SII-SWORD/CoKE huggingface dataset:
Metalloprotease TldD/PmbA superfamily (TldD/PmbA_sf)
Type: Homologous_superfamily

This entry represents a group of metalloproteases including TdlD and PmbA (also known as TldE). The tertiary structure of the Escherichia coli TldD/TldE complex has been solved, and shows that the TldD subunit is the active peptidase, binding a single zinc ion at an HEXXXH motif in which the glutamic acid is a substrate-binding residue and the two histidines are zinc ligands. The third zinc ligand is a cysteine, C-terminal to the HEXXXH motif. TldE by itself has no catalytic activity, does not bind zinc, and does not carry the HEXXXH motif . TldD and TldE were originally identified as regulators of DNA gyrase. Later, they are shown to be metalloproteases involved in CcdA degradation .

The structure of TldE/TldD consists of two different α+β domains. The first one is a duplication of an α-β(3)-α motif with two layers (α/β) with an antiparallel β-sheet. While the second one has a complex fold with a β-barrel.
CheW-like domain superfamily (CheW-like_dom_sf)
Type: Homologous_superfamily

This entry represents the CheW-like domain superfamily.

The CheW-like domain is an around 150-residue domain that is found in proteins involved in the two-component signaling systems regulating bacterial chemotaxis. Two components systems are composed of a receptor kinase, which monitors the environmental conditions and its substrate, the response regulator, which acts as a binary switch depending on the phosphorylation state. In Escherichia coli, the signal transduction pathway for chemotaxis consists of specialised membrane receptors, termed chemotaxis transducers; a CheA-CheY two-component system, which transmits the signal from transducers to flagellar motors; and a docking protein, CheW, which couples the CheA histidine kinase to transducers. Whereas CheW is only made of a CheW-like domain, CheA additionally contains an HPt domain and an histidine kinase domain. The CheW-like domain has been shown to mediate the interaction between CheA and the adaptor protein CheW. Some bacteria contain another bifunctional protein, CheV, consisting of an N- terminal CheW-like domain and a C-terminal response regulatory domain. Although its precise function in chemotaxis is unknown, CheV probably acts in adaptation to attractants .

The CheW-like domain is composed of two β-sheet subdomains, each of which forms a loose five-stranded β-barrel around an internal hydrophobic core. The interactions between the subdomains are contributed by a third hydrophobic core sandwiched between the two β-sheet subdomains. The CheW-like structure is stabilised by extensive hydrophobic interactions .
Photosystem I PsaJ, reaction centre subunit IX superfamily (PSI_PsaJ_sf)
Type: Homologous_superfamily

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

This superfamily consists of the photosystem I reaction centre subunit IX or PsaJ from various organisms including Synechocystis sp. (strain PCC 6803), Pinus thunbergii (Green pine) and Zea mays (Maize). PsaJ (

) is a small 4.4kDa, chloroplast encoded, hydrophobic subunit of the photosystem I reaction complex whose function is not yet fully understood . PsaJ can be cross-linked to PsaF (

) and has a single predicted transmembrane domain. It has a proposed role in maintaing PsaF in the correct orientation to allow for fast electron transfer from soluble donor proteins to P700+ .
Smr domain superfamily (Smr_dom_sf)
Type: Homologous_superfamily

This entry represents the Smr domain superfamily.

The structure of the Smr domain has a β-α-β-α-β(2) fold. It is divided into two layers and the strand 4 is antiparallel to the rest.

The Smr domain is an around 90-residue domain found in:

The C-terminal region of the MutS2 proteins from bacteria and plants, such as Endonuclease MutS2 from Bacillus thuringiensis.

The small MutS related (Smr) proteins from bacteria and eukaryotes, including Ribosome rescue factor SmrB from Escherichia coli.

Other Smr domain-containing animal and fungal proteins, including human NEDD4-binding protein 2, which has 5'-polynucleotide kinase and nicking endonuclease activity .

These proteins could be involved in mismatch repair (MMR) or/and chromosome crossing-over and segregation. It has been proposed that the Smr domain acts as a nicking endonuclease .
Class XVIII myosin, motor domain (MYSc_Myo18)
Type: Domain

Many members of myosin class XVIII contain an N-terminal PDZ domain which is commonly found in proteins establishing molecular complexes. Mammals express a second isoform, Myo18B, that lacks the PDZ domain . They also contain a motor domain which does not exhibit ATPase activity, suggesting that these myosins function as an actin tether protein . They also have two IQ domains that probably bind light chains or related calmodulins and a C-terminal tail with two sections of coiled-coil domains, which are thought to mediate homodimerization . Myo18A has been implicated in stromal cell differentiation and Myo18B in tumor suppression .

