SII-SWORD/CoKE huggingface dataset:
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaE (Prd_NiFe_hyd_3_EhaE)
Type: Family

[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster .

Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family . Members of this subgroup include:

Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coli

CO-induced hydrogenase (Coo) from Rhodospirillum rubrum

Mbh hydrogenase from Pyrococcus furiosus

Eha and Ehb hydrogenases from Methanothermobacter species

Ech hydrogenase from Methanosarcina barkeri

Energy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe] hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe] hydrogenases function as ion pumps.

Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S] polyferredoxin, ten other predicted integral membrane proteins (EhaA

, EhaB

, EhaC

, EhaD

, EhaE

, EhaF

, EhaG

, EhaI

, EhaK

, EhaL

and

) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) . The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.

Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar
eha
operon structure.

This entry represents small membrane proteins that are predicted to be the EhaE transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaI (Prd_NiFe_hyd_3_EhaI)
Type: Family

[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster .

Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family . Members of this subgroup include:

Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coli

CO-induced hydrogenase (Coo) from Rhodospirillum rubrum

Mbh hydrogenase from Pyrococcus furiosus

Eha and Ehb hydrogenases from Methanothermobacter species

Ech hydrogenase from Methanosarcina barkeri

Energy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe] hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe] hydrogenases function as ion pumps.

Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S] polyferredoxin, ten other predicted integral membrane proteins (EhaA

, EhaB

, EhaC

, EhaD

, EhaE

, EhaF

, EhaG

, EhaI

, EhaK

, EhaL

and

) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) . The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.

Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar
eha
operon structure.

This entry represents small membrane proteins that are predicted to be the EhaI transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaK (Prd_NiFe_hyd_3_EhaK)
Type: Family

[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe] hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S] cluster .

Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family . Members of this subgroup include:

Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coli

CO-induced hydrogenase (Coo) from Rhodospirillum rubrum

Mbh hydrogenase from Pyrococcus furiosus

Eha and Ehb hydrogenases from Methanothermobacter species

Ech hydrogenase from Methanosarcina barkeri

Energy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe] hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe] hydrogenases function as ion pumps.

Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S] polyferredoxin, ten other predicted integral membrane proteins (EhaA

, EhaB

, EhaC

, EhaD

, EhaE

, EhaF

, EhaG

, EhaI

, EhaK

, EhaL

and

) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) . The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.

Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar
eha
operon structure.

This entry represents small membrane proteins that are predicted to be the EhaK transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Ribonuclease H1, N-terminal (RNase_H1_N)
Type: Domain

This entry represents the N-terminal domain of RNase HI, which has a 3-layer α/β/α structure . This domain is lacking in retroviral and prokaryotic enzymes, but shows a striking structural similarity to the ribosomal protein L9 N-terminal domain, and may function as a regulatory RNA-binding module. However, the topology of this domain differs from structures of known RNA binding domains such as the double-stranded RNA binding domain (dsRBD), the hnRNP K homology (KH) domain and the RNP motif. Eukaryotic RNases HI possess either one or two copies of this small N-terminal domain, in addition to the well-conserved catalytic RNase H domain. RNase HI belongs to the family of ribonuclease H enzymes that recognise RNA:DNA hybrids and degrade the RNA component.
Nitrogen regulatory PII-like, alpha/beta (N-reg_PII-like_a/b)
Type: Homologous_superfamily

This superfamily represents a structural domain found in the nitrogen regulatory protein PII, in ATP phosphribosyltransferases (C-terminal domain), in the divalent ion tolerance protein CutA1, and in some bacterial hypothetical proteins. This domain consists of a ferredoxin-like α/β sandwich, which forms trimeric structures with orthogonally packed β-sheets around a three-fold axis.
Mss4/translationally controlled tumour-associated TCTP (Mss4/transl-control_tumour)
Type: Homologous_superfamily

This superfamily represents a structural domain with a complex fold consisting of several coiled β-sheets. This domain exists as a duplication, consisting of a tandem repeat of two similar structural motifs. This entry represents copies of this structural motif in the following protein families:

Mss4, which contains a zinc-binding site.

Translationally controlled tumour-associated protein TCTP, which contains an insertion of an α-helix hairpin, and which lacks a zinc-binding site.

