SII-SWORD/CoKE huggingface dataset:
GRIP domain (GRIP_dom)
Type: Domain

The GRIP (golgin-97, RanBP2alpha,Imh1p and p230/golgin-245) domain is found in many large coiled-coil proteins. It has been shown to be sufficient for targeting to the Golgi . The GRIP domain contains a completely conserved tyrosine residue.
Ribosome-binding factor A (RbfA)
Type: Family

Ribosome-binding factor A (gene rbfA) is a bacterial protein that associates with free 30S ribosomal subunits. It does not associate with 30S subunits that are part of 70S ribosomes or polysomes. It is essential for efficient processing of 16S rRNA. Ribosome-binding factor A is a protein of from 13 to 15 Kd which is found in most bacteria. A putative chloroplastic form seems to exist in plants.

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 .
GPCR kinase (GPCR_kinase)
Type: Family

Rapid regulation of G-protein-coupled receptors (GPCRs) involves agonist- promoted receptor phosphorylation by GPCR kinases (GRKs) . This process is followed by arrestin binding and transient receptor internalisation. It has been shown that beta-adrenergic receptor kinase (beta ARK-1 or GRK2) follows a similar pattern of internalisation upon agonist activation of beta(2)-adrenergic receptors (beta(2)AR) and that beta ARK expression levels modulate receptor sequestration . Such studies indicate a functional relationship between receptor phosphorylation and sequestration, showing that beta ARK not only translocates from the cytoplasm to the plasma membrane in response to receptor occupancy, but also shares endocytic mechanisms with the beta(2)AR . These results suggest a role for beta ARK in the sequestration process, or involvement of receptor internalisation in the intracellular trafficking of the kinase .
Serpin B9/maspin (Serpin_B9/Maspin)
Type: Family

This family consists of serpin B5 (Maspin) and serpin B9. They are members of the serpin (SERine Protease INhibitor) family (MEROPS inhibitor family I4, clan ID).
Ribosomal RNA large subunit methyltransferase K/L-like, methyltransferase domain (RlmKL-like_Mtase)
Type: Domain

This entry represents the methyltransferase domain found in ribosomal RNA large subunit methyltransferase K/L from Escherichia coli (RmlKL) and tRNA (guanine(10)-N2)-dimethyltransferase from Methanocaldococcus jannaschii which is associated with the THUMP domain (

) RmlKL specifically methylates the guanine in positions 2445 and 2069 of 23S rRNA before its assembly into 50S subunits .
Tyrosine-specific protein phosphatase, PTPase domain (PTP_cat)
Type: Domain

This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases).

Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. The cytoplasmic region generally contains two copies of the PTPase domain. The first seems to have enzymatic activity, while the second is inactive. The inactive domains of tandem phosphatases can be divided into two classes. Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. There is a region of higher conservation common to both classes, suggesting a new regulatory centre . PTPase domains consist of about 300 amino acids. There are two conserved cysteines, the second one has been shown to be absolutely required for activity. Furthermore, a number of conserved residues in its immediate vicinity have also been shown to be important.

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;

) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation . The PTP superfamily can be divided into four subfamilies :

(1) pTyr-specific phosphatases

(2) dual specificity phosphatases (dTyr and dSer/dThr)

(3) Cdc25 phosphatases (dTyr and/or dThr)

(4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

Receptor-like, which are transmembrane receptors that contain PTPase domains

Non-receptor (intracellular) PTPases

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif . Functional diversity between PTPases is endowed by regulatory domains and subunits.
Peptidase T1A, proteasome beta-subunit (Pept_T1A_subB)
Type: Family

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. In eukaryotes the proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Most proteasome subunits can be classified, on the basis on sequence similarities into two groups, alpha (A) and beta (B). These are arranged in four rings of seven proteins, consisting of a ring of alpha subunits, two rings of beta subunits, and a ring of alpha subunits. In eukaryotes, each alpha and each beta ring consists of different proteins. Three of the beta subunits are peptidases in subfamily T1A, and each has a distinctive specificity (trypsin-like, chymotrypsin-like and glutamyl peptidase-like). The peptidases are N-terminal nucleophile hydrolases in which the N-terminal threonine is the nucleophile in the hydrolytic reaction . In the immunoproteasome, the catalytic components are replaced by three specialist, catalytic beta subunits . In bacteria and archaea there is only one alpha subunit and one beta subunit, and each ring is a homoseptamer.
Large ribosomal subunit protein bL9 (Ribosomal_bL9)
Type: Family

This entry represents the large ribosomal subunit protein bL9. In Escherichia coli, bL9 is known to bind directly to the 23S rRNA. It belongs to a family of ribosomal proteins grouped on the basis of sequence similarities .

The crystal structure of Bacillus stearothermophilus bL9 shows the 149-residue protein comprises two globular domains connected by a rigid linker . Each domain contains an rRNA binding site, and the protein functions as a structural protein in the large subunit of the ribosome. The C-terminal domain consists of two loops, an α-helix and a three-stranded mixed parallel, anti-parallel β-sheet packed against the central α-helix. The long central α-helix is exposed to solvent in the middle and participates in the hydrophobic cores of the two domains at both ends.

