SII-SWORD/CoKE huggingface dataset:
Hypoxia-inducible factor 1-alpha inhibitor, domain II (FIH-1_dom_II)
Type: Homologous_superfamily

This superfamily represents the domain II of the hypoxia-inducible factor 1-alpha inhibitor, which is composed of a central β-barrel surrounded by eight α-helices. It consists of two domains. Domain I runs from N terminus to residue 300 and is mainly composed of the central β-barrel and six α-helices surrounding them. Domain II (residues 301-349) comprising two consecutive α-helices stretches away from domain I. Domain II, which is completely missing in all known structures of the dioxygenase family, forms strong interactions with the same region of the 2-fold symmetry related molecule .
Histone-like protein H-NS, N-terminal (Histone_HNS_N)
Type: Homologous_superfamily

This superfamily represents N-terminal domain of histone-like H-NS proteins that is responsible for dimerisation and involved in transcriptional repression .
Spermine/spermidine acetyltransferase, N-terminal (Sper_AcTfrase_N)
Type: Homologous_superfamily

Spermine/spermidine acetyltransferase acetylates both spermidine and spermine at primary propyl amine moieties, with spermine being the preferred substrate .

This superfamily represents an helix-hairpin domain found at the N terminus of spermine/spermidine acetyltransferase.
Pheromone alpha factor receptor, double transmembrane domain superfamily (STE2_TM1-TM2_sf)
Type: Homologous_superfamily

Pheromone alpha factor receptor (STE2) is the receptor for the peptide pheromone alpha factor, which is a mating factor of yeast . Saccharomyces cerevisiae haploid cells secrete and respond to peptide mating factors; alpha cells secrete alpha factor, which induces cell-cycle arrest and expression of various genes in a cells, while a cells produce a factor, which has similar actions on alpha cells.

This superfamily represents a double transmembrane domain towards the N terminus of the alpha factor receptor. The ligand-binding site is probably in this domain .
Aerobic respiration control sensor protein ArcB, transmembrane domain superfamily (ArcB_TM_sf)
Type: Homologous_superfamily

Histidine kinase receptors (HKR) are part of a two-component system, in which an HKR in the bacterial inner membrane transmits a signal to a response regulator located in the cytoplasm.

Escherichia coli sensor kinase ArcB phosphorylates the partner response regulator ArcA in response to anaerobic conditions . ArcB is an atypical sensor kinase containing multiple phosphorylation domains: a histidine-containing phosphotransfer (HPt) signaling domain and a receiver domain in addition to the receptor and histidine-kinase (transmitter) domains, which are the two domains constituting a typical sensor kinase .

ArcB is a class 2 histidine kinase receptor (HKR). Class 2 HKRs lack an apparent extracytoplasmic domain and the stimuli-sensing region is believed to be in the membrane domain itself. ArcB has two transmembrane (TM) helices connected by a short periplasmic loop. This superfamily represents this transmembrane domain consisting of two helical motifs .
LD-carboxypeptidase A, C-terminal domain superfamily (Carboxypeptidase_A_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the LD-carboxypeptidase A. Muramoyl-tetrapeptide carboxypeptidase or LD-carboxypeptidase A hydrolyses a peptide bond between a di-basic amino acid and the C-terminal D-alanine in the tetrapeptide moiety in peptidoglycan. This cleaves the bond between an L- and a D-amino acid. The function of this activity is in murein recycling . Proteins containing this domain also include the microcin c7 self-immunity protein

and microcin immunity protein MccF .
Z ring-associated protein D, C-terminal (ZapD_C)
Type: Homologous_superfamily

This superfamily represents a β sandwich domain found at the C terminus of Z ring-associated protein D (ZapD) and in other proteins currently uncharacterised. ZapD enhances FtsZ-ring assembly .
Multidrug efflux transporter AcrB TolC docking domain, DN/DC subdomains (AcrB_DN_DC_subdom)
Type: Homologous_superfamily

The multidrug exporter AcrB is the inner membrane component of the AcrAB-TolC drug efflux system in Escherichia coli, responsible for the resistance of this organism to a wide range of drugs. AcrB exists as a homotrimer, with each subunit containing 12 transmembrane (TM) helices and a large periplasmic part formed by two loops between TM helices 1 and 2 and TM helices 7 and 8. The trimer consists of three prominent domains, the TM domain, the adjacent pore domain and the TolC docking domain .
Ornithine decarboxylase, N-terminal (Ornithine_deCO2ase_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of the ornithine decarboxylase (

), which is involved in putrescine biosynthesis.
Proteinase inhibitor I35b (TIMP), C-terminal (TIMP_C)
Type: Homologous_superfamily

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs). TIMPs have two domains, a larger N-terminal domain that carries the MMP-inhibitory activity, and a smaller C-domain that mediates other interactions, notably non-inhibitory interactions of TIMP-1 with pro-MMP-9 and of TIMP-2 with pro-MMP-2 .

