SII-SWORD/CoKE huggingface dataset:
Ada DNA repair, metal-binding (Ada_DNA_repair_Zn-bd)
Type: Domain

The Escherichia coli Ada protein repairs O6-methylguanine residues and methyl phosphotriesters in DNA by direct transfer of the methyl group to a cysteine residue. This domain contains four conserved cysteines that form a zinc binding site . One of these cysteines is a methyl group acceptor. The methylated domain can then specifically bind to the ada box on a DNA duplex. The zinc binding site is located in the N-terminal region and consists of four β strands .
SEC-C motif (SEC_C_motif)
Type: Conserved_site

The SEC-C motif found in the C terminus of the SecA protein, in the middle of some SWI2 ATPases and also solo in several proteins. The motif is predicted to chelate zinc with the CXC and C[HC] pairs that constitute the most conserved feature of the motif. It is predicted to be a potential nucleic acid binding domain.
Retroviral Gag polyprotein, M (Gag_M)
Type: Domain

The Gag polyprotein directs the assembly and release of virus particles from infected cells. The Gag polyprotein has three domains required for activity: an N-terminal membrane-binding (M) domain that directs Gag to the plasma membrane, an interaction (I) domain involved in Gag aggregation, and a late assembly (L) domain that mediates the budding process . During viral maturation, the Gag polyprotein is then cleaved into major structural proteins by the viral protease, yielding the matrix, capsid, nucleoprotein, and some smaller peptides. In Rous sarcoma virus (RSV), the M domain consists of the first 85 residues of the matrix protein. However, unlike other Gag polyproteins, the M domain of RSV Gag is not myristylated, but retains full activity .This domain forms an α helical bundle structure .

This entry represents the M domain of the Gag polyprotein found in avian retroviruses. This entry also identifies Gag polyproteins from several avian endogenous retroviruses, which arise when one or more copies of the retroviral genome becomes integrated into the host genome .
UreE urease accessory, N-terminal (UreE_N)
Type: Domain

The N-terminal domain is termed the peptide-binding domain. Deletion of this domain does not eliminate enzymatic activity, and the truncated protein can still activate urease .

Urease and other nickel metalloenzymes are synthesised as precursors devoid of the metalloenzyme active site. These precursors then undergo a complex post-translational maturation process that requires a number of accessory proteins.

Members of this group are nickel-binding proteins required for urease metallocentre assembly . They are believed to function as metallochaperones to deliver nickel to urease apoprotein . It has been shown by yeast two-hybrid analysis that UreE forms a dimeric complex with UreG in Helicobacter pylori . The UreDFG-apoenzyme complex has also been shown to exist and is believed to be, with the addition of UreE, the assembly system for active urease . The complexes, rather than the individual proteins, presumably bind to UreB via UreE/H recognition sites.

The structure of Klebsiella aerogenes UreE reveals a unique two-domain architecture.The N-terminal domain is structurally related to a heat shock protein, while the C-terminal domain shows homology to the Atx1 copper metallochaperone . Significantly, the metal-binding sites in UreE and Atx1 are distinct in location and types of residues despite the relationship between these proteins and the mechanism for UreE activation of urease is proposed to be different from the thiol ligand exchange mechanism used by the copper metallochaperones.
Nitric oxide synthase, N-terminal (NOS_N)
Type: Domain

This entry represents the N-terminal of the nitric oxide synthases.

Nitric oxide synthase (

) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed .

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria . Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (

). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation . The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain . Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain.
PMP-22/EMP/MP20/Claudin (PMP22/EMP/MP20/Claudin)
Type: Family

This family of evolutionarily related integral membrane proteins includes PMP22, EMP, claudins and voltage-gated calcium channel gamma subunits, many of which perform diverse functions at specialised cell-cell contacts . Family members from vertebrates and invertebrates are highly divergent.
PMP-22/EMP/MP20 (PMP22_EMP_MP20)
Type: Family

Several vertebrate small integral membrane glycoproteins are evolutionary related , including eye lens specific membrane protein 20 (MP20 or MP19); epithelial membrane protein-1 (EMP-1), which is also known as tumor-associated membrane protein (TMP) or as squamous cell-specific protein Cl-20; epithelial membrane protein-2 (EMP-2), which is also known as XMP; epithelial membrane protein-3 (EMP-3), also known as YMP; and peripheral myelin protein 22 (PMP-22), which is expressed in many tissues but mainly by Schwann cells as a component of myelin of the peripheral nervous system (PNS). PMP-22 probably plays a role both in myelinization and in cell proliferation. Mutations affecting PMP-22 are associated with hereditary motor and sensory neuropathies such as Charcot-Marie-Tooth disease type 1A (CMT-1A) in human or the trembler phenotype in mice. The proteins of this family are about 160 to 173 amino acid residues in size, and contain four transmembrane segments. PMP-22, EMP-1, -2 and -3 are highly similar, while MP20 is more distantly related.
UbiE/COQ5 methyltransferase (UbiE/COQ5_MeTrFase)
Type: Family

