SII-SWORD/CoKE huggingface dataset:
Melampsora avirulence protein AvrL567 superfamily (Melampsora_AvrL567_sf)
Type: Homologous_superfamily

AvrL567 is a protein from the fungal pathogen Melampsora lini which induces plant disease resistance in flax plants . Avirulence proteins trigger the resistance response in plants by interacting with plant disease-resistance proteins . The protein has a novel β-barrel-like fold .
Periplasmic metal-binding protein Tp34-type superfamily (Tp34-type_sf)
Type: Homologous_superfamily

This entry represents metal-binding periplasmic proteins. Tp34 has been classified together with other proteins in a group of uncharacterised proteins probably involved in high affinity Fe2+ transport. However, the structural and functional aspects of this group of proteins remain undetermined. Tp34 may bind zinc and the iron-sequestering lactoferrin and may have a role in metal ion homeostasis .
YcfL-like superfamily (YcfL-like_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical bacterial proteins. Several members are described as putative lipoproteins and are often known as YcfL. Their function is unknown.
MucB/RseB, C-terminal domain superfamily (MucB/RseB_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of sigma-E factor regulatory protein RseB and sigma factor AlgU regulatory protein MucB. MucB plays a role in the differentiation of P. aeruginosa into the alginate-producing form . RseB negatively modulates the activity of sigma-E (RpoE) by stabilizing RseA under non-stress conditions . The small C-terminal domain of RseB is responsible for interaction with RseA .
Protein Z, RING-type zinc finger superfamily (Z_RING-type_Znf_sf)
Type: Homologous_superfamily

This entry represents the RING zinc finger domain of 'RING finger protein Z', a small polypeptide found in some negative-strand RNA viruses including Lassa fever virus, which plays a crucial role in virion assembly and budding. RING finger Z has been shown to interact with several host proteins, including promyelocytic leukemia protein and the eukaryotic translation initiation factor 4E . It is sufficient in the absence of any other viral proteins to release virus-like particles from the infected cell . This protein is also responsible for arenavirus superinfection exclusion; expression of this protein in a host cell strongly and specifically inhibits areanavirus transcription and replication .

The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions . There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'. The RING domain is a protein interaction domain which has been implicated in a range of diverse biological processes. Several 3D-structures for RING-fingers are known . The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is:

C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C

Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second.
Fiber protein, C-terminal domain superfamily (Fiber_prot_C_sf)
Type: Homologous_superfamily

This entry represents a C-terminal part of the head domain of the dsDNA viruses, no RNA stage, Adenovirus. This is a globular head domain with an anti-parallel β-sandwich fold formed by two four-stranded β-sheets with the same overall topology as human adenovirus fibre heads. This C-terminal domain is the receptor-binding domain of the avian adenovirus long fibre .
Mre11, capping domain (Mre11_capping_dom)
Type: Homologous_superfamily

This superfamily represents the Mre11 capping domain.

The MRN complex is a multi-subunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2, and is involved in checkpoint signalling, double-strand break (DSB) repair, DNA replication, maintenance of telomere integrity and meiosis, promoting genomic stability . Mre11 has an intrinsic DNA-binding activity that is stimulated by Rad50 on its own or in combination with Nbs1 . This protein dimerises via phosphodiesterase domains flanked by an α/β capping domain, which creates a U-shaped particle with a broad DNA/Rad50 binding cleft .
Integrase, DNA-binding domain superfamily (Integrase_DNA-bd_sf)
Type: Homologous_superfamily

This domain is found at the N terminus of a wide variety of phage integrase proteins. It is predicted to bind DNA.
Suppressor of fused, C-terminal domain superfamily (SUFU_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of eukaryotic suppressor of fused (Sufu) proteins. It folds into a domain that comprises a four-stranded and a six-stranded β-sheet, both with mixed topologies, which are connected by two antiparallel α-helices .

