SII-SWORD/CoKE huggingface dataset:
Helix-turn-helix protein RpiR (HTH_RpiR)
Type: Domain

This domain contains a helix-turn-helix motif . Every member of this family is N-terminal to a SIS domain

. Members of this family are probably regulators of genes involved in phosphosugar metobolism.
NADH:ubiquinone oxidoreductase, 75kDa subunit, conserved site (NADH_UbQ_OxRdtase_75kDa_su_CS)
Type: Conserved_site

This entry represents the 75kDa subunit from NADH:ubiquinone oxidoreductase. Among the many polypeptide subunits that make up complex I, there is one with a molecular weight of 75kDa (in mammals), which is the largest subunit of complex I and is a component of the iron-sulphur (IP) fragment of the enzyme. It seems to bind to two 4Fe-4S clusters (called N-3 and N-4).
Histone deacetylase HDAC (HDACs)
Type: Family

Histone deacetylases (HDACs)

are a class of enzymes that remove acetyl groups from N(6)-acetyl-lysine residues on histones. This process plays a critical role in transcription regulation, as HDACs facilitate tighter wrapping of DNA around histones. DNA expression is regulated in part by the balance between acetylation and deacetylation. The reaction catalyzed by HDACs is the reverse of

, which transfers acetyl groups to histones. In general, HDACs suppress gene expression because the removal of acetyl groups from the ε-amino group of lysine side chains at the N-terminal of histones restores the positive charge of lysine residues. This stabilization strengthens histone-DNA interactions and prevents transcription factors from binding to promoter elements . HDACs, along with acetoin utilization proteins and acetylpolyamine amidohydrolases, belong to an ancient protein superfamily .
HDAC can be divided by different classes :

Class I:
Includes HDAC1, HDAC2, HDAC3, and HDAC8. Generally nuclear and involved in transcriptional repression.

Class II:
Includes HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10. Can shuttle between the nucleus and cytoplasm and are involved in diverse cellular processes. Subdivided into IIa (HDAC4, 5, 7, 9) and IIb (HDAC6, 10).

Class III:
Sirtuins (SIRT1-7 in mammals). NAD+-dependent deacetylases with different enzymatic mechanisms, involved in aging, metabolism, and stress response. Often considered a separate family.

Class IV:
Includes HDAC11. Has characteristics of both Class I and II.
Small ribosomal subunit protein eS28 (Ribosomal_eS28)
Type: Family

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities. Examples are:

Mammalian S28

Plant S28

Fungi S33

Archaebacterial S28e.

These proteins have from 64 to 78 amino acids and a highly conserved C-terminal region.

S1-like RNA-binding domains are found in a wide variety of RNA-associated proteins. S28e protein is a component of the 30S ribosomal subunit. S28E is highly conserved among archaea and eukaryotes. S28E may control precursor RNA splicing and turnover in mRNA maturation process but its function in the ribosome is largely unknown. The structure contains an OB-fold found in many oligosaccharide and nucleic acid binding proteins. This implies that S28e might be involved in protein synthesis .

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 .
Colicin immunity protein/pyocin immunity protein (Colicin_pyocin)
Type: Family

This family includes bacterial colicin and pyocin immunity proteins . These immunity proteins can bind specifically to the DNase-type colicins and pyocins and inhibit their bactericidal activity. The 1.8-angstrom crystal structure of the ImmE7 protein consists of four antiparallel α-helices . Sequence similarities between colicins E2, A and E1 are less striking. The colicin E2 (pyocin) immunity protein does not share similarity with either the colicin E3 or cloacin DF13 immunity proteins. Pyocin protects a cell that harbours the plasmid ColE2 encoding colicin E2 against colicin E2; it is thus essential both for autonomous replication and colicin E2 immunity .
D-alanine--D-alanine ligase/VANA/B/C, conserved site (D-Ala_lig_Van_CS)
Type: Conserved_site

D-alanine--D-alanine ligase (

) is a bacterial enzyme involved in cell-wall biosynthesis. It participates in forming UDP-N-acetylmuramyl pentapeptide, the peptidoglycan precursor. These enzymes are proteins of 300 to 360 amino acids containing many conserved regions. The N-terminal Gly-rich region could be involved in ATP-binding .
Formate/nitrite transporter (For/NO2_transpt)
Type: Family

Proteins in this entry belong to the Formate-Nitrite Transporter (FNT) family (TC 2.A.44), including the nitrite transport protein NirC and formate channel FocA. The prokaryotic proteins of the FNT family function in the transport of the structurally related compounds, formate and nitrite . Structures from NirC and FocA showed that they have a pentameric architecture with structural similarity to aquaporins and glyceroporins, comprising a right-handed bundle of 6 transmembrane (TM) α-helices . The homologous yeast protein may function as a short chain aliphatic carboxylate H+ symporter, transporting formate, acetate and propionate, and functioning primarily as an acetate uptake permease.
Channel forming colicin, C-terminal cytotoxic (Channel_colicin_C)
Type: Domain

Colicins are plasmid-encoded polypeptide toxins produced by and active against Escherichia coli and closely related bacteria. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them to translocate to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.