This entry represents a family of methyltransferases involved in the biosynthesis of menaquinone and ubiqinone. Some members such as the UbiE enzyme from E. coli are believed to act in both pathways, while others may act in only the menaquinone pathway. These methyltransferases are members of the UbiE/CoQ family of methyltransferases which also contains ubiquinone methyltransferases and other methyltransferases. Members of this clade include a wide distribution of bacteria and eukaryotes, but no archaea. An outgroup for this clade is provided by the phosphatidylethanolamine methyltransferase (

) from Rhodobacter sphaeroides . Note that a number of non-orthologous genes which are members of

have been erroneously annotated as MenG methyltransferases.
Endonuclease III, iron-sulphur binding site (Endouclease-III_FeS-bd_BS)
Type: Binding_site

Endonuclease III is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a beta-elimination mechanism . The structurally related DNA glycosylase MutY recognises and excises the mutational intermediate 8-oxoguanine-adenine mispair . The 3-D structures of Escherichia coli endonuclease III and catalytic domain of MutY have been determined. The structures contain two all-alpha domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key, four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the Fe4S4 cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is referred to as a Fe4S4 cluster loop (FCL) . Two DNA-binding motifs have been proposed, one at either end of the interdomain groove: the helix-hairpin-helix (HhH) region (see

) and FCL motif, described in this entry. The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif .
Endonuclease III-like, conserved site-2 (Endonuclease-III-like_CS2)
Type: Conserved_site

Endonuclease III is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a beta-elimination mechanism . The structurally related DNA glycosylase MutY recognises and excises the mutational intermediate 8-oxoguanine-adenine mispair . The 3-D structures of Escherichia coli endonuclease III and catalytic domain of MutY have been determined. The structures contain two all-alpha domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key, four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the Fe4S4 cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is referred to as a Fe4S4 cluster loop (FCL) . Two DNA-binding motifs have been proposed, one at either end of the interdomain groove: the helix-hairpin-helix (HhH) (see

) and FCL motifs (see

). The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif .
Large ribosomal subunit protein eL8-like, conserved site (Ribosomal_eL8-like_CS)
Type: Conserved_site

This entry includes large ribosomal subunit protein eL8 (in human is also known as L7a and in yeast is also known as L4) and several other ribosomal proteins that have been found to share sequence similarity with eL8/L7a, including Saccharomyces cerevisiae NHP2 , NHP2-like proteins and Bacillus subtilis RNA-binding protein YlxQ, which recognizes the K-turn motif present in ribosomal RNA, but also in box C/D and box C'/D' sRNAs .

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 .
Ribosomal protein eL8/eL30/eS12/Gadd45 (Ribosomal_eL8/eL30/eS12/Gad45)
Type: Domain

This family includes: the metazoan large ribosomal subunit protein eL8 (known as L7A), the fungal ribosomal eL8-A and eL8-B, the eukaryotic small ribosomal subunit protein eS12 (known as S12), the eukaryotic and archaeal large ribosomal subunit protein eL30 (known as L30), Gadd45 and other closely related 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 .
NAF domain (NAF_dom)
Type: Domain

The NAF domain is a 24 amino acid domain that is found in a plant-specific subgroup of serine-threonine protein kinases (CIPKs), that interact with calcineurin B-like calcium sensor proteins (CBLs). Whereas the N-terminal part of CIPKs comprises a conserved catalytic domain typical of Ser-Thr kinases, the much less conserved C-terminal domain appears to be unique to this subgroup of kinases. The only exception is the NAF domain that forms an 'island of conservation' in this otherwise variable region. The NAF domain has been named after the prominent conserved amino acids Asn-Ala-Phe. It represents a minimum protein interaction module that is both necessary and sufficient to mediate the interaction with the CBL calcium sensor proteins .

