SII-SWORD/CoKE huggingface dataset:
CobE/GbiG C-terminal domain superfamily (CobE/GbiG_C_sf)
Type: Homologous_superfamily

Cobalt-precorrin-5A hydrolase CbiG is specific for anaerobic cobalamin (vitamin B12) biosynthesis. CbiG, which shows homology with CobE of the aerobic pathway, participates in the conversion of cobalt-precorrin 5 into cobalt-precorrin 6 . CbiG is responsible for the opening of the delta-lactone ring and extrusion of the C2-unit . The aerobic pathway uses molecular oxygen to trigger the events at C-20 leading to contraction and expulsion of the C2-unit as acetic acid from a metal-free intermediate, whereas the anaerobic route involves the internal delivery of oxygen from a carboxylic acid terminus to C-20 followed by extrusion of the C2-unit as acetaldehyde, using cobalt complexes as substrates .

This entry represents a domain superfamily found at the C terminus of CibG. CobE is composed solely of this domain. The structure of this domain has three layers (α/β/α) with a mixed β-sheet of five strands, where the strand 5 is antiparallel to the rest.
Uncharacterised UPF0058 superfamily (UPF0058_sf)
Type: Homologous_superfamily

These archaebacterial proteins have no known function. Members of the family are about 90-105 amino acid residues long.
UPF0759 superfamily (UPF0759_sf)
Type: Homologous_superfamily

The function of these proteins is unknown. Aquifex aeolicus has two copies of this protein. A probable aspartyl-tRNA synthetase from Escherichia coli belongs to this group.
Signal recognition particle, subunit SRP19-like superfamily (SRP19-like_sf)
Type: Homologous_superfamily

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the SRP19 subunit. The SRP19 protein is unstructured but forms a compact core domain and two extended RNA-binding loops upon binding the signal recognition particle (SRP) RNA .
Molybdopterin cofactor biosynthesis C (MoaC) domain superfamily (MoaC_sf)
Type: Homologous_superfamily

The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism .

This entry represents the molybdenum cofactor biosynthesis protein MoaC from prokaryotes and eukaryotes, also known as cyclic pyranopterin monophosphate synthase.

The MoaC structure has a Ferredoxin-like fold, which consists of an α+β sandwich with antiparallel β-sheet.
SurE-like phosphatase/nucleotidase superfamily (SurE-like_sf)
Type: Homologous_superfamily

This entry represents a SurE-like structural domain superfamily with a 3-layer α/β/α topology that bears some topological similarity to the N-terminal domain of the glutaminase/asparaginase family. This domain is found in the stationary phase survival protein SurE, a metal ion-dependent phosphatase found in eubacteria, archaea and eukaryotes. In Escherichia coli, SurE also has activity as a nucleotidase and exopolyphosphatase, and may be involved in the stress response . E. coli cells with mutations in the surE gene survive poorly in stationary phase . The structure of SurE homologues have been determined from Thermotoga maritima and the archaea Pyrobaculum aerophilum . The T. maritima SurE homologue has phosphatase activity that is inhibited by vanadate or tungstate, both of which bind adjacent to the divalent metal ion.
Frataxin/CyaY superfamily (Frataxin/CyaY_sf)
Type: Homologous_superfamily

The eukaryotic proteins in this entry include Frataxin, the protein that is mutated in Friedreich's ataxia , and related sequences. Friedreich's ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the gene encoding Frataxin (FRDA). Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human Frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat) .

The bacterial proteins in this entry are iron-sulphur cluster (FeS) metabolism CyaY proteins homologous to eukaryotic Frataxin. Partial Phylogenetic Profiling suggests that CyaY most likely functions as part of the ISC system for FeS cluster biosynthesis, and is supported by experimental data in some species .

The structure of Frataxin/CyaY has an α-β(5)-α fold arranged in two layers (α/β) with meander antiparallel sheet.
Tubulin/FtsZ, GTPase domain superfamily (Tubulin/FtsZ_GTPase_sf)
Type: Homologous_superfamily

This entry represents a GTPase domain found in all tubulin chains, such as tubulin alpha, beta and gamma chains, plant ARC3 and prokaryotic FtsZ and CetZ proteins . These proteins are involved in polymer formation. Tubulin is the major component of microtubules, while FtsZ (homologue of eukaryotic tubulin) is the polymer-forming protein of bacterial cell division, it is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells . FtsZ can polymerise into tubes, sheets, and rings in vitro and is ubiquitous in bacteria and archaea. CetZ co-exists with FtsZ in many archaea. Cetz does not affect cell division, instead, it is involved in cell shape control . Arabidopsis chloroplast protein ARC3 (At1g75010) is a Z-ring accessory protein involved in the initiation of plastid division and division site placement .

