SII-SWORD/CoKE huggingface dataset:
AAR2, C-terminal domain superfamily (AAR2_C_sf)
Type: Homologous_superfamily

Aar2 is a U5 small nuclear ribonucleoprotein (snRNP) particle assembly factor and part of Prp8, which forms a large complex containing U5 snRNA, Snu114, and seven Sm proteins (B, D1, D2, D3, E, F and G). Upon import of the complex into the nucleus, Aar2 phosphorylation leads to its release from Prp8 and replacement by Brr2p, thus playing an important role in Brr2p regulation and possibly safeguarding against non-specific RNA binding to Prp8 . Aar2p binds directly with the RNaseH-like domain in the C-terminal region of Prp8p . In yeast, Aar2 protein is involved in splicing pre-mRNA of the a1 cistron and other genes important for cell growth .

This entry consists of the C-terminal domain of eukaryotic Aar2 and Aar2-like proteins. This domain consists of 9 α-helices, 1 π-helix and 1 3(10)-helix.
Two-component sensor protein CpxA, periplasmic domain superfamily (CpxA_peri_sf)
Type: Homologous_superfamily

The Cpx system is one of extracytoplasmic stress response systems (ESR) found in Gram-negative bacteria. ESRs are operated by a two-component signalling system which consists of a sensory histidine kinase (HK) and a response regulator (RR) as basal elements. In the Cpx system, CpxA is the inner membrane-spanning, sensory HK .

This entry represents the periplasmic domain (also known as the VpCpxA-peri domain) of CpxA from Vibrio parahaemolyticus , Klebsiella pneumoniae , and similar proteins from gammaproteobacteria. The VpCpxA-peri domain possesses a PAS fold that play a role in sensing envelope stress signals . It recognises KCl and RbCl .
AAR2, N-terminal domain superfamily (AAR2_N_sf)
Type: Homologous_superfamily

Aar2 is a U5 small nuclear ribonucleoprotein (snRNP) particle assembly factor and part of Prp8, which forms a large complex containing U5 snRNA, Snu114, and seven Sm proteins (B, D1, D2, D3, E, F and G). Upon import of the complex into the nucleus, Aar2 phosphorylation leads to its release from Prp8 and replacement by Brr2p, thus playing an important role in Brr2p regulation and possibly safeguarding against non-specific RNA binding to Prp8 . Aar2p binds directly with the RNaseH-like domain in the C-terminal region of Prp8p . In yeast, Aar2 protein is involved in splicing pre-mRNA of the a1 cistron and other genes important for cell growth .

This entry consists of the N-terminal domain of eukaryotic Aar2 and Aar2-like proteins.
MxiM superfamily (MxiM_sf)
Type: Homologous_superfamily

MxiM, a Shigella pilot protein (also known as type 3 secretion system pilotin), is essential for the assembly and membrane association of the Shigella secretin MxiD. MxiM contains an orthologous secretin component and has a specific binding domain for the acyl chains of bacterial lipids . The C-terminal domain of MxiD hinders lipid binding to MxiM .

Structurally, MxiM consists of 10 β strands, 1 α helix and 1 3(10)-helix. These 10 β strands are arranged into a β barrel, which is discontinuous since the α helix interrupts the strands.
Glycosyl hydrolase family 63, N-terminal domain superfamily (Glyco_hydro_63N_sf)
Type: Homologous_superfamily

Glycoside hydrolases are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. More than 100 different families of glycoside hydrolases have been defined based on sequence similarity.

This entry represents the N-terminal β sandwich domain found in glycosyl hydrolase family 63 proteins . Glycosyl hydrolase family 63 is a family of eukaryotic enzymes that catalyse the specific cleavage of the non-reducing terminal glucose residue from Glc(3)Man(9)GlcNAc(2).
Major capsid protein, C-terminal domain superfamily (MCP_C_sf)
Type: Homologous_superfamily