Sufu is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade . It functions by binding to these proteins and preventing their translocation to the nucleus. The Sufu C-terminal domain binds to the N-terminal of Gli/Ci, while the N-terminal of Sufu binds to the C-terminal of Gli/Ci. This dual binding mechanism is likely to be an evolutionary advancement in this signalling cascade, which is not present in bacterial homologues .
Gingipain propeptide superfamily (Gingipain_propep_sf)
Type: Homologous_superfamily

Gingipains are proteinases from Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis. They belong to MEROPS peptidase family C25. There are three types: Arg-specific proteinases RgpA, and RgpB, and the Lys-specific proteinase Kgp. All three gingipain precursors contain a propeptide of around 200 amino acids in length that is removed during maturation. It has been shown that gingipain propeptides are capable of inhibiting their mature cognate proteinases . Proteins homologous to the gingipain precursor are known from many other bacteria, some archaea and some eukaryotes.
Velvet domain superfamily (Velvet_dom_sf)
Type: Homologous_superfamily

The fungus-specific velvet family of regulatory proteins plays a key role in coordinating secondary metabolism and differentiation processes such as asexual or sexual sporulation and sclerotia or fruiting body formation. These velvet regulators are present in most parts of the fungal kingdom from chytrids to basidiomycetes. Velvet proteins interact with each other, alone ("homodimers"), in various combinations ("heterodimers"), and also with other proteins. The velvet proteins share a homologous region comprising about 150 amino acids, which lack significant sequence similarity to any other known proteins. The velvet domain is involved in specific DNA binding as well as in the dimerization of the different velvet proteins, resulting in the formation of homo- and heterodimers .

The velvet domain is an RHD-like domain related to NF-kappaB. It folds into a highly twisted β-sandwich composed of seven antiparallel β-strands. One side of the β-sandwich is involved in dimer formation, whereas the other one is flanked by several loops of which two fold into an α-helix. These α-helical fragments are located between β-strands 2 and 3 and at the C terminus .
GBBH-like, N-terminal domain superfamily (GBBH-like_N_sf)
Type: Homologous_superfamily

Gamma-butyrobetaine hydroxylase (GBBH), also known as gamma-butyrobetaine dioxygenase, is an alpha-ketoglutarate-dependent dioxygenase that catalyses the biosynthesis of L-carnitine by hydroxylation of gamma-butyrobetaine (GBB). GBBH is a dimeric enzyme. The monomer consists of a catalytic double-stranded β-helix domain and a smaller N-terminal domain. The N-terminal domain has a bound Zn ion, which is coordinated by three cysteines and one histidine. The N-terminal domain facilitates the assembly of a symmetric head-to-tail dimer formation through the interface with the C-terminal domain of the other monomer .

This domain superfamily is also found in another hydroxylase of the biosynthetic pathway of L-carnitine, the first enzyme of the pathway, known as trimethyllysine dioxygenase (TMLD). Like GBBH, TMLD is a non-heme ferrous-iron dioxygenase that requires alpha-ketoglutarate, Fe2+, and molecular oxygen as cofactors .
Toxin MqsR superfamily (MqsR_sf)
Type: Homologous_superfamily

MqsR is a bacterial toxin that acts as an mRNA interferase . MqsR is the gene most highly upregulated in E. coli persister cells and it plays an essential role in biofilm regulation and cell signalling . It forms part of a bacterial toxin-antitoxin TA system, and as expected for a TA system, the expression of the MqsR toxin leads to growth arrest, while co-expression with its antitoxin, MqsA, rescues the growth arrest phenotype. In addition, MqsR associates with MqsA to form a tight, non-toxic complex and both MqsA alone and the MqsR:MqsA2:MqsR complex bind and regulate the mqsR promoter. The structure of MqsR shows that it is a member of the RelE/YoeB family of bacterial RNases that are structurally and functionally characterised bacterial toxins .
Imidazole glycerol phosphate dehydratase domain superfamily (IGPD_sf)
Type: Homologous_superfamily

Imidazoleglycerol-phosphate dehydratase (IGPD;

) catalyzes the dehydration of imidazole glycerol phosphate to imidazole acetol phosphate, the sixth step of histidine biosynthesis in plants and microorganisms where the histidine is synthesized de novo. There is an internal repeat in the protein domain that is related by pseudo-dyad symmetry, perhaps as a result of an ancient gene duplication. The apo-form of IGPD exists as a catalytically inactive trimer which, in the presence of specific divalent metal cations such as manganese (Mn2+), cobalt (Co2+), cadmium (Cd2+), nickel (Ni2+), iron (Fe2+) and zinc (Zn2+), assembles to form a biologically active high molecular weight metalloenzyme; a 24-mer with 4-3-2 symmetry. Each 24-mer has 24 active sites, and contains around 1.5 metal ions per monomer, each monomer contributing residues to three separate active sites.