The structure of the GTPase domain has a three layers (α/β/α) with a parallel β-sheet of six strands.
Carbon-nitrogen hydrolase superfamily (C-N_Hydrolase_sf)
Type: Homologous_superfamily

The carbon-nitrogen hydrolase domain is an around 265-residue domain found in numerous enzymes involved in the reduction of organic nitrogen compounds and ammonia production. Based on their sequence similarity and on the reactions
they catalyse, these enzymes can be classified into functionally distinct groups including :

Nitrilases (

), which cleave various nitriles into the corresponding acids and ammonia.

Cyanide hydratase (

) of pathogenic fungi, which detoxifies HCN that is released by their hosts, cyanogenic plants, after injury.

Aliphatic amidases (

), which enable prokaryotes to use acetamides as both carbon and nitrogen source.

Beta-ureidopropionase (also known as beta-alanine synthase or N-carbamoyl-beta-alanine amino hydrolase;

), which catalyses the last step of pyrimidine catabolism.

Glutamine-dependent NAD(+) synthetase (also known as AdgA, for ammonia-dependent growth) from Rhodobacter species (

). It appears to be essential for using various amino acids as nitrogen sources.

Biotinidase (

), which catalyses the hydrolysis of biocytin to biotin and lysine.

Pantetheinase (

) (Pantetheine hydrolase) (Vanin), which hydrolyzes specifically one of the carboamide linkages in D-pantetheine, thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.

Apolipoprotein N-acyltransferase ([ec:2.3.1.-]) (gene lnt), a bacterial enzyme that transfers the fatty acyl group on membrane lipoproteins.

Glutamine-dependent NAD(+) synthetase (

), which catalyses the final step in NAD+ synthesis .

The carbon-nitrogen hydrolase domain is characterised by several conserved motifs, one of which contains a cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes a glutamic acid that might also be involved in catalysis .

The structure of carbon-nitrogen hydrolase has four layers (α/β/β/α) containing mixed β-sheets.
SCP2 sterol-binding domain superfamily (SCP2_sterol-bd_dom_sf)
Type: Homologous_superfamily

This domain is involved in binding sterols, and is found in proteins such as SCP2. This domain has a 3-layer α/β/α fold, composed of α/β(3)/(crossover)/β/(α)/β.
Cloacin immunity protein superfamily (Cloacn_immnty_sf)
Type: Homologous_superfamily

The cloacin immunity protein complexes with cloacin in equimolar quantities and inhibits it by binding with high affinity to the cloacin C-terminal catalytic domain. The immunity protein is relatively small, containing 85 amino acids.

An extra ribosome binding site has been found to precede the immunity gene on the polycistronic Clo DF13 mRNA , which perhaps accounts for the fact that, in cloacinogenic cells, more immunity protein than cloacin is synthesised . Comparison of the complete amino acid sequence of the Clo DF13 immunity protein with that of the Col E3 and Col E6 immunity proteins reveals extensive similarities in primary structure, although Col E3 and Clo DF13 immunity proteins are exchangeable only to a low extent
in vivo
and
in vitro
.

The cloacin structure has a β(2)-α-β(2) fold with antiparallel β-sheet.
Coactivator CBP, KIX domain superfamily (KIX_dom_sf)
Type: Homologous_superfamily

Transcriptional activators are believed to stimulate gene expression via protein-protein interactions with the basal machinery. The cAMP-regulated transcription factor CREB has been shown to stimulate target gene expression, in part by associating with the coactivator paralogues p300 and CREB binding protein (CBP). CBP and P300 bind to the Ser-133-phosphorylated kinase-inducible domain (KID) of CREB via a region of approximately 90 residues referred to as the KIX domain, which is highly conserved in CBP homologues from Caenorhabditis elegans and Drosophila melanogaster. In addition to CREB, the KIX domain of CBP also recognises the transactivation domains of other nuclear factors, including Myb, Jun, cubitus interruptus, and HTLV-1 virally encoded Tax protein. Thus the KIX domain appears to be a common docking site on CBP for many transcriptional activators. The KIX domain is found in association with other domains, such as the bromodomain, the ZZ-type zinc finger, or the TAZ-type zinc finger .