Mss4 is a conserved accessory factor for Rab GTPases, which function as ubiquitous regulators of intracellular membrane trafficking . Mss4 acts to promote nucleotide release from exocytic but not endocytic Rab GTPases. Mss4 has a complex fold made of several coiled β-sheets, and consists of a duplication of tandem repeats of two similar structural motifs. It contains a zinc-binding site.

Other proteins that show structural similarity to Mss4 include the translationally controlled tumour-associated proteins TCTPs, which contain an insertion of an α helical hairpin, and lack the zinc-binding site. TCTPs are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and the human acute allergic response .
Cytotoxic necrotizing factor-like, catalytic (Cytotoxic_necrot_fac-like_cat)
Type: Homologous_superfamily

This entry represents the catalytic domain from several bacterial cytotoxic necrotizing factor proteins and the related dermonecrotic toxin (DNT) from Bordetella species. Cytotoxic necrotizing factor 1 (CNF1) is a toxin which in Escherichia coli forms a 4-layer α/β/β/α structure containing mixed β-sheets . CNF1 is expressed in strains of E. coli causing uropathogenic and neonatal meningitis. It alters the host cell actin cytoskeleton and promotes bacterial invasion of the blood-brain barrier endothelial cells . CNF1 belongs to a unique group of large cytotoxins that cause constitutive activation of Rho guanosine triphosphatases (GTPases), which are key regulators of the actin cytoskeleton .

Bordetella dermonecrotic toxin (DNT) stimulates the assembly of actin stress fibres and focal adhesions by deamidating or polyaminating Gln63 of the small GTPase Rho. DNT is an A-B toxin composed of an N-terminal receptor-binding (B) domain and a C-terminal enzymatically active (A) domain .

A similar structural motif can be found in several hypothetical proteins, including YfiH from Shigella flexneri , YlmD from Bacillus stearothermophilus, NMB0706 from Neisseria meningitidis serogroup B and CC0490 from Caulobacter crescentus.
Killer toxin, SMK, beta subunit (Killer_tox_SMK_b)
Type: Domain

This entry represents the beta subunit of SMK killer toxins that are secreted by several strains of yeasts. SMK toxin is encoded by a single open reading frame of chromosomal DNA (the SMK1 gene) and is translated in the form of a 222 amino acid preprotoxin. This preprotoxin is converted to the alpha and beta heterodimeric mature toxin, with a molecular weight of 14 kDa, through stepwise proteolytic processing.

The killer toxin SMK (salt-mediated killer) from the halotolerant yeast Pichia farinosa acts to kill sensitive strains of yeast. SMK exhibits maximum activity under conditions of acidic pH and high salt concentration. It is composed of two distinct subunits, alpha and beta, which tightly interact with each other under acidic conditions, jointly folding into an ellipsoidal single domain structure belonging to the α/β-sandwich family. SMK assumes a similar folding topology to the fungal killer toxin KP4, forming two left-handed split β/α/β motifs, which is rarely found in other toxins; hence, these toxins may be evolutionarily or functionally related . SMK appears to function by associating with the membranes of sensitive cells .
Salt-mediated killer toxin, alpha subunit (SMK_a)
Type: Homologous_superfamily

The killer toxin SMK (salt-mediated killer) from the halotolerant yeast Pichia farinosa acts to kill sensitive strains of yeast. SMK exhibits maximum activity under conditions of acidic pH and high salt concentration. It is composed of two distinct subunits, alpha and beta, which tightly interact with each other under acidic conditions, jointly folding into an ellipsoidal single domain structure belonging to the α/β-sandwich family. SMK assumes a similar folding topology to the fungal killer toxin KP4, forming two left-handed split β/α/β motifs, which is rarely found in other toxins; hence, these toxins may be evolutionarily or functionally related . SMK appears to function by associating with the membranes of sensitive cells .
Killer toxin Kp4/SMK (Killer_tox_Kp4/SMK)
Type: Homologous_superfamily

This superfamily represents a structural fold found in the killer toxins Kp4 and SMK, consisting of two left-handed split β/αβ motifs, which is rarely found in other toxins; hence, these toxins may be evolutionarily or functionally related . Killer toxins are polypeptides secreted by some fungal species that kill sensitive cells of the same or related species, often functioning by creating pores in target cell membranes.