The entry includes major capsid proteins (vp54 and vp72) found in Iridoviruses, Phycodnaviruses, Asfarviruses and Ascoviruses, which are all type II dsDNA viruses with no RNA stage. This is the most abundant structural protein and can account for up to 45% of virion protein . The structure of vp54 has been determined from Paramecium bursaria Chlorella virus 1 (PBCV-1), a very large icosahedral virus containing an internal membrane enclosed within a glycoprotein coat. The vp54 protein is a duplication consisting of two domains with a similar fold packed together like the nucleoplasmin subunits. The vp54 protein forms a trimer, where the domains are arranged around a pseudo 6-fold axis. The domains have a β-sandwich structure consisting of 8 strands in two sheets with a jelly-roll topology .
Matrix protein superfamily (BDV_M_sf)
Type: Homologous_superfamily

This entry represents the matrix protein M from negative-strand Bornaviridae viruses (BDV-M). Its most stable oligomeric form is a tetramer, and it lies beneath the viral envelope where it associates with the inner layer of the viral membrane. It bridges the gap between the nucleocapsid and the viral envelope thereby imparting structural integrity and individual form to the virus particle. Borna disease virus (BDV) is a neurotropic enveloped RNA virus causing a noncytolytic, persistent infection of the central nervous system in mammals. The order to which this virus belongs, Mononegavirales, also contains the Ebola, mumps, rabies and measles viruses, amongst other highly infectious agents .

Structural studies on this protein have shown that heterologously expressed BDV-M co-purifies with and protects ssRNA oligonucleotides taken up from the expression host. This has revealed the ability of BDV-M to bind RNA and lipid membranes simultaneously, thus expanding the repertoire of M-protein functionalities .
ThiC/Bza, core domain (ThiC/Bza_core_dom)
Type: Homologous_superfamily

ThiC is found within the thiamin biosynthesis operon and is involved in thiamin biosynthesis . It catalyses the synthesis of the hydroxymethylpyrimidine phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR) in a radical S-adenosyl-L-methionine (SAM)-dependent reaction .

BzaF, a radical SAM enzyme that catalyzes the conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI), is a paralogue of thiC .

This entry also includes 5-hydroxybenzimidazole synthase BzaA and BzaB. They are part of the bzaABCDE genes that are necessary and sufficient for the anaerobic biosynthesis of DMB (5,6-dimethylbenzimidazole), the "lower ligand" of vitamin B12 .

This superfamily represents the core domain of these enzymes. Within ThiC, this superfamily makes up the central domain and the cavity of this barrel contains the putative active site. Structurally, this domain consists of 8 β strands and 8 α helices arranged into a TIM barrel.
Type IV / VI secretion system, DotU superfamily (T4/T6SS_DotU_sf)
Type: Homologous_superfamily

At least two distinct groups of proteins, often encoded by adjacent genes, show sequence similarity due to homology between type IV secretion systems and type VI secretion systems. One is the IcmF family (

). The other group is the DotU family, which includes DotU from the Legionella pneumophila type IV secretion system. Many members of this protein family from type VI secretion systems have an additional C-terminal domain with OmpA/MotB homology

.
AmiS/UreI transporter superfamily (AmiSUreI_transpt_sf)
Type: Homologous_superfamily

Helicobacter pylori is a Gram-negative, ureolytic bacteria that can colonise the human stomach. It does not survive in a medium with a pH less than 4.0 unless urea is present, preferring a neutral pH. Gastric juice urea is able to rapidly access intrabacterial urease when the periplasmic pH falls below approximately 6.2 owing to pH-gating of a urea channel, UreI. UreI is a six-transmembrane segment protein that is homologous to the amiS genes of the amidase gene cluster and to UreI of Helicobacter hepaticus and Streptococcus salivarius. UreI in H. pylori and H. hepaticus can transport urea only at acidic pH, whereas that of S. salivarius is open at both neutral and acidic pH .

The amiS gene encodes an 18kDa protein with a high content of hydrophobic residues. It has six transmembrane helices. AmiB and AmiS resemble two components of an ABC transporter system .