The KIX domain of CBP is composed of three mutually interacting α helices, designated alpha1, alpha2 and alpha3, and two short 3(10) helices G1 and G2, that together with the interconnecting loops define a compact structural domain with an extensive hydrophobic core. Helices alpha1 and alpha3 constitute the primary interacting surface for the phosphorylated KID domain (pKID), forming a hydrophobic patch on the protein surface that is large enough to accommodate up to 3 turns of an amphipathic α helix, designated alphaB, in pKID. A second α helix in pKID, referred to as alphaA, interacts with a different face of the alpha3 helix of KIX. The two helices of pKID are arranged at an angle of about 90 degree and essentially wrap around the alpha3 helix of KIX .
Rabenosyn, Rab binding domain superfamily (Rbsn_Rab-bd_sf)
Type: Homologous_superfamily

Rabenosyn-5 (Rbsn) is a multivalent effector with interacts with the Rab family. Rsbn contains distinct Rab4 and Rab5 binding sites within residues 264-500 and 627-784 respectively . Rab proteins are GTPases involved in the regulation of all stages of membrane trafficking .

The structure of the Rab-binding sites reveals an antiparallel helical hairpin .
AvrPto superfamily (AvrPto_sf)
Type: Homologous_superfamily

This superfamily is represented by the bacterial effector protein AvrPto, from Pseudomonas syringae and in particular by the central core region of the protein that consists of a three-helix bundle motif. AvrPto is part of a type III secretion system from P.syringae which is involved in the bacterial speck disease of tomato. In resistant plants, AvrPto interacts with the host Pto kinase, which elicits an antibacterial defence response. In plants lacking resistance, the Pto kinase is not present and AvrPto acts as a virulence factor, promoting bacterial growth .
BAG domain superfamily (BAG_dom_sf)
Type: Homologous_superfamily

BAG domains are present in Bcl-2-associated athanogene 1 and silencer of death domains. The BAG proteins are modulators of chaperone activity; they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to the serine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1 signalling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that encourages cells to proliferate in normal conditions but become quiescent under a stressful environment .

BAG-family proteins contain a single BAG domain, except for human BAG-5, which has four BAG repeats . The BAG domain is a conserved region located at the C-terminal of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. The BAG domain is evolutionarily conserved, and BAG domain containing proteins have been described and/or proven in a variety of organisms, including Mus musculus (Mouse), Xenopus spp., Drosophila spp., Bombyx mori (Silk moth), Caenorhabditis elegans, Saccharomyces cerevisiae (Baker's yeast), Schizosaccharomyces pombe (Fission yeast), and Arabidopsis thaliana (Mouse-ear cress).

The BAG domain has 110-124 amino acids and is comprised of three anti-parallel α-helices, each approximately 30-40 amino acids in length. The first and second helices interact with the serine/threonine kinase Raf-1, and the second and third helices are the sites of the BAG domain interaction with the ATPase domain of Hsc70/Hsp70. Binding of the BAG domain to the ATPase domain is mediated by both electrostatic and hydrophobic interactions in BAG-1 and is energy-requiring.
GAR domain superfamily (GAR_dom_sf)
Type: Homologous_superfamily

The GAR (Gas2-related) domain is common in plakin family members and Gas2 family members. It has been shown to bind to microtubules probably through the flexible, positively charged central β-sheet formed by by five antiparallel β-strands .

This domain has an α-β(5)-α fold with two layers (α/β) consisting of meander antiparallel sheet.
STAT transcription factor, N-terminal domain superfamily (STAT_N_sf)
Type: Homologous_superfamily

The STAT protein (Signal Transducers and Activators of Transcription) family contains transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors, hence they act as signal transducers in the cytoplasm and transcription activators in the nucleus . The N-terminal domain of STAT is responsible for protein interactions. This domain has a multi-helical structure assembled into a hook-like structure .
Adaptor protein Cbl, N-terminal domain superfamily (Adaptor_Cbl_N_dom_sf)
Type: Homologous_superfamily

