box does not repress by itself but does potentiate the repression exerted by the KRAB A subdomain . Gene silencing requires the binding of the KRAB domain to the RING-B box-coiled coil (RBCC) domain of the KAP-1/TIF1-beta corepressor. As KAP-1 binds to the heterochromatin proteins HP1, it has been proposed that the KRAB-ZFP-bound target gene could be silenced following recruitment to heterochromatin .

KRAB-ZFPs probably constitute the single largest class of transcription factors within the human genome . The KRAB domain is generally encoded by two exons. The regions coded by the two exons are known as KRAB-A and KRAB-B. Although the function of KRAB-ZFPs is largely unknown, they appear to play important roles during cell differentiation and development. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta, KRAB-A interacting protein and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation .
Inosine/uridine-preferring nucleoside hydrolase domain (Inosine/uridine_hydrolase_dom)
Type: Domain

Inosine-uridine preferring nucleoside hydrolase (

) (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan that catalyses the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. This enzyme is important for these parasitic organisms, which are deficient in
de novo
synthesis of purines, to salvage the host purine nucleosides. IUNH from Crithidia fasciculata has been sequenced and characterised, it is an homotetrameric enzyme of subunits of 34 Kd. An histidine has been shown to be important for the catalytic mechanism, it acts as a proton donor to activate the hypoxanthine leaving group.

A highly conserved region located in the N-terminal extremity contains four conserved aspartates that have been shown to be located in the active site cavity.

IUNH is evolutionary related to a number of uncharacterised proteins from various biological sources.

This entry represents the structural domain of IUNH.
Small ribosomal subunit protein uS4, N-terminal (Ribosomal_uS4_N)
Type: Domain

This entry represents the domain found at the N terminus of the small ribosomal subunit uS4.

Small ribosomal subunit protein uS4 was previously known as Ribosomal protein S4 in bacteria and plants and S9 in fungi and animals. S4 is known to bind directly to 16S ribosomal RNA. The crystal structure of a bacterial S4 protein revealed a two domain molecule. The first domain is composed of four helices in the known structure. The second domain is an insertion within domain 1 and displays some structural homology with the ETS DNA binding domain .

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 .
Equine arteritis virus GP2b envelope glycoprotein (Equi_arteri_GP2b)
Type: Family

Equine arteritis virus (EAV) is an enveloped, positive-strand RNA virus belonging to the family Arteriviridae. EAV virions contain six different envelope proteins. GP5 (previously named GL) and the unglycosylated membrane protein M are the major envelope proteins, while the glycoproteins GP2b (previously named Gs), GP3, and GP4 are minor structural proteins . GP2b is a class I transmembrane protein which adopts a number of different conformations .
Peptidase M48 (Peptidase_M48)
Type: Domain

This entry represents the largely extracellular catalytic region of CAAX prenyl protease homologues such as Human FACE-1 protease. These are metallopeptidases, with the characteristic HExxH motif giving the two histidine-zinc-ligands and an adjacent glutamate on the next helix being the third. The whole molecule folds to form a deep groove/cleft into which the substrate can fit .

This group of metallopeptidases belong to MEROPS peptidase family M48. Proteins with this domain are mostly described as probable protease htpX homologue (

) or CAAX prenyl protease 1, which proteolytically removes the C-terminal three residues of farnesylated proteins. They are integral membrane proteins associated with the endoplasmic reticulum and Golgi, binding one zinc ion per subunit.
Glycoside hydrolase, family 22 (Glyco_hydro_22)
Type: Family

Glycoside hydrolase family 22

comprises enzymes with two known activities; lysozyme type C (

) (also known as 1, 4-beta-N-acetylmuramidase or LYZ) and alpha-lactalbumins (also known as lactose synthase B protein or LA). Asp and/or the carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base.

Alpha-lactalbumin is a milk protein that acts as the regulatory subunit of lactose synthetase, acting to promote the conversion of galactosyltransferase to lactose synthase, which is essential for milk production. In the mammary gland, alpha-lactalbumin changes the substrate specificity of galactosyltransferase from N-acetylglucosamine to glucose.