This superfamily includes UreI and proton gated urea channel as well as putative amide transporters AmiS .
ATR13 superfamily (ATR13_sf)
Type: Homologous_superfamily

The avirulence protein ATR13 is expressed by the plant pathogen oomycete Hyaloperonospora. Such phytopathogenic oomycetes like the one that infects Arabidopsis, Hyaloperonospora arabidopsidis (Hpa), grow intercellularly, forming parasitic structures called haustoria. Haustoria play a role in feeding and suppression of host defence systems. A whole range of pathogen proteins, called effectors, are secreted across this haustorial membrane, a subset of which are further translocated across the plant plasma membrane by an unknown mechanism that is present in both plants and animals. ATR13 is an RxLR effector from the downy mildew oomycete, and is a very dynamic protein. It contains two surface-exposed patches of polymorphism, one of which is involved in the specific recognition by host R-genes. The R-gene-products detect the presence of the infection by recognising the effector proteins. Once detected, the host R-genes trigger apoptosis of the host cell. The R-gene-products carry a specific motif, RxLR, that is recognises the effector proteins .
Large ribosomal subunit protein eL22 superfamily (Ribosomal_eL22_sf)
Type: Homologous_superfamily

Ribosomal protein eL22 forms part of the 60S ribosomal subunit found in eukaryotes. Rattus norvegicus (Rat) eL22 is related to ribosomal proteins from other eukaryotes and is identical in amino acid sequence to human EAP, the EBER 1 (Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) encoded RNA) associated protein .
HupH, C-terminal domain superfamily (HupH_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal conserved domain found in bacterial hydrogenase expression proteins (HupH), which are necessary for hydrogenase synthesis. The precise function of HupH is unknown .
TEL2, C-terminal domain superfamily (TEL2_C_sf)
Type: Homologous_superfamily

This entry represents a conserved domain found in a group of proteins called telomere-length regulation TEL2, or clock abnormal protein-2, which are conserved from plants to humans. These proteins regulate telomere length and contribute to silencing of sub-telomeric regions . In vitro the protein binds to telomeric DNA repeats.

Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling . The structure of Tel2 consists of HEAT-like helical repeats that assemble into two separate α-solenoids . This entry represents the C-terminal solenoid which consists of eleven helices.
FPRL1/chemotaxis inhibitory protein superfamily (FLIPR/CHIP_sf)
Type: Homologous_superfamily

Formyl Peptide Receptor-Like 1 (FPRL1)-inhibitory protein (also termed FLIPr) has been shown to inhibit calcium mobilisation in neutrophils . There is evidence that FLIPr binds to FPRL1 and, at higher concentrations, to FPR , impairing the leukocyte response to FPRL1 agonists. It has revealed unknown inflammatory ligands during S.aureus infection and, as an FPRL1 antagonist, may facilitate development of therapeutic agents in FPRL1-mediated inflammatory diseases .

Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a . CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound .

CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation . By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown .

The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy . This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism . The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation . The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) .
[NiFe]-hydrogenase assembly chaperone, HybE superfamily (NiFe-hyd_HybE_sf)
Type: Homologous_superfamily

Members of this superfamily are chaperones for the assembly of [NiFe] hydrogenases, in the family of HybE, which is specific for hydrogenase-2 of Escherichia coli. Members often have an additional N-terminal rubredoxin domain .
Neuraminyllactose-binding hemagglutinin superfamily (NeuraminylLac-bd_hemagglutn_sf)
Type: Homologous_superfamily

This superfamily is comprised of several flagellar sheath adhesin proteins also called neuraminyllactose-binding haemagglutinin precursor (NLBH or HpaA) or N-acetylneuraminyllactose-binding fibrillar haemagglutinin receptor-binding subunits. NLBH is found exclusively in Helicobacter which are gut colonising bacteria and bind to sialic acid rich macromolecules present on the gastric epithelium . The sialic acid-sensitive agglutination of erythrocytes by certain strains of Helicobacter pylori has been attributed to the NLBH protein .
NADH dehydrogenase ubiquinone Fe-S protein 4-like superfamily (NDUFS4-like_sf)
Type: Homologous_superfamily

This entry includes NADH dehydrogenase [ubiquinone] iron-sulfur protein 4 (NDUS4), an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), initially identified in Neurospora crassa as a 21kDa protein . It is believed that members of this family are not involved in catalysis. This entry also includes uncharacterised bacterial sequences.
UpxZ superfamily (UpxZ_sf)
Type: Homologous_superfamily