The fungal killer toxin KP4 from the corn smut fungus, Ustilago maydis (Smut fungus), is encoded by a resident symbiotic double-stranded RNA virus, Ustilago maydis P4 virus (UmV4), within fungal cells. Unlike most killer toxins, KP4 is a single polypeptide . KP4 inhibits voltage-gated calcium channels in mammalian cells, which in turn inhibits cell growth and division by blocking calcium import. KP4 adopts a structure consisting of a two-layer α/β sandwich with a left-handed crossover .
Glycoside hydrolase/deacetylase, beta/alpha-barrel (Glyco_hydro/deAcase_b/a-brl)
Type: Homologous_superfamily

This superfamily represents a structural domain found in glycoside hydrolase families 38 (

, e.g. alpha-mannosidase) and 57 (

, e.g. 4-alpha-glucanotransferase, N-terminal) , as well as in NodB-like polysaccharide deacetylase and in some hypothetical proteins (e.g. TT1467, N-terminal domain). This domain consists of a 7-stranded β/α barrel, although in some families the β-barrels may be distorted and may vary in the number of strands.
Large ribosomal subunit protein eL37/eL43 (Ribosomal_eL37/eL43)
Type: Homologous_superfamily

This superfamily represents the core domain of the large ribosomal subunit protein eL37/eL43 from archaea and eukaryotes, which where previously known as ribosomal proteins L37ae and L37e. Members of this group share a common rubredoxin-like metal-binding fold containing two CX(n)C motifs (where n is usually two) .
Zinc-binding ribosomal protein (Ribosomal_zn-bd)
Type: Homologous_superfamily

This superfamily represents a rubredoxin-like metal-binding fold found in bL32, bL33, eL37, eL43, eL40, eL42 and other ribosomal proteins. This domain contains two CX(n)C motifs (where n is usually two) .
SKP1/BTB/POZ domain superfamily (SKP1/BTB/POZ_sf)
Type: Homologous_superfamily

The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is a versatile protein-protein interaction motif involved in many cellular functions, including transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and targeting proteins for ubiquitination . The BTB domain can occur alongside other domains: BTB-zinc finger (BTB-ZF), BTB-BACK-Kelch (BBK), voltage-gated potassium channel T1 (T1-Kv) , MATH-BTB, BTB-NPH3 and BTB-BACK-PHR (BBP). Other proteins, such as Skp1 and ElonginC, consist almost exclusively of the core BTB fold. In all of these protein families, the BTB core fold is structurally conserved, consisting of a 2-layer α/β topology where a cluster of α-helices is flanked by short β-sheets . POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT . The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

This entry includes the BTB/POZ domain, as well as Skp1 N-terminal region which has an α/β structure similar to that of the BTB/POZ domain fold .
UDP-3-O-acyl N-acetylglucosamine deacetylase, C-terminal (UDP-acyl_GlcNac_deAcase_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain.

UDP-3-O-N-acetylglucosamine deacetylases are zinc-dependent metalloamidases that catalyse the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram-negative bacteria. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds . The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer α/β structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid . This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents .
Restriction endonuclease type II-like (Restrct_endonuc-II-like)
Type: Homologous_superfamily

This superfamily represents the core structure found in most type II restriction endonucleases, consisting of a 3-layer α/β/α topology with mixed β-sheets. This core structure can be found in the restriction endonucleases EcoRI, EcoRV, BamHI, BglI, BglII, BstyI, PvuII, MunI, NseI, NgoIV, BsobI, HincII, MspI, FokI (C-terminal), EcoO109IR, as well as in lamba exonuclease, DNA mismatch repair protein MutH, VSR (very short repair) endonucleases, TnsA endonucleases (N-terminal), endonucleases I (Holliday junction resolvase), Hjc-like enzymes, XPF/Rad1/Mus81 nucleases, RecB and RecC exodeoxyribonuclease V (C-terminal), and RecU-like enzymes.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .
Restriction endonuclease, type II, EcoRI/MunI (Restrct_endonuc_II_EcoRI/MunI)
Type: Homologous_superfamily

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This entry represents restriction endonucleases EcoRI and MunI, which are closely related in sequence. EcoRI requires magnesium as a cofactor, while MunI does not. EcoRI recognises the DNA sequence GAATTC and cleaves after G-1 , while MunI recognises the palindromic hexanucleotide sequence CAATTG and cleaves after C-1 .