SII-SWORD/CoKE huggingface dataset:
Ribosomal protein bL12, C-terminal/adaptor protein ClpS-like (Ribosomal_bL12_C/ClpS-like)
Type: Homologous_superfamily

This superfamily represents a domain found at the C terminus of ribosomal proteins bL12, and also in the adaptor protein ClpS, forming an α/β sandwich .

The bL12 ribosomal proteins are part of the large 50S ribosomal subunit, and occur in four copies organised as two dimers. The bL12 dimer probably interacts with EF-Tu .

ClpS is an adaptor protein that influences protein degradation through its binding to the N-terminal domain of the chaperone ClpA in the ClpAP chaperone-protease pair. The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS. ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated 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 .
Double-stranded RNA-binding domain (dsRBD_dom)
Type: Domain

In contrast to other RNA-binding domains, the about 65 amino acids long dsRBD domain has been found in several proteins that specifically recognise double-stranded RNAs. The dsRBD domain is also known as DSRM (Double-Stranded RNA-binding Motif). dsRBD proteins are mainly involved in posttranscriptional gene regulation, for example, by preventing the expression of proteins or by mediating RNAs localisation. This domain is also found in RNA editing proteins. Interaction of the dsRBD with RNA is unlikely to involve the recognition of specific sequences . Nevertheless, multiple dsRBDs may be able to act in combination to recognise the secondary structure of specific RNAs (i.e. Staufen) . NMR analysis of the third dsRBD of Drosophila Staufen has revealed an α-β-β-β-α structure . This domain is found in Ribonuclease 3 and related proteins.
Small ribosomal subunit protein uS5 domain 2-type fold, subgroup (Ribsml_uS5_D2-typ_fold_subgr)
Type: Homologous_superfamily

Domain 2 of the small ribosomal subunit protein uS5, previously known as ribosomal protein S5, has a left-handed β-α-β fold that is found in numerous RNA/DNA-binding proteins, as well as in kinases from the GHMP kinase family. Proteins containing this β-α-β fold domain include:

Translational machinery components (ribosomal proteins S5 and S9, and domain IV of elongation factors EF-G and eEF-2) .

Ribonuclease P protein (RNase P) .

DNA modification proteins (DNA mismatch repair proteins MutL and PMS2, DNA gyrase B, DNA topoisomerase II, IV-B and VI-B) .

GHMP kinases that transfer a phosphoryl group from ATP to an acceptor (galactokinase (

), homoserine kinase (

), and mevalonate kinase (

)) .

Caenorhabditis elegans early switch protein Xol-1 (a divergent member of the GHMP kinase family that has lost the ATP-binding site) .
Large ribosomal subunit protein uL2, domain 2 (Rib_uL2_dom2)
Type: Homologous_superfamily

This domain superfamily can be found in the large ribosomal subunit protein uL2, previously known as ribosomal protein L2, where it represents domain 2 and it is also found in other ribosomal proteins and in elongation factor P and translation initiation factor 5A, where it constitutes the N-terminal domain .
RNA polymerase Rpb2, OB-fold (RNA_pol_RPB2_OB-fold)
Type: Homologous_superfamily

RNA polymerases (

) catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This entry describes a structural region consisting of an OB-fold β barrel that is found in RNA polymerase II Rpb2 .
Large ribosomal subunit protein uL2, domain 3 (Ribosomal_uL2_dom3)
Type: Homologous_superfamily

This superfamily represents domain 3 of the ribosomal protein uL2 from the large 50S subunit. The 50S subunit proteins function primarily to stabilise inter-domain interactions that are necessary to maintain the subunit's structural integrity, displaying a wide variety of protein-RNA interactions. This domain has an irregular structure .

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 .
DNA topoisomerase I, catalytic core, alpha/beta subdomain (TopoI_cat_a/b-sub_euk)
Type: Homologous_superfamily

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

This entry represents the α/β subdomain that comprises part of the catalytic core of eukaryotic and viral topoisomerase I (type IB) enzymes, which occurs near the C-terminal region of the protein.
Rossmann-like alpha/beta/alpha sandwich fold (Rossmann-like_a/b/a_fold)
Type: Homologous_superfamily

This superfamily represents domains related by a common ancestor that have a Rossmann-like, 3-layer, α/β/α sandwich fold. Protein families in which the domain is found include:

Nucleotidylyl transferases (

) such as cytidylyltransferases , adenylyltransferases .