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 .
V-ATPase proteolipid subunit (ATPase_proteolipid_csu)
Type: Family

This entry represents the 16kDa proteolipid subunit c that is part of the V0 complex of V-ATPase in eukaryotic organelles and in certain bacteria. There are three proteolipid subunits (known as c, c' and c'' in yeast) that form part of the proton-conducting pore, each containing a buried glutamic acid residue that is essential for proton transport, and together they form a hexameric ring spanning the membrane .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
Peptidase T2, asparaginase 2 (Peptidase_T2)
Type: Family

This protein family represents a group of Ntn-hydrolases from all cellular organisms that belong to the MEROPS peptidase family T2 (clan PB(T)). Members of this entry include glycosylasparaginases (

), which are threonine peptidases, and L-asparaginases (

).

Glycosylasparaginases are characterised by a threonine nucleophile at the N terminus of the mature enzyme. They catalyse:

N4-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H(2)O = N-acetyl-beta-glucosaminylamine + L-aspartate

It cleaves the GlcNAc-Asn bond that links oligosaccharides to asparagine in N-linked glycoproteins. The enzyme is composed of two non-identical alpha/beta subunits joined by strong non-covalent forces, has one glycosylation site located in the alpha subunit and plays a major role in the degradation of glycoproteins.

L-asparaginases catalyse the following reaction:

L-asparagine + H
2
O = L-aspartate + NH
3
Cucumovirus coat protein (Cucumovirus_coat)
Type: Family

Cucumoviruses are tripartite RNA plant viruses believed to share a close evolutionary relationship with Brome mosaic virus (BMV). The cucumoviruses include: Cucumber mosaic virus , Peanut stunt virus and Tomato aspermy virus . The viral coat proteins show a high degree of sequence similarity .
Angiotensin II receptor family (ATII_rcpt)
Type: Family

Angiotensin II is a blood-borne hormone produced in the circulation, it is also formed in many tissues such as the brain, kidney, heart, and blood vessels, where angiotensin II functions as a paracrine and autocrine hormone. The known actions of angiotensin II are mediated through two angiotensin receptor subtypes, Angiotensin II receptor 1 and angiotensin II receptor 2, which are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family. These subtypes are important in the renin-angiotensin system, as they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II . They also stimulate increased fluid intake and regulate the neuroendocrine system .

This entry represents the angiotensin II receptor family. It also includes the relaxin-3 receptor 2, also known as GPCR142 , and the apelin receptor from lower vertebrates .
Bacterial microcompartment domain (BMC_dom)
Type: Domain

Bacterial microcompartments (BMCs) are large proteinaceous structures comprised of a roughly icosahedral shell and a series of encapsulated enzymes. The shells of BMCs are made primarily of a family of proteins whose structural core is the BMC domain, and variations upon this core provide functional diversity. This domain is found in a variety of polyhedral organelle shell proteins (CcmK), including CsoS1A, CsoS1B and CsoS1C of Thiobacillus neapolitanus (Halothiobacillus neapolitanus) and their orthologues from other bacteria .

Some autotrophic and non-autotrophic organisms form polyhedral organelles, carboxysomes/enterosomes . The best studied is the carboxysome of Halothiobacillus neapolitanus, which is composed of at least 9 proteins: six shell proteins, CsoS1A, CsoS1B, CsoS1C, Cso2A, Cso2B and CsoS3 (carbonic anhydrase) , one protein of unknown function and the large and small subunits of RuBisCo (CbbL and Cbbs). Carboxysomes appear to be approximately 120 nm in diameter, most often observed as regular hexagons, with a solid interior bounded by a unilamellar protein shell. The interior is filled with type I RuBisCo, which is composed of 8 large subunits and 8 small subunits; it accounts for 60% of the carboxysomal protein, which amounts to approximately 300 molecules of enzyme per carboxysome. Carboxysomes are required for autotrophic growth at low CO
2
concentrations and are thought to function as part of a CO
2
-concentrating mechanism .

Polyhedral organelles, enterosomes, from non-autotrophic organisms are involved in coenzyme B
12
-dependent 1,2-propanediol utilisation (e.g., in Salmonella enterica ) and ethanolamine utilisation (e.g., in Salmonella typhimurium ). Genes needed for enterosome formation are located in the 1,2-propanediol utilisation
pdu
or ethanolamine utilisation
eut
operons, respectively. Although enterosomes of non-autotrophic organisms are apparently related to carboxysomes structurally, a functional relationship is uncertain. A role in CO
2
concentration, similar to that of the carboxysome, is unlikely since there is no known association between CO
2
and coenzyme B12-dependent 1,2-propanediol or ethanolamine utilisation . It seems probable that enterosomes help protect the cells from reactive aldehyde species in the degradation pathways of 1,2-propanediol and ethanolamine .

