SII-SWORD/CoKE huggingface dataset:
Ribonuclease III, endonuclease domain superfamily (RNase_III_sf)
Type: Homologous_superfamily

This domain superfamily is found in eukaryotic, bacterial and archeal ribonuclease III (RNAse III) proteins. RNAse III is a double stranded RNA-specific endonuclease . Prokaryotic RNAse III is important in post-transcriptional control of mRNA stability and translational efficiency. It is involved in the processing of ribosomal RNA precursors. Prokaryotic RNAse III also plays a role in the maturation of tRNA precursors and in the processing of phage and plasmid transcripts. Eukaryotic RNase III's participate (through direct cleavage) in rRNA processing, in processing of small nucleolar RNAs (snoRNAs) and snRNA's (components of the spliceosome). In eukaryotes RNase III or RNaseIII like enzymes such as Dicer are involved in RNAi (RNA interference) and miRNA (micro-RNA) gene silencing .

Bacterial RNase III proteins are the simplest members of the RNase III family, comprising an N-terminal nuclease domain fused to a C-terminal dsRNA binding domain (dsRBD) . The endonuclease domain structure has five helices where one of the helices is surrounded by the others.
Winged helix DNA-binding domain superfamily (WH_DNA-bd_sf)
Type: Homologous_superfamily

Winged helix DNA-binding proteins share a related winged helix-turn-helix DNA-binding motif, where the "wings", or loops, are small β-sheets. The winged helix motif consists of two wings (W1, W2), three α-helices (H1, H2, H3) and three β-sheets (S1, S2, S3) arranged in the order H1-S1-H2-H3-S2-W1-S3-W2 . The DNA-recognition helix makes sequence-specific DNA contacts with the major groove of DNA, while the wings make different DNA contacts, often with the minor groove or the backbone of DNA. Several winged-helix proteins display an exposed patch of hydrophobic residues thought to mediate protein-protein interactions.
Thionin-like superfamily (Thionin-like_sf)
Type: Homologous_superfamily

Thionins are small, basic plant proteins, 45 to 50 amino acids in length, which include three or four conserved disulphide linkages. The proteins are toxic to animal cells, presumably attacking the cell membrane and rendering it permeable: this results in the inhibition of sugar uptake and allows potassium and phosphate ions, proteins, and nucleotides to leak from cells . Thionins are mainly found in seeds where they may act as a defence against consumption by animals. A barley (Hordeum vulgare) leaf thionin that is highly toxic to plant pathogens and is involved in the mechanism of plant defence against microbial infections has also been identified . The hydrophobic protein crambin from the Abyssinian kale (Crambe abyssinica) is also a member of the thionin family .
PLAT/LH2 domain superfamily (PLAT/LH2_dom_sf)
Type: Homologous_superfamily

This entry represents a domain superfamily found in a variety of membrane or lipid associated proteins. It is known as the PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or LH2 (Lipoxygenase homology) domain, is found in a variety of membrane or lipid associated proteins. Structurally, this domain forms a β-sandwich composed of two sheets of four strands each . The most highly conserved regions coincide with the β-strands, with most of the highly conserved residues being buried within the protein. An exception to this is a surface lysine or arginine that occurs on the surface of the fifth β-strand of the eukaryotic domains. In pancreatic lipase, the lysine in this position forms a salt bridge with the procolipase protein. The conservation of a charged surface residue may indicate the location of a conserved ligand-binding site. It is thought that this domain may mediate membrane attachment via other protein binding partners.
Acetylglutamate kinase-like superfamily (AceGlu_kinase-like_sf)
Type: Homologous_superfamily

This entry contains proteins with various specificities and includes the acetylglutamate, aspartate, glutamate and uridylate kinase families. In prokaryotes and plants the synthesis of the essential amino acids lysine and threonine is predominantly regulated by feedback inhibition of aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS). In Escherichia coli, thrA, metLM, and lysC encode aspartokinase isozymes that show feedback inhibition by threonine, methionine, and lysine, respectively . The lysine-sensitive isoenzyme of aspartate kinase from spinach leaves has a subunit composition of 4 large and 4 small subunits .