Class I aminoacyl-tRNA synthetases (catalytic domain), such as tyrosyl-tRNA synthetase (

) and glutaminyl-tRNA synthetase (

) .

Pantothenate synthetases (

) .

ATP sulphurylase (central domain)

N-type ATP pyrophosphatases, such as beta-lactam synthetase (

) and GMP synthase (

) .

PP-loop ATPases such as the cell cycle protein MesJ (N-terminal domain) .

Phosphoadenylyl sulphate (PAPS) reductase

Electron transfer flavoprotein (ETFP) subunits, such as the N-terminal domains of the alpha and beta subunits .

Universal stress protein A (UspA) .

Cryptochrome and DNA photolyase .
Electron transfer flavoprotein, alpha/beta-subunit, N-terminal (ETF_a/b_N)
Type: Domain

This entry represents the N-terminal domain of both the alpha and beta subunits from Group I and Group II ETFs.

Electron transfer flavoproteins (ETFs) serve as specific electron acceptors for primary dehydrogenases, transferring the electrons to terminal respiratory systems. They can be functionally classified into constitutive, "housekeeping" ETFs, mainly involved in the oxidation of fatty acids (Group I), and ETFs produced by some prokaryotes under specific growth conditions, receiving electrons only from the oxidation of specific substrates (Group II) .

ETFs are heterodimeric proteins composed of an alpha and beta subunit, and contain an FAD cofactor and AMP . ETF consists of three domains: domains I and II are formed by the N- and C-terminal portions of the alpha subunit, respectively, while domain III is formed by the beta subunit. Domains I and III share an almost identical α-β-α sandwich fold, while domain II forms an α-β-α sandwich similar to that of bacterial flavodoxins. FAD is bound in a cleft between domains II and III, while domain III binds the AMP molecule. Interactions between domains I and III stabilise the protein, forming a shallow bowl where domain II resides.
Electron transfer flavoprotein, alpha subunit, C-terminal (ETF_asu_C)
Type: Domain

Electron transfer flavoproteins (ETFs) serve as specific electron acceptors for primary dehydrogenases, transferring the electrons to terminal respiratory systems. They can be functionally classified into constitutive, "housekeeping" ETFs, mainly involved in the oxidation of fatty acids (Group I), and ETFs produced by some prokaryotes under specific growth conditions, receiving electrons only from the oxidation of specific substrates (Group II) .

ETFs are heterodimeric proteins composed of an alpha and beta subunit, and contain an FAD cofactor and AMP . ETF consists of three domains: domains I and II are formed by the N- and C-terminal portions of the alpha subunit, respectively, while domain III is formed by the beta subunit. Domains I and III share an almost identical α-β-α sandwich fold, while domain II forms an α-β-α sandwich similar to that of bacterial flavodoxins. FAD is bound in a cleft between domains II and III, while domain III binds the AMP molecule. Interactions between domains I and III stabilise the protein, forming a shallow bowl where domain II resides.

This entry represents the C-terminal domain of the alpha subunit of both Group I and Group II ETFs.
Orotidine 5'-phosphate decarboxylase (OMPdecase)
Type: Family

Orotidine 5'-phosphate decarboxylase (OMPdecase) (

) catalyses the last step in the
de novo
biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional proteins.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centred around a lysine residue which is essential for the catalytic function of the enzyme.

OMPdecases adopt classical TIM-barrel fold with an active site located at one side of the barrel .
Transposase, Tn5-like, N-terminal (Transposase_Tn5-like_N)
Type: Domain

This domain is found at the N-terminal of Tn5-type transposase proteins. Prokaryotic Tn5 transposase makes two types of DNA contacts (cis-contacts for DNA recognition and trans-contacts for catalysis) as well as protein-protein contacts . Tn5 transposase employs two cations at its active site during catalysis, which cause conformational changes in the bound DNA and which are required for transposition . Tn5 transposase has a RnaseH-type α/β/α fold. The N-terminal domain forms an orthogonal α-bundle structure.
Transposase, Tn5-like, C-terminal (Transposase_Tn5-like_C)
Type: Homologous_superfamily

This superfamily represents a domain found at the C-terminal of Tn5-type transposase proteins. Prokaryotic Tn5 transposase makes two types of DNA contacts (cis-contacts for DNA recognition and trans-contacts for catalysis) as well as protein-protein contacts . Tn5 transposase employs two cations at its active site during catalysis, which cause conformational changes in the bound DNA and which are required for transposition . Tn5 transposase has a RnaseH-type α/β/α fold. The C-terminal domain forms an orthogonal α-bundle structure.
Citrate transporter (Citrate_transporter)
Type: Family