IGPD enzymes are monofunctional in fungi, plants, archaea and some eubacteria while they are encoded as bifunctional enzymes in other eubacteria, such that the enzyme is fused to histidinol-phosphate phosphatase, the penultimate enzyme of the histidine biosynthesis pathway. The histidine biosynthesis pathway is a potential target for development of herbicides, and IGPD is a target for the triazole phosphonate herbicides .
V-type ATPase subunit E, C-terminal domain superfamily (ATPase_E_C)
Type: Homologous_superfamily

Proton-translocating ATPases (H+-ATPases) are rotary enzymes that couple proton (or Na+) translocation across membranes with ATP synthesis or hydrolysis. There are three types of these protein complexes: F-, V- and A-type ATPases. F-type ATPases, better known as F1F0 ATP synthases, use energy from proton translocation across an electrochemical gradient to synthesize ATP. In contrast, vacuolar or V-type ATPases work in reverse by actively pumping protons through membranes using energy derived from ATP hydrolysis. Although eukaryotes contain both F- and V-ATPases, each highly specialized in its physiological function, archaea and eubacteria typically contain only one complex. Most eubacteria contain F-type ATPases, but some eubacteria and all known archaea contain complexes that are evolutionary closer to V-ATPases and are referred to as A-ATPases/synthases .

This entry represents a domain found in subunit E from V-ATPases and A-ATPase/synthases. Subunit E appears to form a tight interaction with subunit G, which together may act as stators to prevent certain subunits from rotating with the central rotary element, much in the same way as the F0 complex subunit B does in F-ATPases . In addition to its key role in stator structure, subunit E appears to have a role in mediating interactions with putative regulatory subunits .

Subunit E is a long, two domain protein with a C-terminal globular domain . It contains hendecad repeats (11/3) along the entirety of its N-terminal helix. The hendecad pattern is of the form a-b-c-d-e-f-g-h-i-j-k, with hydrophobic residues at positions a,d,e,h resulting in a right handed coiling of the helices . The C-terminal half of subunit E forms the majority of the head group and consists of a globular domain, which contains a four-stranded b-sheet and two a-helices followed by a C-terminal a-helical tail .
Rad61, Wapl domain superfamily (Rad61_Wapl_sf)
Type: Homologous_superfamily

The Wapl domain is found at the C terminus of fungal Wpl1 proteins (also known as Rad61), which are subunits of a complex that inhibits sister chromatid cohesion. The Wapl domain binds to the ATPase domain of cohesin subunit Smc3 .
ATPase, V1 complex, subunit H, C-terminal domain superfamily (ATPase_V1-cplx_hsu_C_sf)
Type: Homologous_superfamily

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents the C-terminal domain of subunit H (also known as Vma13p) found in the V1 complex of V-ATPases. This subunit has a regulatory function, being responsible for activating ATPase activity and coupling ATPase activity to proton flow . The yeast enzyme contains five motifs similar to the HEAT or Armadillo repeats seen in the importins, and can be divided into two distinct domains: a large N-terminal domain consisting of stacked α helices, and a smaller C-terminal α-helical domain with a similar superhelical topology to an armadillo repeat .
OspF/SpvC superfamily (OspF/SpvC_sf)
Type: Homologous_superfamily

This entry includes the virulence protein SpvC and the phosphothreonine lyase OspF.