In plants although the control of carbon fixation and nitrogen assimilation has been studied in detail, relatively little is known about the regulation of carbon and nitrogen flow into amino acids. The metabolic regulation of expression of an Arabidopsis thaliana aspartate kinase/homoserine dehydrogenase (AK/HSD) gene, which encodes two linked key enzymes in the biosynthetic pathway of aspartate family amino acids has been studied . The conversion of aspartate into either the storage amino acid asparagine or aspartate family amino acids may be subject to a coordinated, reciprocal metabolic control, and this biochemical branch point is a part of a larger, coordinated regulatory mechanism of nitrogen and carbon storage and utilization.
Ribosomal protein uL22 superfamily (Ribosomal_uL22_sf)
Type: Homologous_superfamily

Large ribosomal subunit protein uL22 (also known as L22 in bacteria and previously known as L17 in eukaryotes) is a core protein of the large ribosomal subunit . It is the only ribosomal protein that interacts with all six domains of 23S rRNA, and is one of the proteins important for directing the proper folding and stabilizing the conformation of 23S rRNA. uL22 is the largest protein contributor to the surface of the polypeptide exit channel, the tunnel through which the polypeptide product passes. uL22 is also one of six proteins located at the putative translocon binding site on the exterior surface of the ribosome .
Copper fist DNA-binding domain superfamily (Cu_fist_DNA-bd_dom_sf)
Type: Homologous_superfamily

Some fungal transcription factors contain an N-terminal domain, the copper fist, which seems to be involved in copper-dependent DNA-binding . These proteins activate the transcription of the metallothionein gene in response to copper. Metallothionein maintains copper levels in yeast . The copper fist domain, which is similar in structure to metallothionein itself, undergoes a large conformational change on copper-binding that allows DNA-binding. The domain contains a conserved array of zinc-binding residues (Cys-X2-Cys-X8-Cys-X-His) and forms a three-stranded antiparallel β-sheet with two short helical segments that project from one end of the β-sheet . Conserved residues form a basic patch that may be important for DNA binding.
Ribonuclease H superfamily (RNaseH_sf)
Type: Homologous_superfamily

The catalytic domain of several polynucleotidyl transferases share a similar structure, consisting of a 3-layer α/β/α fold that contains mixed β-sheets, suggesting that they share a similar mechanism of catalysis. Polynucleotidyl transferases containing this domain include ribonuclease H class I (RNase HI) and class II (RNase HII), HIV RNase (reverse transcriptase domain), retroviral integrase (catalytic domain), Mu transposase (core domain), transposase inhibitor Tn5 (containing additional all-α subdomains), DnaQ-like 3'-5' exonucleases (exonuclease domains), RuvC resolvase, and mitochondrial resolvase ydc2 (catalytic domain) .
Alpha carbonic anhydrase domain superfamily (CA_dom_sf)
Type: Homologous_superfamily

This entry represents a domain characteristic of alpha class carbonic anhydrases. The dominating secondary structure is a 10-stranded, twisted β-sheet, which divides the molecules into two halves . Alpha-CAs contain a single zinc atom bound to three conserved histidine residues. The catalytically active group is the zinc-bound water which ionizes to a hydroxide group. In the mechanism of catalysis, nucleophilic attack of CO2 by a zinc-bound hydroxide ion is followed by displacement of the resulting zinc-bound bicarbonate ion by water; subsequent deprotonation regenerates the nucleophilic zinc-bound hydroxide ion .

A carbonic anhydrase-like domain with striking homology to that of the alpha class carbonic anhydrases is also found in receptor-type tyrosine-protein phosphatase gamma and zeta. In this case it may have a different function, as only one of the three His residues that ligate the zinc atom and are required for catalytic activity is conserved .