Channel-forming colicins (colicins A, B, E1, Ia, Ib, and N) are transmembrane proteins that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy . These colicins contain at least three domains: an N-terminal translocation domain responsible for movement across the outer membrane and periplasmic space; a central domain responsible for receptor recognition; and a C-terminal cytotoxic domain responsible for channel formation in the cytoplasmic membrane .

This entry represents the C-terminal cytotoxic domain, which has a globin-like fold with additional helices at either end.
Gamma-carboxyglutamic acid-rich (GLA) domain (GLA_domain)
Type: Domain

The GLA (gamma-carboxyglutamic acid-rich) domain contains glutamate residues that have been post-translationally modified by vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla) . All glutamic acid (Glu) residues present in the GLA domain are potential carboxylation sites; in coagulation proteins, all Gu residues are modified to Gla, while in osteocalcin and matrix Gla proteins only some Glu residues are modified to Gla.
Cation-dependent mannose-6-phosphate receptor (Man-6-P_rcpt_cation_dep)
Type: Family

The cation dependent mannose-6-phosphate (man-6-P) receptor is one of two transmembrane proteins involved in the transport of lysosomal enzymes from the Golgi complex and the cell surface to lysosomes . Lysosomal enzymes bearing phosphomannosyl residues bind specifically to man-6-P receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment, where the low pH mediates dissociation of the complex. Binding is optimal in the presence of divalent cations.

The amino acid sequence is a single polypeptide chain that contains a putative signal sequence and a transmembrane domain . The cation-dependent mannose 6-phosphate (M6P) receptor (CD-MPR) is present predominantly as a stable homodimer in membranes and has a single M6P-binding site per polypeptide . The molecule crystallizes as a homodimer with approximately 20% of the entire surface area of each monomer having contact with another through predominantly hydrophobic interactions . Each monomer contains a single α-helix near its amino terminus followed by nine primarily anti-parallel β-strands that form two β-sheets, which are positioned orthogonally to each other. Extensive hydrophobic interactions are formed between the two β-sheets, which results in each monomer forming a flattened β-barrel structure. Six cysteine residues form three intramolecular disulphide bonds that are essential for the ligand-binding conformation of the receptor to be generated. The structures of the liganded molecules show that the carbohydrate-recognition domain of the enzyme lies relatively deep inside the protein, so that the terminal M6P residue and the penultimate sugar ring of bound pentamannosyl phosphate are mostly buried in the receptor. This deep binding pocket facilitates the formation of numerous interactions between the CD-MPR and its carbohydrate ligands.
Peptidyl-prolyl cis-trans isomerase, PpiC-type (PPIase_PpiC)
Type: Domain

Peptidyl-prolyl cis-trans isomerase (

) (PPIase or rotamase) is an enzyme that accelerates protein folding by catalysing the cis-trans
isomerisation of proline imidic peptide bonds in oligopeptides . Most characterised PPiases belong to two families, the cyclophilin-type and the the FKBP-type. A third family has been discovered . So far, the only biochemically characterised member of this family is the Escherichia coli protein parvulin (gene ppiC), a small (92 residues) cytoplasmic enzyme that prefers amino acid residues with hydrophobic side chains like leucine and phenylalanine in the P1 position of the peptides substrates.

This entry represents a conserved region that contains a serine which could play a role in the catalytic mechanism of these enzymes. This domain is present in Periplasmic chaperone PpiD that were originally thought to be peptidyl-prolyl isomerases but it was shown later that they lack such activity .
Cytochrome c oxidase subunit III-like (Cyt_c_oxidase-like_su3)
Type: Domain

This entry represents a structural domain found in cytochrome c and ubiquinol oxidase subunit III. The overall structure of these enzymes is similar .

Cytochrome c oxidase (

) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyses the transfer of electrons from reduced cytochrome c to molecular oxygen:

4 cytochrome c
+2
+ 4 H
+
+ O
2
--> 4 cytochrome c
+3
+ 2 H
2
O

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane .

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small polypeptidic subunits . The functional role of subunit III is not yet understood.

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Even though the cytochrome o complex oxidises quinol (ubiquinol) and does not catalyse the oxidation of reduced cytochrome c, they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved .
Inositol polyphosphate-related phosphatase (IPPc)
Type: Domain

This domain is found in diverse proteins homologous to inositol monophosphatase .
These proteins are Mg
2+
-dependent/Li
+
-sensitive phosphatases that catalyse a variety of reactions.
Tetraspanin, animals (Tetraspanin_animals)
Type: Family

Tetraspanins are a distinct family of cell surface proteins, containing four conserved transmembrane domains: a small outer loop (EC1), a larger outer loop (EC2), a small inner loop (IL) and short cytoplasmic tails. They contain characteristic structural features, including 4-6 conserved extracellular cysteine residues, and polar residues within transmembrane domains.