UpxZ proteins act to inhibit transcription of heterologous capsular polysaccharide loci in Bacteroides species by interfering with the action of the UpxY family of transcription anti-terminators. As antagonists of polysaccharide locus-specific UpxY transcription anti-terminators, the UpxZ proteins exert a hierarchical level of regulation, insuring that only one of the multiple phase-variable capsular polysaccharide loci per cell characteristic of this genus is transcribed at a time .
Rtr1/RPAP2 domain superfamily (Rtr1/RPAP2_sf)
Type: Homologous_superfamily

This superfamily includes a domain found in the human RPAP2 (RNAP II associated polypeptide) protein and in the yeast Rtr1 protein . It has been suggested that this group of proteins are regulators of core RNA polymerase II function .
CCR4-NOT subunit 1, TTP binding domain superfamily (CNOT1_TTP_bind_sf)
Type: Homologous_superfamily

This entry represents the TTP binding domain of CCR4-NOT transcription complex subunit 1. It adopts a MIF4G (middle portion of eIF4G) fold .
Alkyl/aryl-sulfatase, dimerisation domain superfamily (Alkyl/aryl-sulf_dimr_sf)
Type: Homologous_superfamily

This α-helical dimerisation domain is found in alkyl/aryl-sulfatases such as the Saccharomyces cerevisiae BDS1 (

). BDS1 enables the use of SDS and 4-nitrocatechol as sulfur source .
TRAP transporter T-component superfamily (TatT_sf)
Type: Homologous_superfamily

TatT (TRAP transporter T-component) is the T-component of a sub-set of TRAP-Ts or Tripartite ATP-independent periplasmic transporters. TRAP-Ts are bacterial transport systems implicated in the import of small molecules into the cytoplasm in bacteria. They are all periplasmic lipoproteins. TatT consists of a 13-α-helical fold containing cryptic tetratricopeptide repeat motifs (cTPRs) and encompassing a pore, ie is a water-soluble trimer whose protomers are each perforated by a pore. It forms a complex with a P component, and a putative ligand-binding cleft of TatPT aligns with the pore of TatT .
MTERF superfamily, mitochondrial/chloroplastic (MTERF_sf)
Type: Homologous_superfamily

This entry represents the mitochondrial/chloroplastic transcription termination factors (MTERFs). In humans, four MTERFs have been identified (MTERF1-4). MTERF1 was first identified as a factor responsible for terminating heavy strand transcription at a specific site at the leu-tRNA, thereby modulating the ratio of mitochondrial ribosomal RNA to mRNA . Later, MTERF1 was found to stimulate transcriptional initiation and appeared to be in the control of mitochondrial replication pausing . From a structural study, it binds to dsDNA containing the termination sequence and unwinds the DNA molecule, promoting base eversion, which is critical for transcription termination .
Anti-lipopolysaccharide factor/Scygonadin superfamily (Anti-LPS_factor/Scygonadin_sf)
Type: Homologous_superfamily

Anti-lipopolysaccharide factor binds to bacterial LPS and may specifically inhibit the LPS-mediated activation of the hemolymph coagulation. It has a strong antibacterial effect, especially on the growth of Gram-negative bacteria . This entry also includes the antibacterial protein Scygonadin, which has antibacterial activity against the Gram-positive bacterium Micrococcus luteus .
Pathogenicity island protein gp6 superfamily (SAPIS-gp6_sf)
Type: Homologous_superfamily

Gp6, a Staphylococcus aureus pathogenicity island 1 protein, is a mobile genetic element that carries genes for several superantigen toxins. It is a dimeric protein produced from the pathogenicity island with a helix-loop-helix motif similar to that of bacteriophage scaffolding proteins. It is thought to determine the size of the capsids of distribution of the SAPI1 genome as it acts as an internal scaffolding protein during capsid size determination .
Spidroin, C-terminal domain superfamily (Spidroin_C_sf)
Type: Homologous_superfamily

Spidroin is spider dragline silk. It is composed of two proteins, major ampullate spidroin 1 (MaSp1) and major ampullate spidroin 2 (MaSp2) . MaSp1 contains five α-helices . Spidroins contain repetitive units capped between non-repetitive N-terminal and C-terminal domains, whose composition varies among species and thus determines the variety of mechanical properties of spider silks. The C-terminal domains are conserved among spider silk proteins .