Carbonic anhydrases (CA:

) are zinc metalloenzymes which catalyse the reversible hydration of carbon dioxide to bicarbonate . The alpha-CAs are found predominantly in animals but also in bacteria and green algae. There are at least 15 isoforms found in mammals, which can be subdivided into cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII), mitochondrial CAs (CA-VA and CA-VB), secreted CAs (CA-VI), membrane-associated (CA-IV, CA-IX, CA-XII and CA-XIV) and those without CA activity, the CA-related proteins (CA-RP VIII, X and XI).
Pesticidal crystal protein, central domain superfamily (Pest_cryst_cen_dom_sf)
Type: Homologous_superfamily

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production . When an insect ingests these proteins, they are activated by proteolytic cleavage. The N terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. The activated region of the toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (

) involved in membrane insertion and pore formation; a β-sheet central domain involved in receptor binding; and a C-terminal β-sandwich domain (

) that interacts with the N-terminal domain to form a channel .

This entry represents the central β-sheet domain superfamily, which consists of three four-stranded β-sheets, each with a Greek key fold, with internal pseudo threefold symmetry. Thus, it acts as a receptor binding β-prism, binding to insect-specific receptors of gut epithelial cells .
Cytochrome b5-like heme/steroid binding domain superfamily (Cyt_B5-like_heme/steroid_sf)
Type: Homologous_superfamily

Cytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases . There are two homologous forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of oxidoreductases consists of the juxtaposition of a heme-binding domain homologous to that of b5 and either a flavodehydrogenase or a molybdopterin domain. These enzymes are:

Lactate dehydrogenase (

) , an enzyme that consists of a flavodehydrogenase domain and a heme-binding domain called cytochrome b2.

Nitrate reductase ([ec:1.7.1.-]), a key enzyme involved in the first step of nitrate assimilation in plants, fungi and bacteria . Consists of a molybdopterin domain, a heme-binding domain called cytochrome b557, as well as a cytochrome reductase domain.

Sulfite oxidase (

) , which catalyzes the terminal reaction in the oxidative degradation of sulfur-containing amino acids. Also consists of a molybdopterin domain and a heme-binding domain.

Yeast acyl-CoA desaturase 1 (

; gene OLE1). This enzyme contains a C-terminal heme-binding domain.

Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.

Proteins containing a cytochrome b5-like domain also include:

Fission yeast hypothetical protein SpAC1F12.10c (C1F12.10c).

Yeast Irc21 (YMR073c), a putative protein with unknown function.
Small ribosomal subunit protein eS17 superfamily (Ribosomal_eS17_sf)
Type: Homologous_superfamily

These proteins have a DNA/RNA-binding 3-helical bundle fold, which consists of three helices with a close or partly open bundle and right-handed twist going up-and down.

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped in this family of ribosomal proteins, eS17 (RPS17) . They include, vertebrate, Drosophila and Neurospora crassa (crp-3) eS17's as well as yeast eS17a (RP51A) and eS17b (RP51B) and archaebacterial eS17 .
Elongation factor Ts, dimerisation domain superfamily (EF-Ts_dimer_sf)
Type: Homologous_superfamily

This superfamily describes a β(2)-α(n)-β two layers (α-β) fold domain of EF-Tu (EF1A). In E. coli and mitochondrial Ts there are two subdomains of this fold .

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .
Jacalin-like lectin domain superfamily (Jacalin-like_lectin_dom_sf)
Type: Homologous_superfamily

The jacalin-like mannose-binding lectin domain has a β-prism fold consisting of three 4-stranded β-sheets, with an internal pseudo 3-fold symmetry. Some proteins with this domain stimulate distinct T- and B- cell functions, such as the plant lectin jacalin, which binds to the T-antigen and acts as an agglutinin. The domain can occur in tandem-repeat arrangements with up to six copies, and in architectures combined with a variety of other functional domains. While the family was initially named after an abundant protein found in the jackfruit seed, taxonomic distribution is not restricted to plants. The domain is also found in the salt-stress induced protein from rice and an animal prostatic spermine-binding protein. Proteins containing this domain include:

Jacalin, a tetrameric plant seed lectin and agglutinin from Artocarpus heterophyllus (jackfruit), which is specific for galactose .

Artocarpin, a tetrameric plant seed lectin from A. heterophyllus .

Lectin MPA, a tetrameric plant seed lectin and agglutinin from Maclura pomifera (Osage orange), .

Heltuba lectin, a plant seed lectin and agglutinin from Helianthus tuberosus (Jerusalem artichoke) .