The secondary structure of the NAF domain is currently not known, but secondary structure computation of the C-terminal region of Arabidopsis thaliana CBL-interacting protein kinase 1 revealed a long helical structure .
Intein DOD homing endonuclease, central region (Intein_endonuc_central)
Type: Domain

Inteins (for INternal proTEINs) are in frame intervening sequences that disrupt the coding region of a host gene. They are post-translationally excised from a protein precursor by a self-catalytic protein splicing process . Most inteins are bifunctional proteins mediating both protein splicing and DNA cleavage. The domain involved in splicing is formed by the two terminal splicing regions, which are separated by a small linker in mini-inteins or a 200- to 250-amino-acid homing endonuclease in larger inteins . Homing endonucleases are rare-cutting enzymes encoded by inteins and introns. By making a site-specific double-strand break in the intronless or inteinless alleles, these nucleases create recombinogenic ends which engage in a gene conversion process that duplicates the intron or intein . There are four families of homing endonucleases classified by conserved sequence motifs. Homing endonucleases found in inteins generally belong to the dodecapetide (DOD) family, but an HNH endonuclease is also found. Endonucleases of the DOD family contain one or two copies of a 10-residue sequence known as a dodecapeptide or LAGLIDADG motif. They recognise long, pseudopalindromic homing sites of 14-30 bp in length and cleave their homing site DNA to generate 4nt, 3' extensions. The DOD endonucleases found in inteins contain 2 dodecapeptide motifs and are active as monomers. Resolution of the 3D structure of PI-Sce revealed that the endonuclease domain consist of α/β motifs related by pseudo two-fold symmetry. The two α-helices containing the dodecapeptide motifs form the axis of symmetry .

This entry covers the conserved central intein Blocks C, D, E and H. Blocks C and E are the dodecapeptide motifs that are required for endonuclease activity and each contains an endonuclease active site Asp or Glu .
LCCL domain (LCCL)
Type: Domain

The LCCL domain has been named after the best characterised proteins that were found to contain it, namely Limulus factor C, Coch-5b2 and Lgl1. It is an about 100 amino acids domain whose C-terminal part contains a highly conserved histidine in a conserved motif YxxxSxxCxAAVHxGVI. The LCCL module is thought to be an autonomously folding domain that has been used for the construction of various modular proteins through exon-shuffling. It has been found in various metazoan proteins in association with complement B-type domains, C-type lectin domains, von Willebrand type A domains, CUB domains, discoidin lectin domains or CAP domains. It has been proposed that the LCCL domain could be involved in lipopolysaccharide (LPS) binding . Secondary structure prediction suggests that the LCCL domain contains six β strands and two α helices . The structure of the LCCL domain from human Coch-5b2 has been solved. It has an unusual fold, where a centrally located helix is wrapped by extended polypeptide segments of mostly irregular secondary structure .

Some proteins known to contain a LCCL domain include Limulus factor C, a LPS endotoxin-sensitive trypsin type serine protease which serves to protect the organism from bacterial infection; vertebrate cochlear protein cochlin or coch-5b2 (Cochlin is probably a secreted protein, mutations affecting the LCCL domain of coch-5b2 cause the deafness disorder DFNA9 in humans); and mammalian late gestation lung protein Lgl1, contains two tandem copies of the LCCL domain .
K Homology domain, type 2 (KH_dom_type_2)
Type: Domain

The K homology (KH) domain was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. It is a domain of around 70 amino acids that is present in a wide variety of quite diverse nucleic acid-binding proteins . It has been shown to bind RNA . Like many other RNA-binding motifs, KH motifs are found in one or multiple copies (14 copies in chicken vigilin) and, at least for hnRNP K (three copies) and FMR-1 (two copies), each motif is necessary for
in vitro
RNA binding activity, suggesting that they may function cooperatively or, in the case of single KH motif proteins (for example, Mer1p), independently .

According to structural analyses , the KH domain can be separated in two groups. The first group or type-1 contain a β-α-α-β-β-α structure, whereas in the type-2 the two last β-sheets are located in the N-terminal part of the domain (α-β-β-α-α-β). Sequence similarity between these two folds are limited to a short region (VIGXXGXXI) in the RNA binding motif. This motif is located between helice 1 and 2 in type-1 and between helice 2 and 3 in type-2. Proteins known to contain a type-2 KH domain include eukaryotic and prokaryotic S3 family of ribosomal proteins, and the prokaryotic GTP-binding protein era.
Glutathione S-transferase, N-terminal (Glutathione_S-Trfase_N)
Type: Domain

This entry represents the N-terminal domain of GST.

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of Cephalopoda is also a GST .

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family . GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulphur of GSH. These enzymes catalyse nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom .

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold, with each monomer composed of two distinct domains . The N-terminal domain forms a thioredoxin-like fold that binds the glutathione moiety, while the C-terminal domain contains several hydrophobic α-helices that specifically bind hydrophobic substrates.