This superfamily represents the C-terminal domain.
Molybdopterin oxidoreductase, molybdopterin cofactor binding site (MopterinOxRdtase_cofactor_BS)
Type: Binding_site

The molybdopterin oxidoreductase 4Fe-4S domain is found in a number of reductase/dehydrogenase families, which include the periplasmic nitrate reductase precursor and the formate dehydrogenase alpha chain . This entry represents the molybdopterin cofactor binding site within the domain.
Alpha-dystroglycan domain 2 (Alpha-dystroglycan_domain_2)
Type: Homologous_superfamily

Alpha-dystroglycan is a subunit of the dystroglycan complex. It is an extracellular peripheral glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains, and for certain adenoviruses . The N terminus of alpha-dystroglycan comprises of domain 1 with an immunoglobulin-like β-sandwich fold and domain 2 that resembles ribosomal RNA-binding proteins . It has been suggested that alpha-dystroglycan has a central mucin-like domain followed by another immunoglobulin-like β-sandwich domain . This entry represents domain 2.
Cation efflux transmembrane domain superfamily (Cation_efflux_TMD_sf)
Type: Homologous_superfamily

The cation diffusion facilitator family (CDF) have members in both prokaryotes and eukaryotes, several of which have been shown to transport cobalt, cadmium and/or zinc. CDF transporters share a common two-modular architecture, consisting of a transmembrane domain (TMD) followed by a C-terminal domain (CTD) protruding into the cytoplasm .

This superfamily represents the CDF N-terminal transmembrane domain.
Cation efflux protein, cytoplasmic domain (Cation_efflux_CTD)
Type: Domain

The cation diffusion facilitator family (CDF) have members in both prokaryotes and eukaryotes, several of which have been shown to transport cobalt, cadmium and/or zinc. CDF transporters share a common two-modular architecture, consisting of a transmembrane domain (TMD) followed by a C-terminal domain (CTD) protruding into the cytoplasm .

This entry represents the CDF C-terminal cytoplasmic domain. The cytoplasmic domain of Zinc transporter YiiP adopts a metallochaperone-like fold. The use of this common structural module to regulate metal coordination chemistry may enable a tunable transport activity in response to cytoplasmic metal fluctuations . It is the dimerisation region of the whole molecule of zinc transporters since the full-length members form a homodimer during activity. The domain lies within the cytoplasm and exhibits an overall structural similarity with the copper metallochaperone Hah1 (

) exhibiting an open α-β domain with two α helices (H1 and H2) aligned on one side and a three-stranded mixed β-sheet (S1 to S3) on the other side .
YbeD-like domain superfamily (YbeD-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in several uncharacterised proteins, including YbeD from Escherichia coli. YbeD shows structural homology to the regulatory domain from 3-phosphoglycerate dehydrogenase, suggesting a role in the allosteric regulation of lipoic acid biosynthesis or the glycine cleavage system .
Pput2613-like deaminase (Pput2613-NH3ase)
Type: Family

This family is represented by a member of the nucleic acid/nucleotide deaminase superfamily found in Pseudomonas Pput_2613 . Members of this family are predicted to function as toxins in bacterial polymorphic toxin systems .
L-asparaginase, C-terminal (L-asparaginase_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the L-asparaginase. Each monomer of L-asparaginase is arranged into two easily identifiable domains, the larger N-terminal domain and the smaller C-terminal domain, connected by a linker consisting of approximately 20 residues . Asparaginase is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma . This domain is also found in the related enzymes L-glutaminase-asparaginase from bacteria (

) , archaeal GatD subunit of Glu-tRNA amidotransferase (Glu-AdT) and mammalian lysophospholipase (

), which is believed to play a major role in the hydrolytic degradation of lysophosphatidylcholine .
L-asparaginase, N-terminal (L-asparaginase_N)
Type: Domain

This entry represents the N-terminal domain of the L-asparaginase. Each monomer of L-asparaginase is arranged into two easily identifiable domains, the larger N-terminal domain and the smaller C-terminal domain, connected by a linker consisting of approximately 20 residues . The N-terminal domain covers two conserved threonine residues, which have been shown to play a catalytic role . One of them is located in the N-terminal extremity while the second one is located at the end of the first third of the sequence.