This entry represents the motor domain.
BolA-like superfamily (BolA-like_sf)
Type: Homologous_superfamily

This superfamily consist of the morpho-protein BolA from Escherichia coli and its various homologues. In E. coli, over-expression of this protein causes round morphology and may be involved in switching the cell between elongation and septation systems during cell division . The expression of BolA is growth rate regulated and is induced during the transition into the the stationary phase . BolA is also induced by stress during early stages of growth and may have a general role in stress response. It has also been suggested that BolA can induce the transcription of penicillin binding proteins 6 and 5 . IbaG is a BolA homologue involved in acid resistance .

The structure of the BoIA protein has an α-β(2)-(α)-β fold divided into two layers (alpha/beta).
Nicotinate phosphoribosyltransferase-like, C-terminal (Nicotinate_pribotase-like_C)
Type: Homologous_superfamily

The nicotinate phosphoribosyltransferase catalyses the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP. Its structure contains a parallel β-sheet barrel.
DUF34/NIF3 superfamily (DUF34/NIF3_sf)
Type: Homologous_superfamily

This superfamily includes DUF34/metal-binding proteins (also known as GTP cyclohydrolase 1 type 2 proteins) from bacteria, NIF3 from budding yeasts and NIF3-like proteins from animals.

This entry includes the DUF34/metal-binding protein/NIF3 proteins, which are widely distributed across superkingdoms. They were previously annotated as GTP cyclohydrolase 1 type 2 and, recently, through a comprehensive literature review and integrative bioinformatic analyses it was revealed that annotations for these members are misleading as they were based on a single set of in vitro results examining the NIF3 homolog of Helicobacter pylori . Actually, they have varied phenotypes with the unifying functional role as metal-binding proteins .

NIF3 interacts with the yeast transcriptional coactivator Ngg1p which is part of the ADA complex, the exact function of this interaction is unknown .
Nop domain superfamily (Nop_dom_sf)
Type: Homologous_superfamily

This entry represents the Nop domain superfamily.

The Nop domain is present in various pre-RNA processing ribonucleoproteins (RNP):

Eukaryotic Prp31, part of a tri-snRNP complex. It is involved in pre-mRNA splicing.

Eukaryotic Nucleolar proteins 56 and 58 (Nop56 and Nop58), components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles.

Archaeal Nop5, an homologue of Nop56/Nop58.

The Nop domain is a RNP binding module, exhibiting RNA and protein binding surfaces. It is oval-shaped and exclusively α-helical .

U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31) is involved in pre-mRNA splicing as component of the spliceosome . This protein is required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome . It is associated with a progressive pigmentary retinopathy characterised by night vision blindness and loss of midperipheral visual field .

Nucleolar protein 56 and 58 (NOP56/58) are required for 60S ribosomal subunit synthesis . They are core components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles . In humans, NOP56 is associated with a type of slowly progressive neurodegenerative disorder characterised by late-onset ataxia followed by variable involvement of the motor neuron system .
AMMECR1 domain superfamily (AMMECR1_dom_sf)
Type: Homologous_superfamily

Nuclear protein AMMECR1, presently a protein of unknown function, is encoded by one of the genes affected by an X-linked deletion that causes the association of Alport syndrome, midface hypoplasia, intellectual disability and elliptocytosis in humans .

This entry represents the C-terminal region of AMMECR1 (approximately from residue 122 to 333), which is well conserved. Homologues appear in species ranging from bacteria and archaea to eukaryotes, including Protein PH0010 from Pyrococcus horikoshii . The high level of conservation of the AMMECR1 domain points to a basic cellular function, potentially in either the transcription, replication, repair or translation machinery . The AMMECR1 domain, which contains a 6-amino-acid motif (LRGCIG) that might be functionally important since it is strikingly conserved throughout evolution . The AMMECR1 domain consists of two distinct subdomains of different sizes. The large subdomain, which contains both the N- and C-terminal regions, consists of five α-helices and five β-strands. These five β-strands form an antiparallel β-sheet. The small subdomain consists of four α-helices and three β-strands, and these β-strands also form an antiparallel β-sheet. The conserved 'LRGCIG' motif is located at β(2) and its N-terminal loop, and most of the side chains of these residues point toward the interface of the two subdomains. The two subdomains are connected by only two loops, and the interaction between the two subdomains is not strong. Thus, these subdomains may move dynamically when the substrate enters the cleft. The size of the cleft suggests that the substrate is large, e.g., the substrate may be a nucleic acid or protein. However, the inner side of the cleft is not filled with positively charged residues, and therefore it is unlikely that negatively charged nucleic acids such as DNA or RNA interact at this site .
Class I myosin, motor domain (MYSc_Myo1)
Type: Domain

Class I myosins are present in a wide range of species from yeast to man, and have been implicated in actin cytoskeleton organization, cell motility, and endocytosis . They are actin-dependent molecular motors that play important roles in muscle contraction, cell motility, and organelle transport. S. cerevisiae has two class I myosins, Myo3 and Myo5, whereas S. pombe has only Myo1 . Vertebrates have eight class I myosin genes, six of which encode short-tailed forms (Myo1a, b, c, d, g, and h) and two of which encode long-tailed forms (Myo1e, f) . Myosin I, an unconventional myosin, does not form dimers .