A fundamental role of tetraspanins appears to be organising other proteins into a network of multimolecular membrane microdomains, sometimes called the 'tetraspanin web'. Within this web there are primary complexes in which tetraspanins show robust, specific, and direct lateral associations with other proteins. The strong tendency of tetraspanins to associate with each other probably contributes to the assembly of a network of secondary interactions in which non-tetraspanin proteins are associated with each other via palmitoylated tetraspanins acting as linker proteins. In addition, the association of lipids, such as gangliosides and cholesterol, probably contributes to the assembly of even larger tetraspanin complexes, which have some lipid raft-like properties (e.g. resistance to solubilization in non-ionic detergents). Within the tetraspanin web, tetraspanin proteins can associate not only with integrins and other transmembrane proteins, but also with signalling enzymes such as protein kinase C and phosphatidylinositol-4 kinase. Thus, the tetraspanin web provides a mechanistic framework by which membrane protein signalling can be expanded into a lateral dimension .
Pyrroline-5-carboxylate reductase-like (Pyrroline-COOH_reductase)
Type: Family

Pyrroline-5-carboxylate reductase (P5CR) (

) is the enzyme that catalyses the terminal step in the biosynthesis of proline from glutamate, the NAD(P) dependent oxidation of 1-pyrroline-5-carboxylate into proline. This enzyme is also able to convert delta-1-piperideine-6-carboxylate (P6C) into pipecolic acid ; this activity is part of pathway for the biosynthesis of the cyclic tetrapeptide apicidin F in the fungus Fusarium fujikuroi . This entry also includes the pyrroline-5-carboxylate reductase ucsG from Acremonium sp., which is part of the gene cluster that mediates the biosynthesis of UCS1025A, a member of the pyrrolizidinone family that is a strong telomerase inhibitor and displays potent antibacterial and antitumor properties . This entry also includes Delta-1-pyrroline-5-carboxylate reductase kk1I, part of the gene cluster that mediates the biosynthesis of KK-1, a novel cyclic depsipeptide with 10 residues which is a promising active compound with high activity against many plant pathogens, especially Botrytis cinerea .
GIY-YIG endonuclease (GIY-YIG_endonuc)
Type: Domain

Nucleases of the GIY-YIG family are involved in many cellular processes, including DNA repair and recombination, transfer of mobile genetic elements, and restriction of incoming foreign DNA. The GIY-YIG superfamily groups together nucleases characterised by the presence of a domain of typically ~100 amino acids, with two short motifs "GIY" and "YIG" in the N-terminal part, followed by an Arg residue in the centre and a Glu residue in the C-terminal part .

The GIY-YIG domain forms a compact structural domain, which serves as a scaffold for the coordination of a divalent metal ion required for catalysis of the phosphodiester bond cleavage. The GIY-YIG domain has an α/β-sandwich architecture with a central three-stranded antiparallel β-sheet flanked by three-helices. The three-stranded antiparallel β-sheet contains the GIY-YIG sequence elements. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site .

The GIY-YIG domain has been implicated in a variety of cellular processes involving DNA cleavage, from self-propagation with or without introns, to restriction of foreign DNA, to DNA repair and maintenance of genome stability .

Some proteins known to contain a GIY-YIG domain include:

Eukaryotic Slx-1 proteins, involved in the maintenance of the rDNA copy number. They have a C-terminal RING finger Zn-binding domain.

Mammalian ankyrin repeat and LEM domain- containing protein 1 (ANKLE1).

Bacterial and archaeal UvrC subunits of (A)BC excinucleases, which remove damaged nucleotides by incising the damaged strand on both sides of the lesion.

Phage T4 endonucleases SegA to E, probably involved in the movement of the endonuclease-encoding DNA.

Phage T4 intron-associated endonuclease 1 (I-TevI), specific to the thymidylate synthase (td) gene splice junction and involved in intron homing.
FYVE zinc finger (Znf_FYVE)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two zinc ions . The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. FYVE-type domains are divided into two known classes: FYVE domains that specifically bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related domains of undetermined function . Those that bind to phosphatidylinositol 3-phosphate are often found in proteins targeted to lipid membranes that are involved in regulating membrane traffic . Most FYVE domains target proteins to endosomes by binding specifically to phosphatidylinositol-3-phosphate at the membrane surface. By contrast, the CARP2 FYVE-like domain is not optimized to bind to phosphoinositides or insert into lipid bilayers. FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif, a basic R(R/K)HHCR patch, and a C-terminal RVC motif.
Small ribosomal subunit protein bS16 (Ribosomal_bS16)
Type: Family

Ribosomal protein S16 (also known as bS16) is one of the proteins from the small ribosomal subunit. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:

Eubacterial S16.

Algal and plant chloroplast S16.

Cyanelle S16.

Neurospora crassa mitochondrial S24 (cyt-21).

S16 proteins have about 100 amino-acid residues. There are two paralogues in Arabidopsis thaliana, RPS16-1 (chloroplastic) and RPS16-2 (targeted to the chloroplast and the mitochondrion) .

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 .