The spv region of the Salmonella virulence plasmids consists of five genes located on an 8-kb fragment, shown to be essential for virulence in mice . SpvC (also known as mkfA and VirA ) is part of this gene cluster and is utilised by the microbe upon entry into macrophages, although the exact mechanism is unclear.
BRO1 domain superfamily (BRO1_sf)
Type: Homologous_superfamily

The BRO1 domain is a protein domain of ~390 residues in length. It occurs in a number of eukaryotic proteins, such as yeast BRO1 and human PDCD6IP/Alix, which are involved in protein targeting to the vacuole or lysosome. The BRO1 domain of fungal and mammalian proteins binds with multivesicular body components (ESCRT-III proteins) such as yeast Snf7 and mammalian CHMP4b, and can function to target BRO1 domain-containing proteins to endosomes .

The BRO1 domain has a boomerang shape composed of 14 α-helices and 3 β-sheets. It contains a TPR-like substructure in the central part . The C terminus is less conserved.
Antitermination protein Q superfamily (Antitermination_sf)
Type: Homologous_superfamily

This entry consists of antitermination proteins found in bacteriophages, such as protein Q from phage lambda, and some bacterial homologues. Protein Q positively regulates expression of the phage late gene operon by binding to the bacterial host RNA polymerase (RNAP) and modifying it. This protein binds a specific DNA Q-binding element (QBE) and interacts with RNAP. The modified RNAP can read without pausing and through transcription terminators preceding late genes . It participates in the lysis-lysogeny decision by activating the expression of the late lytic genes . The structure of Q from bacteriophage 21 revealed that it forms a torus, that narrows and extends the RNAP RNA-exit channel and extrudes the linked RNA, preventing the formation of pause and terminator hairpins .
Spore germination GerAC, C-terminal domain superfamily (Spore_GerAC_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of spore germination proteins predominantly found in firmicutes, including GerAC (also known as spore germination protein A3, -KC, and -AC from Bacillus subtilis .

The GerAA, -AB, and -AC proteins of the Bacillus subtilis spore are required for the germination response to L-alanine as the sole germinant. Members of GerAC family are thought to be located in the inner spore membrane. Although the function of this family is unclear, they are likely to encode the components of the germination apparatus that respond directly to this germinant, mediating the spore's response .
Peptidase M1, LTA-4 hydrolase/aminopeptidase, C-terminal domain superfamily (M1_LTA-4_hydro/amino_C_sf)
Type: Homologous_superfamily

This C-terminal domain is found in peptidases belonging to MEROPS peptidase family M1, particularly: aminopeptidase-1 of Caenorhabditis elegans, aminopeptidase O, aminopeptidase B and the bifunctional leukotriene A4 (LTA-4) hydrolase/aminopeptidase.
Stage III sporulation protein AH-like superfamily (SpoIIIAH_sf)
Type: Homologous_superfamily

Stage III sporulation protein AH (SpoIIIAH) is a protein that is involved in forespore engulfment. It forms a channel with SpoIIIAH that is open on the forespore end and closed (or gated) on the mother cell end. This allows sigma-E-directed gene expression in the mother-cell compartment of the sporangium to trigger the activation of sigma-G forespore-specific gene expression by a pathway of intercellular signaling .
UL141-like superfamily (UL141-like_sf)
Type: Homologous_superfamily

UL141 is a a glycoprotein from herpesvirus species. Its N-terminal Ig-like β-sandwich domain binds to the cysteine-rich region of TRAIL-R2, a family of tumour necrosis factor receptor proteins. UL141 is both necessary and sufficient to retain TRAIL receptors in the ER, thereby preventing their cell surface expression and it is also necessary and sufficient to inhibit cell surface expression of CD155 .
FANCF, C-terminal domain superfamily (FANCF_C_sf)
Type: Homologous_superfamily

Fanconi anemia (FA) is a genomic instability syndrome caused by mutations in at least 13 distinct genes whose products function in a common DNA repair signaling pathway, the FA pathway. The FA pathway cooperates with other DNA repair proteins for resolving DNA interstrand cross-links during replication .

Fanconi anemia group F protein (FANCF) is a component of the FA core complex . FANCF regulates its own expression by methylation at both mRNA and protein levels. Methylation-induced inactivation of FANCF has an important role on the occurrence of ovarian cancers by disrupting the FA-BRCA pathway .