Myosin I consist of a N-terminal motor domain, a C-terminal tail homology domain (TH1), and in some cases additional C-terminal structures that can mediate protein-protein interactions. The class 1 myosin motor domain contains motifs that are conserved across the myosin superfamily, including an actin binding cleft and a nucleotide binding pocket. When ATP is present, the motor has a low affinity for actin. Attachment to actin is accompanied by a force generating conformational change, referred to as a 'working stroke' .
Desulfoferrodoxin, ferrous iron-binding domain superfamily (Desulfoferrodoxin_Fe-bd_dom_sf)
Type: Homologous_superfamily

Desulfoferrodoxins contains two types of iron: an Fe-S4 site very similar to that found in desulfoferrodoxin from Desulfovibrio gigas, and an octahedral coordinated high-spin ferrous site most probably with nitrogen/oxygen-containing ligands. Due to this rather unusual combination of active centres, this novel protein is named desulfoferrodoxin .

This domain superfamily has an immunoglobulin-like β-sandwich fold, composed of seven strands in two sheets.
CbiD superfamily (CbiD_sf)
Type: Homologous_superfamily

CbiD is a SAM-dependent methyltransferase essential for cobalamin biosynthesis in both Salmonella typhimurium and Bacillus megaterium . A deletion mutant of CbiD suggests that this enzyme is involved in C-1 methylation and deacylation reactions required during the ring contraction process in the anaerobic pathway to cobalamin (similar role as CobF) . The CbiD protein has a putative S-AdoMet binding site . CbiD has no counterpart in the aerobic pathway.

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .
Damage-control phosphatase ARMT1-like, metal-binding domain superfamily (ARMT-1-like_metal-bd_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in Damage-control phosphatases ARMT1, YMR027W from S. cerevisiae (

) and At2g17340 from Arabidopsis thaliana, and it is also found at the C-terminal portion of eukaryotic pantothenate kinases . Despite a first characterization of ARMT1 as a carboxyl methyltransferase, a second study suggests that these proteins are hydrolases whose function is to limit potentially harmful buildups of phosphometabolites . They are metal-dependent phosphatases involved in metabolic damage-control processes termed "damage pre-emption" or "housecleaning". Crystal structure of damage-control phosphatase At2g17340 revealed a novel protein fold and several conserved residues coordinating a metal ion (probably Mg2) with high degree of conservation suggesting that the metal-binding site is central for the function of this domain .
Fructose-1,6-bisphosphatase, class V superfamily (FBPase_V_sf)
Type: Homologous_superfamily

Fructose-1,6-bisphophatase (FBPase) catalyses the hydrolysis of D-fructose-1,6-bisphosphate (FBP) to D-fructose-6-phopshate (F6P) and orthophosphate, and is a key enzyme in gluconeogenesis . Three different groups of FBPases have been identified in eukaryotes and bacteria (FBPase I-III) . None of these groups have been found in archaea so far, though a new group of FBPases (FBPase IV) which also show inositol monophosphatase activity has recently been identified in archaea .

Proteins in this entry are though to represent a new group of FBPases (FBPase V) which are found in thermophilic archaea and a hyperthermophilic bacterium Aquifex aeolicus . The characterised members of this group show strict substrate specificity for FBP and are suggested to be the true FBPase in these organisms . A structural study suggests that FBPase V has a novel fold for a sugar phosphatase, forming a four-layer α-β-β-α sandwich, unlike the more usual five-layered α-β-α-β-α arrangement . The arrangement of the catalytic side chains and metal ligands was found to be consistent with the three-metal ion assisted catalysis mechanism proposed for other FBPases.
Spo11/DNA topoisomerase VI subunit A superfamily (Spo11/TopoVI_A_sf)
Type: Homologous_superfamily

This entry represents Spo11, a meiotic recombination protein found in eukaryotes, and subunit A of topoisomerase VI, a type IIB topoisomerase found predominantly in archaea . These two types of proteins share structural homology.

