SII-SWORD/CoKE huggingface dataset:
His-Me finger superfamily (His-Me_finger_sf)
Type: Homologous_superfamily

His-Me finger is a diverse superfamily of endonuclease proteins present in all forms of life and involved in various cellular processes. The structural core of this group of proteins consists of a β-hairpin followed by an α-helix, forming a binding site for a single catalytic metal ion. The His-Me finger is thought to be suited for efficient, nonspecific DNA cleavage. The term 'His-Me' refers to a nearly invariant catalytic histidine (His) residue and a bound metal ion (Me). His-Me finger-containing proteins are commonly called HNH nucleases. HNH sequence motif consists of the central, nearly invariant, catalytic histidine at the C terminus of the first β-strand (HNH), an asparagine (HNH) in the extensive loop connecting the two β-strands known as the ω-loop (16)-and a histidine (HNH) in the core α-helix. This second histidine is often substituted by an asparagine, which, in most cases, is the only residue that directly binds the metal ion .
RGS, subdomain 2 (RGS_subdomain_2)
Type: Homologous_superfamily

RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins . Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. Usually, the response is terminated upon GTP hydrolysis by the alpha subunit (

), which can then bind the beta-gamma dimer (

,

) and the receptor. However, in some cases, RGS proteins can have a positive effect on signal potentiation .

All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality . RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (

), PDZ for binding to GPCRs (

), PTB for phosphotyrosine-binding (

), RBD for Ras-binding (

), GoLoco for guanine nucleotide inhibitor activity (

), PX for phosphatidylinositol-binding (

), PXA that is associated with PX (

), PH for stimulating guanine nucleotide exchange (

), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (

) . Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.

The RSG box in RSG4 corresponds to an array of α-helices that fold into two domains. Both are required for GAP (GTPase activating protein) activity . This superfamily represents the subdomain 2 of the RSG box.
Type VII secretion system protein EssD-like (Endonuclea_NS_2)
Type: Domain

This entry includes EssD, which is a component of the type VII secretion system (Ess) and acts as a secretion factor for the Ess pathway in Staphylococcus aureus . Proteins containing this domain are part of the DNA/RNA non-specific endonuclease family that contains the His-Me finger fold, which is thought to be suited for efficient, nonspecific DNA cleavage .
Secreted effector protein SifA, C-terminal domain superfamily (SifA_C_sf)
Type: Homologous_superfamily

Salmonella typhimurium SifA is an effector protein that alters host cell physiology and promotes bacterial survival in host tissues. This protein is a member of the WxxxE family of bacterial TTSS effectors that mimic activated small GTPases and it is required for endosomal tubulation and formation of Salmonella-induced filaments (Sifs), which are filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Sif formation is concomitant with intracellular bacterial replication .

This superfamily represents the C-terminal WxxxE-containing domain which is organised in two three-helix bundles that form a V-shaped structure. The WxxxE conserved sequence important for both the folding and the secretion of the SifA effector . This domain also includes a six-residue prenylation motif which influences the membrane association and targeting properties of SifA .
DNA/RNA non-specific endonuclease superfamily (DNA/RNA_non-sp_Endonuclease_sf)
Type: Homologous_superfamily

A superfamily of bacterial and eukaryotic endonucleases

share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. A histidine has been shown to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.
Homing endonuclease, His-Me finger superfamily (Homing_endonuclease_His-Me)
Type: Homologous_superfamily

This superfamily represents the His-Me finger found in homing endonuclease, such as I-Ppo from Physarum polycephalum. I-Ppo is a homing endonuclease that bends its DNA target, resulting in significant deformations of the minor and major groove near the scissile phosphate groups .

His-Me finger is a diverse superfamily of endonuclease proteins present in all forms of life and involved in various cellular processes. The structural core of this group of proteins consists of a β-hairpin followed by an α-helix, forming a binding site for a single catalytic metal ion. The His-Me finger is thought to be suited for efficient, nonspecific DNA cleavage. The term 'His-Me' refers to a nearly invariant catalytic histidine (His) residue and a bound metal ion (Me). His-Me finger-containing proteins are commonly called HNH nucleases. HNH sequence motif consists of the central, nearly invariant, catalytic histidine at the C terminus of the first β-strand (HNH), an asparagine (HNH) in the extensive loop connecting the two β-strands known as the ω-loop (16)-and a histidine (HNH) in the core α-helix. This second histidine is often substituted by an asparagine, which, in most cases, is the only residue that directly binds the metal ion .
Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment superfamily (PfEMP1_ATS_sf)
Type: Homologous_superfamily

ATS is the intracellular and relatively conserved acidic terminal segment of the Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) . This domain appears to be present in all variants of the highly polymorphic PfEMP1 proteins.
Diaphanous, GTPase-binding domain superfamily (DIA_GBD_sf)
Type: Homologous_superfamily