This superfamily represents the C-terminal domain of spidroin.
Churchill superfamily (Churchill_sf)
Type: Homologous_superfamily

This superfamily consists of several eukaryotic Churchill proteins. This protein contains a novel zinc binding region that mediates FGF signalling during neural development. The slow induction by FGF of a transcription factor (Churchill) in the neural plate in turn induces expression of Sip1 (Smad interacting protein-1), which inhibits mesodermal genes and sensitizes cells to later neural inducing factors .
ACP, N-terminal domain superfamily (ACP_N_sf)
Type: Homologous_superfamily

The alpha C protein (ACP) is found in Streptococcus and acts as an invasin which plays a role in the internalisation and translocation of the organism across human epithelial surfaces. Group B Streptococcus is the leading cause of diseases including bacterial pneumonia, sepsis and meningitis. The N-terminal of ACP is associated with virulence and forms a β sandwich and a three helix bundle .
DBF-type zinc finger superfamily (Znf_DBF_sf)
Type: Homologous_superfamily

In eukaryotes, initiation of DNA replication requires the assembly of pre-replication complexes (pre-RCs) on chromatin during the G1 phase. In the S phase, pre-RCs are activated by two protein kinases, Cdk2 and Cdc7, which results in the loading of replication factors and the unwinding of replication origins by the MCM helicase complex . Cdc7 is a serine/threonine kinase that is conserved from yeast to human. It is regulated by its association with a regulatory subunit, the Dbf4 protein. This complex is often referred to as DDK (Dbf4-dependent kinase) .

DBF4 contains an N-terminal BRCT domain and a C-terminal conserved region that could potentially coordinate one zinc atom, the DBF4-type zinc finger. This entry represents the zinc finger, which is important for the interaction with Cdc7 .
Hen1, N-terminal domain superfamily (Hen1_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal domain of the bacterial Hen1 protein, which is a 3' terminal RNA ribose 2'-O-methyltransferase that is involved in bacterial RNA repair . Hen1 forms a heterotetramer with Pnkp. The heterotetramer has been shown to repair transfer RNAs cleaved by ribotoxins in vitro . The N-terminal domain of Hen1 contributes to the ligase activity of the heterotetramer.
CBP/p300, atypical RING domain superfamily (RING_CBP-p300_sf)
Type: Homologous_superfamily

CBP (CREB-binding protein) and p300 (also known as CREBBP or KAT3A and EP300 or KAT3B, respectively) are two histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. The catalytic core of animal CBP-p300 contains a bromodomain, a CH2 region containing a discontinuous PHD domain interrupted by this RING domain, and a HAT domain. Bromodomain-RING-PHD forms a compact module in which the RING domain is juxtaposed with the HAT substrate-binding site. This ring domain contains only a single zinc ion-binding cluster instead of two; instead of a second zinc atom, a network of hydrophobic interactions stabilizes the domain. The RING domain has an inhibitory role. Disease mutations that disrupt RING attachment lead to upregulation of HAT activity. HAT regulation may require repositioning of the RING domain to facilitate access to an otherwise partially occluded HAT active site. Plant CBP-p300 type HATs lack a bromodomain whose role in the animal animal CBP-p300's is to bind acetylated histones; it has been suggested that these plant proteins may utilize a different domain or another bromodomain protein to perform this function .
Stage V sporulation protein AA, N-terminal domain superfamily (SporV_AA_N_sf)
Type: Homologous_superfamily

This domain superfamily is found in bacteria - primarily Firmicutes, and is approximately 90 amino acids in length. There is a single completely conserved residue G that may be functionally important. Most annotation associated with this domain suggests that it is involved in the fifth stage of sporulation, however there is little publication to back this up.
SeBP-like superfamily (SeBP-like_sf)
Type: Homologous_superfamily

Selenium is an important nutrient which needs to be regulated since lack of the nutrient leads to cell abnormalities and high concentrations are toxic. The selenium binding protein (SeBP) regulates the level of free selenium in the cell by sequestering the nutrient during transport. SeBP acts as a pentamer and delivers the selenium to the selenophosphate synthetase enzyme . Each subunit is composed of an α helix on top of a four stranded twisted ss sheet, stabilised by hydrogen bonds . Proteins in this entry are restricted to the archaeal Methanococcales.