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. They can be 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 . Topoisomerase VI is a type IIB enzymes that assembles as a heterotetramer, consisting of two A subunits required for DNA cleavage and two B subunits required for ATP hydrolysis. The B subunit is structurally similar to the ATPase domain of type IIA topoisomerases, but the A subunit is distinct, and instead shares homology with the Spo11 protein.
V-type ATP synthase subunit C/D subunit superfamily (ATPase_csu/dsu_sf)
Type: Homologous_superfamily

This entry represents subunits C and D of V-ATPases. There is more than one type of D subunit in V-ATPases, where the D1 subunit is ubiquitous, while the D2 subunit has limited tissue expressivity, possibly to account for differential functions, targeting or regulation of V-ATPase activity .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

The V-ATPases (or V1V0-ATPase) and A-ATPases (or A1A0-ATPase) are each composed of two linked complexes: the V1 or A1 complex contains the catalytic core that hydrolyses/synthesizes ATP, and the V0 or A0 complex that forms the membrane-spanning pore. The V-ATPase folding, localisation, and stability is made possible through the formation of a luminal glycan coat by the glycolipids and the glycosylated V0 subunits . The V- and A-ATPases both contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis . The V- and A-ATPases more closely resemble one another in subunit structure than they do the F-ATPases, although the function of A-ATPases is closer to that of F-ATPases.
F420-dependent methylenetetrahydromethanopterin dehydrogenase superfamily (MTD_sf)
Type: Homologous_superfamily

This archaeal enzyme superfamily is involved in formation of methane from carbon dioxide

. The enzyme requires coenzyme F420 .

The structure of this enzyme has a three layers (α/β/α) fold with parallel β-sheet of six strands.
Translin superfamily (Translin_sf)
Type: Homologous_superfamily

Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-stranded DNA ends generated by staggered breaks occuring at recombination hot spots . Translin folds into an α-α superhelix, consisting of two curved layers of α/α topology .

This entry also includes translin-associated protein X (TRAX), which was found to interact with translin .
NSP3 superfamily (NSP3_sf)
Type: Homologous_superfamily

This superfamily consists of rotaviral non-structural RNA binding protein 34 (NS34 or NSP3). The NSP3 protein has been shown to bind viral RNA. The NSP3 protein consists of 3 conserved functional domains; a basic region which binds ssRNA, a region containing heptapeptide repeats mediating oligomerisation and a leucine zipper motif . NSP3 may play a central role in replication and assembly of genomic RNA structures . Rotaviruses have a dsRNA genome and are a major cause cause of acute gastroenteritis in the young of many species .

The NPS3 homodimer fold has two domains, one all-alpha and the other α+β. It is asymmetric with each domain intertwining with its counterpart.
Class III myosin, motor domain (MYSc_Myo3)
Type: Domain

Myosin III is an actin-based motor protein with protein kinase activity . It has been shown to play a role in the vision process and in hearing in mammals . There are two paralogues of Myo3 in vertebrates, Myo3a and Myo3b, both known to be expressed in vertebrate retina and cochlea. They are thought to be crucial for photoreceptor and stereocilia ultrastructure maintenance . Class III myosins are characterised by the presence of an N-terminal protein kinase domain before their motor head domain. They are unconventional myosins that do not form dimers . The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases.
Serine protease inhibitor-like superfamily (Ser_inhib-like_sf)
Type: Homologous_superfamily

This superfamily is part of proteinase inhibitors, as well as in many extracellular proteins. The domain typically contains ten cysteine residues that form five disulphide bonds. The cysteine residues that form the disulphide bonds are 1-7, 2-6, 3-5, 4-10 and 8-9.
PAZ domain superfamily (PAZ_dom_sf)
Type: Homologous_superfamily

This domain superfamily is named after the proteins Piwi Argonaut and Zwille. It is also found in the CAF protein from Arabidopsis thaliana. The function of the domain is unknown but has been found in the middle region of a number of members of the Argonaute protein family, which also contain the Piwi domain (

) in their C-terminal region . Several members of this family have been implicated in the development and maintenance of stem cells through the RNA-mediated gene-quelling mechanisms associated with the protein DICER.
ParB/Sulfiredoxin superfamily (ParB/Sulfiredoxin_sf)
Type: Homologous_superfamily

The structure of ParB/Sulfiredoxin has a β-α-β(2)-α-β-α fold with mixed β sheet forming a partly open barrel.

ParB plays a vital role in chromosome partitioning and nucleoid occlusion. These proteins are essential for ensuring proper chromosome segregation during cell division by binding to the DNA origin of replication and localising to both poles of the predivisional cell following DNA replication. ParB proteins share significant sequence and structural similarity with Sulfiredoxin (Srx), a sulfinic acid reductase identified in eukaryotes. Sequence comparison and phylogenetic analysis of the Srx and ParB protein families suggest that Srx evolved via truncation of ParB, resulting in the removal of the entire C-terminal half of the protein including the HTH domain . ParB comprises three highly conserved domains: an N-terminal nucleotide-binding domain (NBD)

, a central helix-turn-helix parS-binding domain

, non-structured linker region, and a C-terminal dimerisation domain

that tightly links the two subunits of the ParB dimer .