This superfamily contains the N-terminal domain of diaphanous, a subclass of formins whose members are regulated by the binding of a small GTP-binding protein of the Rho subfamily. These proteins are characterised by a variety of shared domains: an N-terminal GTPase-binding domain (GBD), formin-homology domains FH1, FH2 and FH3, and a C-terminal conserved Dia-autoregulatory domain (DAD) that binds the GBD. This N-terminal domain corresponds to the GBD, a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members. Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton .
Peptidase C10, streptopain superfmaily (Streptopain_sf)
Type: Homologous_superfamily

This entry represents streptopain (or SpeB), a highly conserved secreted cysteine protease that is found in the majority of S. pyogenes strains. Production, secretion, and activation of SpeB is highly regulated, and its proteolytic activity has been linked to immunomodulating activities during infection . The substrates for the enzyme have been extensively investigated, and during infection, SpeB demonstrates a broad substrate tolerance and, in an attempt to circumvent the immune system, degrades a multitude of proteins, such as interleukins, immunoglobulins, integrins and antimicrobial peptides. SpeB belongs to clan CA (of the MEROPS database) and therefore exhibits a papain-like fold .
Domain of unknown function DUF5086 superfamily (DUF5086_sf)
Type: Homologous_superfamily

This is a superfamily of uncharacterised proteins from Proteobacteria.
Alphavirus nsP2 protease domain superfamily (Alphavirus_nsp2pro_sf)
Type: Homologous_superfamily

The superfamily of alphaviruses includes 26 known members. They infect a variety of hosts including mosquitoes, birds, rodents and other mammals with worldwide distribution. Alphaviruses also pose a potential threat to human health in many areas. For example, Venezuelan Equine Encephalitis Virus (VEEV) causes encephalitis in humans as well as livestock in Central and South America, and some variants of Sinbis Virus (SIN) and Semliki Forest Virus (SFV) have been found to cause fever and arthritis in humans .

Alphaviruses possess a single-stranded RNA genome of approximately 12 kb. The genomic RNA of alphaviruses is translated into two polyproteins that, respectively, encode structural proteins and nonstructural proteins. The nonstructural proteins may be translated as one or two polyproteins, nsp123 or nsp1234, depending on the virus. These polyproteins are cleaved to generate nsp1, nsp2, nsp3 and nsp4 by a protease activity that resides within nsp2. The nsp2 protein of alphaviruses has multiple enzymatic activities. Its N-terminal domain has been shown to possess ATPase and GTPase activity, RNA helicase activity and RNA 5'-triphosphatase activity. The C-terminal nsp2pro domain of nsp2 is responsible for the regulation of 26S subgenome RNA synthesis, switching between negative- and positive-strand RNA synthesis, targeting nsp2 for nuclear transport and proteolytic processing of the nonstructural polyprotein . The nsp2pro domain is a member of peptidase family C9 of clan CA.

The nsp2pro domain consists of two distinct subdomains. The nsp2pro N-terminal subdomain is largely α-helical and contains the catalytic dyad cysteine and histidine residues organised in a protein fold that differs significantly from any known cysteine protease or protein folds.
The nsp2pro C-terminal subdomain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases and provides essential elements that contribute to substrate recognition and may also regulate the structure of the substrate binding cleft .

This domain covers the entire nsp2pro domain.
Mu1 membrane penetration protein, domain III (Mu1_membr_pen_domIII)
Type: Homologous_superfamily

Mu1 is an outer capsid protein that acts as a reoviral penetration agent. Non-enveloped animal reoviruses must enter host cells by membrane penetration that does not involve membrane fusion, as they lack a viral membrane. Reoviruses are activated by proteolytic cleavage in the intestinal lumen, leading to infectious subviral particles. The core of the virus is coated by a layer of mu1 and sigma3 proteins. Proteases strip off sigma3 exposing mu1, which provides the membrane penetration machinery that perforates the membrane. In addition, N-terminal myristoylation of polypeptide Mu1 are required for site-specific cleavage to Mu1C in transfected cells . Mu1 forms a trimer, where the three mu1 molecules are coiled around one another with a right-handed twist. The mu1 chain folds into four distinct domains: three intertwined, predominantly α helical domains and a jelly-roll β-sandwich .
Enhancer of mRNA-decapping protein 4, conserved C-terminal domain superfamily (EDC4_C_sf)
Type: Homologous_superfamily

This superfamily represents the highly conserved C-terminal region of Enhancer of mRNA-decapping protein 4 (EDC4, also known as Ge-1) which adopts an all α-helical fold . This domain is necessary and sufficient for P-body targeting and, in plants, it also mediates DCP1 and DCP2 interaction, as well as self-association .
Ethanolamine ammonia-lyase heavy chain, domain 2 (EutB_dom_2_sf)
Type: Homologous_superfamily

This superfamily represents an α-helical N-terminal subdomain found in several bacterial ethanolamine ammonia-lyase heavy chain (EutB) (also known as ethanolamine ammonia lyase large subunit and ethanolamine ammonia-lyase alpha subunit) proteins. Ethanolamine ammonia-lyase is a bacterial enzyme that catalyses the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia. The enzyme consists of EutB and EutC (beta-subunit) subunits which form a trimer composed of the (α-β)2 dimer .
Nitric oxide synthase, domain 2 superfamily (NOS_dom_2)
Type: Homologous_superfamily

In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS . This domain can also be found in bacterial NOS that only has the oxygenase domain.