This entry represents the C-terminal region of the FANCF protein found in metazoa. The C-terminal domain has an helical repeat structure and is necessary for the proper assembly of the FA core complex .
GLE1-like superfamily (GLE1-like_sf)
Type: Homologous_superfamily

The members of this superfamily are sequences that are similar to the human protein GLE1 (

). This protein is localised at the nuclear pore complexes and functions in poly(A)+ RNA export to the cytoplasm .
YcnI-like superfamily (YcnI-like_sf)
Type: Homologous_superfamily

YcnI (also known as CutI) is a copper-responsive gene of Bacillus subtilis . It is homologous to an uncharacterised protein from Nocardia farcinica, which shares a conserved three-dimensional structure with cohesins and the reeler domain. Some proteins with this domain have C-terminal domains that bind copper

.
ArfGAP domain superfamily (ArfGAP_dom_sf)
Type: Homologous_superfamily

Proteins containing this domain include ARF1-directed GTPase-activating protein, the cycle control GTPase activating protein (GAP) GCS1 which is important for the regulation of the ADP ribosylation factor ARF, a member of the Ras superfamily of GTP-binding proteins . The GTP-bound form of ARF is essential for the maintenance of normal Golgi morphology, it participates in recruitment of coat proteins which are required for budding and fission of membranes. Before the fusion with an acceptor compartment the membrane must be uncoated. This step required the hydrolysis of GTP associated to ARF. These proteins contain a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. The ARFGAP domain display no obvious similarity to other GAP proteins.

The 3D structure of the ARFGAP domain of the PYK2-associated protein beta has been solved . It consists of a three-stranded β-sheet surrounded by 5 α helices. The domain is organised around a central zinc atom which is coordinated by 4 cysteines. The ARFGAP domain is clearly unrelated to the other GAP proteins structures which are exclusively helical. Classical GAP proteins accelerate GTPase activity by supplying an arginine finger to the active site. The crystal structure of ARFGAP bound to ARF revealed that the ARFGAP domain does not supply an arginine to the active site which suggests a more indirect role of the ARFGAP domain in the GTPase hydrolysis .
IFS superfamily (IFS_sf)
Type: Homologous_superfamily

Immunity factor for SPN (IFS) binds to and inhibits the SPN toxin. IFS inhibits SPN enzymatic activity by binding over the active site and completely blocking its access to beta-NAD+ .
Spt4 superfamily (Spt4_sf)
Type: Homologous_superfamily

This superfamily consists of several eukaryotic transcription initiation Spt4 proteins. Three transcription-elongation factors Spt4, Spt5, and Spt6 are conserved among eukaryotes and are essential for transcription via the modulation of chromatin structure. Spt4 and Spt5 are tightly associated in a complex, while the physical association of the Spt4-Spt5 complex with Spt6 is considerably weaker. It has been demonstrated that Spt4, Spt5, and Spt6 play roles in transcription elongation in both yeast and humans including a role in activation by Tat. It is known that Spt4, Spt5, and Spt6 are general transcription-elongation factors, controlling transcription both positively and negatively in important regulatory and developmental roles .
TAP42/TAP46-like superfamily (TAP42/TAP46-like_sf)
Type: Homologous_superfamily

The TOR signalling pathway activates a cell-growth program in response to nutrients . TIP41 interacts with TAP42 and negatively regulates the TOR signalling pathway . TAP42 is found in yeast and mammals, its homologue in plants is TAP46 . TAP46 plays an essential role in plant growth and development as a component of the TOR signalling pathway .
GpU-like superfamily (GpU-like_sf)
Type: Homologous_superfamily

This entry represents bacteriophage lambda, GpU, a minor tail protein. GpU plays an essential role in tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for the completion protein . GpU forms a hexameric ring within the tail structure since it spontaneously forms such rings in the presence of Mg2+ that match the size of the hexameric rings of gpV that comprise the bulk of the tail tube. However, prior to tail assembly, gpU remains monomeric . The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
FAIM1 domain superfamily (FAIM1_dom_sf)
Type: Homologous_superfamily

FAIM1 (Fas apoptotic inhibitory molecule 1) plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells .

FAIM1 contains two independently folding domains . The C-terminal domain folds as a non-conventional β-sandwich, and the N-terminal domain has a similar conformation containing eight antiparallel β-strands . This superfamily recognizes both of them.