Agglutinin from Calystegia sepium (Hedge bindweed) .

Griffithsin, an anti-viral lectin from red algae (Griffithsia species) .
Oxygen-dependent coproporphyrinogen III oxidase superfamily (Coprogen_oxidase_aer_sf)
Type: Homologous_superfamily

Coprogen oxidase (i.e. coproporphyrin III oxidase or coproporphyrinogenase) catalyses the oxidative decarboxylation of coproporphyrinogen III to proto-porhyrinogen IX in the haem and chlorophyll biosynthetic pathways . The protein is a homodimer containing two internally bound iron atoms per molecule of native protein . The enzyme is active in the presence of molecular oxygen that acts as an electron acceptor. The enzyme is widely distributed having been found in a variety of eukaryotic and prokaryotic sources.

The coprogen oxidase has an α-β(6)-α(2)-β-α(n) structure. It is composed of three layers (α/β/α) with antiparallel sheets.
DM DNA-binding domain superfamily (DM_DNA-bd_sf)
Type: Homologous_superfamily

This entry represents the DM DNA-binding domain superfamily.

DMRT genes encode a conserved family of transcription factors that share a unique DNA binding motif, the DM domain . This domain was first discovered in the doublesex proteins of Drosophila melanogaster . In D. melanogaster the doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides . These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription . The DM domain binds DNA as a dimer, allowing the recognition of pseudopalindromic sequences . The NMR analysis of the DSX DM domain revealed a novel zinc module containing 'intertwined' CCHC and HCCC zinc-binding sites with an α-helical fold. The recognition of the DNA requires the carboxy-terminal basic tail which contacts the minor groove of the target sequence.
Photosystem I PsaA/PsaB superfamily (PSI_PsaA/B_sf)
Type: Homologous_superfamily

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. PSI is found in the chloroplast of plants and cyanobacteria. The electron transfer components of the reaction centre of PSI are a primary electron donor P-700 (chlorophyll dimer) and five electron acceptors: A0 (chlorophyll), A1 (a phylloquinone) and three 4Fe-4S iron-sulphur centres: Fx, Fa, and Fb.

PsaA and psaB, two closely related proteins, are involved in the binding of P700, A0, A1, and Fx. psaA and psaB are both integral membrane proteins of 730 to 750 amino acids that seem to contain 11 transmembrane segments. The Fx 4Fe-4S iron-sulphur centre is bound by four cysteines; two of these cysteines are provided by the psaA protein and the two others by psaB. The two cysteines in both proteins are proximal and located in a loop between the ninth and tenth transmembrane segments. A leucine zipper motif seems to be present downstream of the cysteines and could contribute to dimerisation of psaA/psaB.
Class II aldolase/adducin N-terminal domain superfamily (Aldolase_II/adducin_N_sf)
Type: Homologous_superfamily

This entry represents the α/β/α domain found in class II aldolases and in adducin (usually at the N terminus of adducin). Proteins containing this domain include: rhamnulose-1-phosphate aldolase (

), L-fuculose phosphate aldolase (

) that is involved in the third step in fucose metabolism, L-ribulose- 5-phosphate 4-epimerase (

) involved in the third step of L-arabinose catabolism, a probable sugar isomerase SgbE and the metazoan adducins, which have not been ascribed any enzymatic function but which play a role in cell membrane cytoskeleton organisation . It also includes ribulose-1-phosphate aldolase that catalyses the cleavage of ribulose 1-phosphate to dihydroxyacetone phosphate and glycolaldehyde .

This entry also includes the methylthioribulose-1-phosphate dehydratase of the methionine salvage pathway. This pathway allows methylthioadenosine, left over from polyamine biosynthesis, to be recycled to methionine.
Heat shock protein DnaJ, cysteine-rich domain superfamily (HSP_DnaJ_Cys-rich_dom_sf)
Type: Homologous_superfamily

This entry represents the central cysteine-rich (CR) domain of DnaJ proteins. This central cysteine rich domain (CR-type zinc finger) has an overall V-shaped extended β-hairpin topology and contains four repeats of the motif CXXCXGXG where X is any amino acid. The isolated cysteine rich domain folds in zinc dependent fashion. Each set of two repeats binds one unit of zinc. Although this domain has been implicated in substrate binding, no evidence of specific interaction between the isolated DnaJ cysteine rich domain and various hydrophobic peptides has been found .