Nitric oxide synthase (

) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed .

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria . Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (

). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation . The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain . Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain.
Ethanolamine ammonia-lyase heavy chain, N-terminal domain (EutB_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in several bacterial ethanolamine ammonia-lyase heavy chain (EutB) (also known as ethanolamine ammonia lyase large subunit and ethanolamine ammonia-lyase alpha subunit) proteins. Ethanolamine ammonia-lyase is a bacterial enzyme that catalyses the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia. The enzyme consists of EutB and EutC (beta-subunit) subunits which form a trimer composed of the (α-β)2 dimer .
Adenovirus Pll, hexon, subdomain 2 (Adenovirus_Pll_hexon_sub2)
Type: Homologous_superfamily

This entry represents a structural subdomain with a complex α/β topology.

Hexon is a major coat protein found in various species-specific Adenoviruses, which are type II dsDNA viruses. Hexon coat proteins are synthesised during late infection and form homo-trimers. The 240 copies of the hexon trimer that are produced are organised so that 12 lie on each of the 20 facets. The central 9 hexons in a facet are cemented together by 12 copies of polypeptide IX. The penton complex, formed by the peripentonal hexons and base hexon (holding in place a fibre), lie at each of the 12 vertices . The hexon coat protein is a duplication consisting of two domains with a similar fold packed together like the nucleoplasmin subunits. Within a hexon trimer, 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; each domain is heavily decorated with many insertions .
Nitric oxide synthase, domain 1 superfamily (NOS_dom_1)
Type: Homologous_superfamily

In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS . This domain can also be found in bacterial NOS that only has the oxygenase domain.

Nitric oxide synthase (

) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed .

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria . Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (

). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation . The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain . Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain.
Nitric oxide synthase, domain 3 superfamily (NOS_dom_3)
Type: Homologous_superfamily

In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS . This domain can also be found in bacterial NOS that only has the oxygenase domain.

Nitric oxide synthase (

) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed .

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria . Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (

). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation . The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain . Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain.
FokI, recognition domain, subdomain 1 and 2 (FokI_dom_1_2)
Type: Homologous_superfamily

Type IIS restriction endonuclease FokI (

) is a member of an unusual class of bipartite restriction enzymes that recognises the double-stranded DNA sequence 5'-GGATG-3' and cleave DNA phosphodiester groups 9 base pairs away on this strand and 13 base pairs away on the complementary strand . FokI contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively.

The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP .

This superfamily covers the domain 1 and 2 (D1 and D2) found in type-2 restriction enzyme FokI. D1 and D2 make almost all of the base-specific contacts with the DNA .
Type I restriction modification DNA specificity domain superfamily (Restrct_endonuc_typeI_TRD_sf)
Type: Homologous_superfamily

This domain superfamily is also known as the target recognition domain (TRD). Restriction-modification (R-M) systems protect a bacterial cell against invasion of foreign DNA by endonucleolytic cleavage of DNA that lacks a site specific modification. The host genome is protected from cleavage by methylation of specific nucleotides in the target sites. In type I systems, both restriction and modification activities are present in one heteromeric enzyme complex composed of one DNA specificity subunit (this entry), two modification (M) subunits and two restriction (R) subunits .
Bacteriophage T4, Gp32, single-stranded DNA-binding superfamily (Phage_T4_Gp32_ssDNA-bd_sf)
Type: Homologous_superfamily

This superfamily is represented by the Bacteriophage T4, Gp32, single-stranded DNA-binding protein. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

Single-stranded DNA-binding protein (also known as Gp32 or SSB) is essential for bacteriophage T4 DNA replication, recombination and repair, acting to stimulate replisome processing and accuracy through its binding to ssDNA as the replication fork advances . The crystal structure of Gp32 shows an ssDNA binding cleft comprised of regions from three structural subdomains, through which ssDNA can slide freely . The structure of Gp32 is similar to other phage ssDNA-binding proteins such as Gp2.5 from bacteriophage T4, and gene V protein, both of which have a nucleic acid-binding OB-type fold. However, Gp32 contains a zinc-finger subdomain at residues 63-111 that is not found in the other two phage proteins.

This protein stimulates the activities of viral DNA polymerase and DnaB-like SF4 replicative helicase, probably via its interaction with the helicase assembly factor , and together with DnaB-like SF4 replicative helicase and the helicase assembly factor, promotes pairing of two homologous DNA molecules containing complementary single-stranded regions and mediates homologous DNA strand exchange .