The BMC domain fold consists of three α-helices (designated A, B, and C) and four β-strands (

). Some instances of the BMC shell protein reveal a circular permutation in which a highly similar tertiary structure is built from secondary structure elements occurring in a different order. The secondary structure elements contributed by the C-terminal region of the typical BMC fold are instead contributed by the N-terminal region of the BMC circularly permuted domain (

) .
Peptidase G1 (Peptidase_G1)
Type: Family

The peptidases in family G1 form a subset of what were formerly termed 'pepstatin-insensitive carboxyl proteinases'. After its discovery in about 1970, the pentapeptide pepstatin soon came to be thought of as a very general inhibitor of the endopeptidases that are active at acidic pH. But more recently several acid-acting endopeptidases from bacteria and fungi had been found to be resistant to pepstatin. The unusual active sites of the 'pepstatin-insensitive carboxyl peptidases' proved difficult to characterise, but it has now been established that the enzymes from bacteria are acid-acting serine peptidases in family S53 (clan SB),

, whereas the fungal enzymes are in family G1 (formerly A4) . The importance of glutamate ('E') and glutamine ('Q') residues in the active sites of the family G1 enzymes led to the family name, Eqolisin .

This group of glutamate/glutamine peptidases belong to MEROPS peptidase family G1 (eqolisin family, clan GA). An example of this group is scytalidoglutamic peptidase. The proteins are thermostable, pepstatin insensitive and are active at low pH ranges . The enzyme has a unique heterodimeric structure, with a 39-residue light chain and a 173-residue heavy chain bound to each other non-covalently . The tertiary structure of the active site of scytalidoglutamic peptidase (MEROPS G01.001) with a bound tripeptide product has been interpreted as showing that Glu136 is the primary catalytic residue. The most likely mechanism is suggested to be nucleophilic attack by a water molecule activated by the Glu136 side chain on the si-face of the scissile peptide bond carbon atom to form the tetrahedral intermediate. Electrophilic assistance, and oxyanion stabilisation, are provided by the side-chain amide of Gln53.

Both scytalidoglutamic peptidase (MEROPS G01.001) and aspergilloglutamic peptidase (MEROPS G01.002) cleave the Tyr26 Thr27 bond in the B chain of oxidized insulin; a bond not cleaved by other acid-acting endopeptidases. Scytalidoglutamic peptidase is most active on casein at pH 2 and is inhibited by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP), a compound that also inhibits pepsin.
Forkhead-associated (FHA) domain (FHA_dom)
Type: Domain

The forkhead-associated (FHA) domain is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity. It spans approximately 80-100 amino acid residues folded into an 11-stranded β-sandwich, which sometimes contain small helical insertions between the loops connecting the strands .

To date, genes encoding FHA-containing proteins have been identified in eubacterial and eukaryotic but not archaeal genomes. The domain is present in a diverse range of proteins, such as kinases, phosphatases, kinesins, transcription factors, RNA-binding proteins and metabolic enzymes which partake in many different cellular processes - DNA repair, signal transduction, vesicular transport and protein degradation are just a few examples.
Cellulose-binding domain (CBD)
Type: Domain

This entry represents the cellulose-binding domain (CBD) in monooxygenase, exoglucanase, cellobiohydrolase, endoglucanases and related enzymes, mainly from fungi.

The microbial degradation of cellulose and xylans requires several types of enzymes, such as endoglucanases (

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Structurally, cellulases and xylanases generally consist of a catalytic domain joined to a CBD by a short linker sequence rich in proline and/or hydroxy-amino acids. The CBD of several fungal cellulases has been shown to consist of 36 amino acid residues, and it is found either at the N-terminal or at the C-terminal extremity of the enzymes. As it is shown in the following schematic representation, there are four conserved cysteines in this type of CBD domain, all involved in disulphide bonds.

+----------------+
| +-----|---------+
| | | |
xxxxxxxCxxxxxxxxxxCxxxxxCxxxxxxxxxCx
Influenza A virus NS1 protein (NS1A)
Type: Family

NS1 is a homodimeric RNA-binding protein found in influenza virus that is required for viral replication. NS1 binds polyA tails of mRNA keeping them in the nucleus. NS1 inhibits pre-mRNA splicing by tightly binding to a specific stem-bulge of U6 snRNA .
Uroporphyrinogen decarboxylase (URO-D) (Uroporphyrinogen_deCOase)
Type: Domain

Uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the haem biosynthetic pathway, catalyses the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen . URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP). The sequence of URO-D has been well conserved throughout evolution. The best conserved region is located in the N-terminal section; it contains a perfectly conserved hexapeptide. There are two arginine residues in this hexapeptide which could be involved in the binding, via salt bridges, to the carboxyl groups of the propionate side chains of the substrate.

The crystal structure of human uroporphyrinogen decarboxylase shows it as comprised of a single domain containing a (β/α)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. URO-D is a dimer in solution. Dimerisation juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centres .