The hsp70 chaperone machine performs many diverse roles in the cell, including folding of nascent proteins, translocation of polypeptides across organelle membranes, coordinating responses to stress, and targeting selected proteins for degradation. DnaJ is a member of the hsp40 family of molecular chaperones, which is also called the J-protein family, the members of which regulate the activity of hsp70s. DnaJ (hsp40) binds to DnaK (hsp70) and stimulates its ATPase activity, generating the ADP-bound state of DnaK, which interacts stably with the polypeptide substrate . Besides stimulating the ATPase activity of DnaK through its J-domain, DnaJ also associates with unfolded polypeptide chains and prevents their aggregation .

DnaJ consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acid residues, a glycine and phenylalanine-rich domain ('G/F' domain), a central cysteine rich domain (CR-type zinc finger) containing four repeats of a CXXCXGXG motif which can coordinate two zinc atom and a C-terminal domain (CTD) .
TorD-like superfamily (TorD-like_sf)
Type: Homologous_superfamily

This superfamily is represented by TorD. TorD is involved in the maturation of the the trimethylamine N-oxide reductase TorA (a DMSO reductase family member) in Escherichia coli . TorA is a molybdenum-containing enzyme which requires the the insertion of a bis(molybdopterin guanine dinucleotide) molybdenum (bis(MGD)Mo) cofactor in its catalytic site to be active and translocated to the periplasm. TorD acts as a chaperone, binding to apoTorA and promoting efficient incorporation of the cofactor into the protein.

This superfamily also includes DmsD, which could be required for the biogenesis of DMSO reductase rather than for the targeting of DmsA to the inner membrane . TorD and DmsD have a number of common features suggesting they function by using similar mechanisms. A major structural difference is that TorD is a domain-swapped dimer, while DmsD exists as a monomer .
HAD-like superfamily (HAD-like_sf)
Type: Homologous_superfamily

The large HAD-like superfamily of hydrolases comprises P-type ATPases, phosphatases, epoxide hydrolases and L-2-haloacid dehalogenases .

The haloacid dehydrogenase (HAD) superfamily includes phosphatases, phosphonatases, P-type ATPases, beta-phosphoglucomutases, phosphomannomutases, and dehalogenases, which are involved in a variety of cellular processes ranging from amino acid biosynthesis to detoxification .

Crystal structures of proteins from the HAD superfamily show that these proteins all share a conserved α/β-domain classified as a hydrolase fold, which is similar to the Rossmann fold . This conserved domain usually contains an insertion (sub)domain. For example, the crystal structure of a phosphoglycolate phosphatase from Thermoplasma acidophilum revealed two distinct domains, a larger core domain and a smaller cap domain. The large domain is composed of a centrally located five-stranded parallel β-sheet with strand order S10, S9, S8, S1, S2 and a small β-hairpin, strands S3 and S4. This central sheet is flanked by a set of three α-helices on one side and two helices on the other. The topology of the large domain is conserved; however, structural variation is observed in the smaller domain among the different functional classes of the haloacid dehalogenase superfamily.
YaeB-like superfamily (YaeB-like_sf)
Type: Homologous_superfamily

TrmO (also known as TsaA or YaeB) is a RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs. It has a unique single-sheeted β-barrel structure and represent a new category of AdoMet-dependent methyltransferases .
YaeB, N-terminal domain superfamily (YaeB_N_sf)
Type: Homologous_superfamily

TrmO (also known as TsaA or YaeB) is a RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs. It has a unique single-sheeted β-barrel structure and represent a new category of AdoMet-dependent methyltransferases .

The crystal structure of Haemophilus influenzae YaeB has been solved. In addition to the N-terminal β-barrel methyltransferase domain it has a C-terminal domain containing the conserved sequence motif DPRxxY . This superfamily describes the N-terminal domain.