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 N-terminal four-helical bundle domain superfamily. This domain can also be found in the N terminus of mammalian MLKL, a pseudokinase essential for TNF-alpha-induced necroptosis . The four-helical bundle (NB) domain of MLK is involved in oligomerization to facilitate plasma membrane targeting through the low-affinity binding of NB to phosphorylated inositol polar head groups of phosphatidylinositol phosphate (PIP) phospholipids .
Alpha trans-inducing (Alpha-TIF) superfamily (Alpha_TIF_sf)
Type: Homologous_superfamily

Alpha-TIF (VP16) from Herpes Simplex virus is an essential tegument protein involved in the transcriptional activation of viral immediate early (IE) promoters (alpha genes) during the lytic phase of viral infection. VP16 associates with cellular transcription factors to enhance transcription rates, including the general transcription factor TFIIB and the transcriptional coactivator PC4. The N-terminal residues of VP16 confer specificity for the IE genes, while the C-terminal residues are responsible for transcriptional activation. Within the C-terminal region are two activation regions that can independently and cooperatively activate transcription . VP16 forms a transcriptional regulatory complex with two cellular proteins, the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 . VP16 is an alpha/beta protein with an unusual fold. Other transcription factors may have a similar topology.
Cytochrome c oxidase, subunit VIIa superfamily (Cyt_c_oxidase_su7a_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptidic subunits. This superfamily is composed of the heart and liver isoforms of cytochrome c oxidase subunit VIIa. Subunit VIIa has two tissue-specific isoforms that are expressed in a developmental manner. VIIa-H is expressed in heart and skeletal muscle but not smooth muscle. VIIa-L is expressed in liver and non-muscle tissues .
Poxvirus chemokine inhibitor superfamily (Pox_vCCI-like_sf)
Type: Homologous_superfamily

This superfamily of poxvirus secreted proteins (also known as T1 and A41) interact with members of both the CC and CXC superfamilies of chemokines. It has been suggested that these secreted proteins modulate leukocyte influx into virus-infected tissues .

The structure of the Vaccinia virus protein A41 (also known as chemokine inhibitor vCCI), a virulence factor that is representative of this group, has been solved. It consists of a β-sandwich topology .
Phospholipase A1 superfamily (PLipase_A1_sf)
Type: Homologous_superfamily

Outer membrane phospholipase A (OMPLA) is an integral membrane phospholipase, which is present in many Gram-negative bacteria and has a broad substrate specificity

. The role of OMPLA has been most thoroughly studied in Escherichia coli,
where it participates in the secretion of bacteriocins. Bacteriocin release is triggered by a lysis protein (bacteriocin release protein or BRP), followed by a phospholipase dependent accumulation of lysophospholipids and free fatty acids in the outer membrane . The reaction products enhance the permeability of the outer membrane, which allows the semispecific secretion of bacteriocins. One speculative function of OMPLA is related to organic solvent tolerance in bacteria.
Phosphotransferase system, lactose/cellobiose-type IIA subunit superfamily (PTS_IIA_lac/cel_sf)
Type: Homologous_superfamily

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The lactose/cellobiose-specific superfamily are one of four structurally and functionally distinct group IIA PTS system enzymes. This superfamily of proteins normally function as a homotrimer, stabilised by a centrally located metal ion . Separation into subunits is thought to occur after phosphorylation. It has a spectrin repeat-like fold which consists of three helices arranged in a close bundle with left-handed twist going up-and-down.
Guanylate-binding protein, C-terminal domain superfamily (Guanylate-bd_C_sf)
Type: Homologous_superfamily

Guanylate-binding protein is a GTPase that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups: the small 47-kd GTPases, the Mx proteins, and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class. In humans, there are seven GBPs (hGBP1-7) . Structurally, hGBP1 consists of two domains: a compact globular N-terminal domain harbouring the GTPase function (

), and an α-helical finger-like C-terminal domain. Human GBP1 is secreted from cells without the need of a leader peptide, and has been shown to exhibit antiviral activity against Vesicular stomatitis virus and Encephalomyocarditis virus, as well as being able to regulate the inhibition of proliferation and invasion of endothelial cells in response to IFN-gamma .

This entry represents the C-terminal domain superfamily of the guanylate-binding protein.
Cytochrome b-c1 complex subunit 7 superfamily (QCR7_sf)
Type: Homologous_superfamily

Cytochrome b-c1 complex subunit 7 (QCR7, also known as UQCRB) is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. QCR7 is involved in redox-linked proton pumping .