Asparaginase is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma . Glutaminase, a similar enzyme, catalyses the deaminination of glutamine to glutamic acid and an ammonium ion . Both asparaginase and glutaminase contain the domain represented in this entry.
Asparaginase/glutaminase, active site 2 (Asparaginase/glutaminase_AS2)
Type: Active_site

Asparaginase, which is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma . The enzyme is effective in the treatment of human malignant lymphomas, which have a diminished capacity to produce asparagine synthetase: in order to survive, such cells absorb asparagine from blood plasma - if Asn levels have been depleted by injection of asparaginase, the lymphoma cells die. Glutaminase, a similar enzyme, catalyses the deaminination of glutamine to glutamic acid and an ammonium ion . Both enzymes are homotetramers : two threonine residues in the N-terminal half of the proteins are involved in the catalytic activity.

Two conserved threonine residues have been shown to play a catalytic role . One of them is located in the N-terminal extremity while the second is located at the end of the first third of the sequence. This entry represents the second conserved site.
D-aminopeptidase, N-terminal (DppA_N)
Type: Homologous_superfamily

This entry represents the N-terminal domain of D-aminopeptidase. The motif SXDXEG, located near the N terminus (residues 6-11 in DppA) is conserved in all but one of these known DppA homologues (in Clostridium difficile the sequence is SXDXEV) . DppA is a self-compartmentalising protease, a family of proteolytic complexes. Proteasomes are the most extensively studied representatives of this family. The DppA enzyme is composed of identical 30kDa subunits organised in a decamer with 52 point-group symmetry. A 20 A wide channel runs through the complex, giving access to a central chamber holding the active sites. The only known substrates are D-ala-D-ala and D-ala-gly-gly.
Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain superfamily (Succ_DH/fumarate_Rdtase_cat_sf)
Type: Homologous_superfamily

Succinate:quinone oxidoreductase (

) refers collectively to succinate:quinone reductase (SQR, or Complex II) and quinol:fumarate reductase (QFR) . SQR is found in aerobic organisms, and catalyses the oxidation of succinate to fumarate in the citric acid cycle and donates the electrons to quinone in the membrane. QFR can be found in anaerobic cells respiring with fumarate as terminal electron acceptor. SQR and QFR are very similar in composition and structure, despite catalysing opposite reactions
in vivo
. They are thought to have evolved from a common ancestor, and in Escherichia coli they are capable of functionally replacing each other .

Succinate:quinone oxidoreductases consist of a peripheral domain, exposed to the cytoplasm in bacteria and to the matrix in mitochondria, and a membrane-integral anchor domain that spans the membrane. The peripheral part, which contains the dicarboxylate binding site, is composed of a flavoprotein subunit, with one covalently bound FAD, and an iron-sulphur protein subunit containing three iron-sulphur clusters. The membrane-integral domain functions to anchor the peripheral domain to the membrane and is required for quinone reduction and oxidation. The anchor domain shows the largest variability in composition and primary sequence, being composed either of one large subunit, or two smaller subunits, which may, or may not, contain protoheme groups.

The flavoprotein subunit found in both the SQR and QFR enzymes contains an N-terminal domain which binds the FAD cofactor, a central catalytic domain with an unsual fold, and a C-terminal domain whose role is unclear . The dicarboxylate binding site is located between the FAD and catalytic domains.

This superfamily represents the catalytic domain of the flavoprotein subunit.
Murein tetrapeptide carboxypeptidase, N-terminal (LdcA_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal of muramoyl-tetrapeptide carboxypeptidase, also known as LD-carboxypeptidase A. The enzyme hydrolyses a peptide bond between a di-basic amino acid and the C-terminal D-alanine in the tetrapeptide moiety in peptidoglycan. This cleaves the bond between an L- and a D-amino acid. This activity is has a role ine in murein recycling . Proteins containing this domain also include the microcin c7 self-immunity protein

.
S-Me-THD, N-terminal domain superfamily (S-Me-THD_N_sf)
Type: Homologous_superfamily

This 3-layer(aba) sandwich domain is found at the N terminus of S-methyl thiohydantoin desulfurase from Variovorax sp. (S-Me-THD) and similar sequences mainly found in bacteria and fungi. S-Me-THD catalyses the hydrolysis of S-methyl-thiohydantoin-5-propanoate into hydantoin-5-propanoate and methanethiol, the third step in S-methyl ergothioneine degradation .
HIV-1 Nef protein, anchor domain superfamily (HIV-1_Nef_anchor_sf)
Type: Homologous_superfamily

Human immunodeficiency virus 1 (HIV-1) negative factor (Nef protein) accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases .

Negative factor (Nef) has a two-domain structure consisting of an N-terminal anchor domain and a core domain separated by a specific cleavage site of the HIV proteases. The N-terminal domain is not compactly folded and constitutes a mobile membrane anchor and a linker to the core domain .
HIV-1 Nef protein, core domain superfamily (HIV-1_Nef_core_sf)
Type: Homologous_superfamily

Human immunodeficiency virus 1 (HIV-1) negative factor (Nef protein) accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases .

Negative factor (Nef) has a two-domain structure consisting of an N-terminal anchor domain and a core domain separated by a specific cleavage site of the HIV proteases. The N-terminal domain is not compactly folded and constitutes a mobile membrane anchor and a linker to the core domain .
Sec1-like, domain 2 (Sec1-like_dom2)
Type: Homologous_superfamily

This entry represents domain 2 from the Sec1 family which includes Sec1, Sly1, Slp1/Vps33, yeast Vps45/Stt10, Unc-18 from nematodes, Munc-18b/muSec1, Munc-18c from mouse, Rop from Drosophila, Munc-18/n-Sec1/rbSec1A and rbSec1B from rat .

Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis . They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion .

The nSec1 polypeptide chain can be divided into three domains. The first domain, consists of a five-stranded parallel β-sheet flanked by five α-helices. The second domain, like the first one, has an α-β-α fold, however the β-sheet of domain 2 features five parallel strands with an additional antiparallel strand on one edge. The third domain is a large insertion between the third and fourth parallel strands of domain 2, and can be subdivided in two .
Phosphatidylinositol-4-phosphate 4/5-kinase, C-terminal domain superfamily (PInositol-4-P-4/5-kinase_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the phosphatidylinositol-4-phosphate 4/5-kinases (PIP4K/PIP5K). It has a 2-layer sandwich structure . PIP4/5K catalyses the formation of phosphoinositol-4,5-bisphosphate via the phosphorylation of phosphatidylinositol-4-phosphate a precursor in the phosphoinositide signalling pathway .
Phosphatidylinositol-4-phosphate 5-kinase, N-terminal (PInositol-4-P-5-kinase_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of the phosphatidylinositol-4-phosphate 5-kinase (PIP5K). It has a 2-layer sandwich structure . PIP5K catalyses the formation of phosphoinositol-4,5-bisphosphate via the phosphorylation of phosphatidylinositol-4-phosphate, a precursor in the phosphinositide signalling pathway .
AMMECR1, N-terminal (AMMECR1_N)
Type: Homologous_superfamily

This entry represents an N-terminal subdomain of the AMMECR1 domain (

). It consists of a 2-layer sandwich structure. Defects in Nuclear protein AMMECR1 (AMMECR1) are involved association of Alport syndrome, midface hypoplasia, intellectual disability and elliptocytosis in humans .
Small ribosomal subunit protein uS10 domain (Ribosomal_uS10_dom)
Type: Domain

This entry represents the structural domain of the small ribosomal subunit protein uS10, which has a ferredoxin-like fold.

Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA . The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.

The small ribosomal subunit protein uS10 consists of about 100 amino acid residues. In Escherichia coli, uS10 is involved in binding tRNA to the ribosome, and also operates as a transcriptional elongation factor . Experimental evidence has revealed that uS10 has virtually no groups exposed on the ribosomal surface, and is one of the "split proteins": these are a discrete group that are selectively removed from 30S subunits under low salt conditions and are required for the formation of activated 30S reconstitution intermediate (RI*) particles. uS10 belongs to a family of proteins that includes: bacteria uS10; algal chloroplast uS10c; cyanelle uS10; archaebacterial uS10; Marchantia polymorpha and Prototheca wickerhamii mitochondrial S10; Arabidopsis thaliana mitochondrial uS10m (nuclear encoded); vertebrate uS10 (also known as S20); plant u S10 (also known as S20); and yeast uS10 (URP2).
Large ribosomal subunit protein mL48 (Ribosomal_mL48)
Type: Family

This entry represents the large ribosomal subunit protein mL48, also known as mitochondrial ribosomal protein L48. It interacts with Oxa1L, a mitochondrial inner membrane protein that facilitates the insertion of both mitochondrial- and nuclear-encoded proteins from the mitochondrial matrix into the inner membrane .
Small ribosomal subunit protein uS3, archaeal (Ribosomal_uS3_arc)
Type: Family

This family describes the small ribosomal subunit protein uS3, also known as ribosomal protein S3, from archaea.

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 .