This entry consists of known and predicted citrate transporters. It includes two characterised citrate/proton symporters, CitM and CitH, from Bacillus subtilis . Both of these proteins couple the uptake of citrate in complex with a divalent cation to the uptake of protons, but differ in their metal ion specificities. CitM transports citrate in complex with Mg2, Ni2, Mn2, Co2, and Zn2, while CitH transports citrate in complex with Ca2, Ba2, and Sr2. A third paralog, YraO, exists in B. subtilis, but the function of this protein is not known. Other characterised systems for metal-citrate transport in this family are those of Streptococcus mutans and Enterococcus faecalis .
Channel forming colicin, N-terminal domain superfamily (Channel_colicin_N_sf)
Type: Homologous_superfamily

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 colicin, central receptor recognition (Channel_colicin_cen)
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 central receptor recognition domain, which has an α/β two-layer sandwich structure.
Adaptor protein Cbl, EF hand-like (Adaptor_Cbl_EF_hand-like)
Type: Domain

Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface.

The N-terminal region of Cbl contains a Cbl-type phosphotyrosine-binding (Cbl-PTB) domain, which is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle (4H) domain, an EF hand-like calcium-binding domain, and a divergent SH2-like domain. The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The Cbl-PTB domain has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain .

The N-terminal 4H domain contains four long α-helices. The C and D helices in this domain pack against the adjacent EF-hand-like domain, and a highly conserved loop connecting the A and B helices contacts the SH2-like domain. The EF-hand motif is similar to classical EF-hand proteins. The SH2-like domain retains the general helix-sheet-helix architecture of the SH2 fold, but lacks the secondary β-sheet, comprising β-strands D', E and F, and also a prominent BG loop .

This entry represents the EF hand-like domain.
Adaptor protein Cbl, SH2-like domain (Adaptor_Cbl_SH2-like)
Type: Domain

Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface.

The N-terminal region of Cbl contains a Cbl-type phosphotyrosine-binding (Cbl-PTB) domain, which is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle (4H) domain, an EF hand-like calcium-binding domain, and a divergent SH2-like domain. The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The Cbl-PTB domain has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain .

The N-terminal 4H domain contains four long α-helices. The C and D helices in this domain pack against the adjacent EF-hand-like domain, and a highly conserved loop connecting the A and B helices contacts the SH2-like domain. The EF-hand motif is similar to classical EF-hand proteins. The SH2-like domain retains the general helix-sheet-helix architecture of the SH2 fold, but lacks the secondary β-sheet, comprising β-strands D', E and F, and also a prominent BG loop .

This entry represents the SH2-like domain.
Chloride channel, core (Cl-channel_core)
Type: Homologous_superfamily

Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport . Some members are plasma membrane Cl channels, while others are Cl/H exchangers .

The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata , and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl-channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl-channels is that some of the isoforms may function as Cl-channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains . Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N-and C-termini residing in the cytoplasm .

A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl-channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia . Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl-channel, lead to several forms of inherited kidney stone disease . These mutations have been demonstrated to reduce or abolish CLC function.

This superfamily represents the core domain of the cholide ion channel.
Nuclear receptor coactivator, CREB-bp-like, interlocking (Nuc_rcpt_coact_CREBbp)
Type: Domain

This entry represents the interlocking domain of the eukaryotic nuclear receptor coactivators CREBP and p300. The interlocking domain forms a 3-helical non-globular array that forms interlocked heterodimers with its target.

Nuclear receptors are ligand-activated transcription factors involved in the regulation of many processes, including development, reproduction and homeostasis. Nuclear receptor coactivators act to modulate the function of nuclear receptors. Coactivators associate with promoters and enhancers primarily through protein-protein contacts to facilitate the interaction between DNA-bound transcription factors and the transcription machinery. Many of these coactivators are structurally related, including CBP (CREB-binding protein) and p300 . CBP and p300 both have histone acetyltransferase activity (

). CBP/p300 proteins function synergistically to activate transcription, acting to remodel chromatin and to recruit RNA polymerase II and the basal transcription machinery. CBP is required for proper cell cycle control, differentiation and apoptosis. The interaction of CBP/p300 with transcription factors involves several small domains. The IBiD domain in the C-terminal of CBP is responsible for CBP interaction with IRF-3, as well as with the adenoviral oncoprotein E1A, TIF-2 coactivator, and the IRF homologue KSHV IRF-1 .