Lysozymes (

) act as bacteriolytic enzymes by hydrolyzing the beta(1->4) bonds between N-acetylglucosamine and N-acetylmuramic acid in the peptidoglycan of prokaryotic cell walls. It has also been recruited for a digestive role in certain ruminants and colobine monkeys . There are at least five different classes of lysozymes : C (chicken type), G (goose type), phage-type (T4), fungi (Chalaropsis), and bacterial (Bacillus subtilis). There are few similarities in the sequences of the different types of lysozymes.

Lysozyme type C and alpha-lactalbumin are similar both in terms of primary sequence and structure, and probably evolved from a common ancestral protein . Around 35 to 40% of the residues are conserved in both proteins as well as the positions of the four disulphide bonds. There is, however, no similarity in function. Another significant difference between the two enzymes is that all lactalbumins have the ability to bind calcium , while this property is restricted to only a few lysozymes .

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.
Aminotransferase, class-II, pyridoxal-phosphate binding site (Aminotrans_II_pyridoxalP_BS)
Type: Binding_site

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. One of these, is called class-II. It consists of Serine palmitoyltransferase (

), Histidinol-phosphate aminotransferase (

), Glycine acetyltransferase

), 5-aminolevulinic acid synthase (

) and 8-amino-7-oxononanoate synthase (

).

The crystal structures of a number of the aminotransferases have been determined including the structure of l-histidinol phosphate aminotransferase from Escherichia coli (HisC) . HisC is a dimeric enzyme with a mass of approximately 80kDa. Like most pyridoxal-5'-phosphate (PLP)-dependent enzymes, each HisC monomer consists of two domains, a larger PLP-binding domain having an α/β/α topology, and a smaller domain. The N-terminal arm contributes to the dimerization of the two monomers. The PLP-binding domain of HisC shows weak sequence similarity, but significant structural similarity with the PLP-binding domains of a number of PLP-dependent enzymes.
Carbohydrate-binding type-2 domain (CBD2)
Type: Domain

The microbial degradation of cellulose and xylans requires several types of enzyme such as endoglucanases (EC 3.2.1.4), cellobiohydrolases (EC 3.2.1.91) (exoglucanases), or xylanases (EC 3.2.1.8) . Structurally, cellulases and xylanases generally consist of a catalytic domain and a conserved region of ~100 amino acid residues, the carbohydrate-binding module 2 (CBM2) . It is found either at the N-terminal or at the C-terminal extremity of these enzymes.

CBM2 can be classified in 2 subfamilies according to substrate specificities: CBM2a which binds cellulose and CBM2b which interacts specifically with xylan. Like other CBM domains CBM2 is a β-sheet domain containing a planar face which interacts with its ligand via a hydrophobic strip of aromatic residues . In family 2a this hydrophobic surface consists of three tryptophan residues, which are all required for binding soluble and insoluble forms of cellulose . In family 2b only 2 surface-exposed tryptophans are conserved and the first one is oriented differently. It is therefore not well oriented to interact with cellulose but is ideal for binding xylan .

This domain recognises both CBM2 subfamilies.
Asp/Glu racemase (Asp/Glu_race)
Type: Homologous_superfamily

Aspartate racemase (

) and glutamate racemase (

) are two evolutionary related bacterial enzymes that do not seem to require a cofactor for their activity . Glutamate racemase catalyses the interconversion of d-and l-glutamic acid and is the source of d-glutamate in most bacterial strains. d-Glutamic acid is an important biosynthetic building block since it is required in the formation of peptidoglycan that protects bacteria from osmotic lysis. Two conserved cysteines are present in the sequence of these enzymes. They are expected to play a role in catalytic activity by acting as bases in proton abstraction from the substrate .

Glutamate racemase forms a dimer and each monomer consists of two α/β fold domains .
Large ribosomal subunit protein eL8, eukaryota (Ribosomal_eL8_euk)
Type: Family

This family includes the large ribosomal subunit protein eL8 from human, which was formerly known as L7a, and its homologues . The human gene resembles other mammalian ribosomal protein genes so far, as it contains a short first exon, a short 5' untranslated leader and its transcriptional start sites at C residues embedded in a poly-pyrimidine tract .

The sequence of a gene for ribosomal protein eL8 (also known as L4) of Saccharomyces cerevisiae (Baker's yeast) unlike most of its other ribosomal protein genes, has no intron . The single open reading frame is highly similar to mammalian ribosomal protein eL8.

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 .