SII-SWORD/CoKE huggingface dataset:
Methyl-coenzyme M reductase, alpha subunit, N-terminal (Me_CoM_Rdtase_asu_N)
Type: Domain

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This entry represents the N-terminal domain of the alpha subunit, which has a ferredoxin-like α/β-sandwich fold with a duplicated β-α-β topology.
Viral chemokine binding protein (Orthopox_35kDa)
Type: Family

This entry represents a family of proteins from poxviruses, including Protein OPG170 from Vaccinia virus (also known as A41) and Protein T1 from Rabbit fibroma virus. These secreted proteins interact with members of both the CC and CXC superfamilies of chemokines . It has been suggested that these secreted proteins modulate leukocyte influx into virus-infected tissues .
Proteasome activator PA28, N-terminal domain (Proteasome_activ_PA28_N)
Type: Domain

The specificity of the 20S proteasome, which degrades many intracellular proteins, is regulated by protein complexes that bind to one or both ends of the cylindrical proteasome structure. Proteasome activator 28 (PA28), also known as 11S regulator or REG, is one of these complexes. PA28 binds to the 20S proteasome and stimulates peptidase activity in and ATP-independent manner.

Three PA28 subunits that have been identified, PA28alpha, PA28beta and PA28gamma (also known as the Ki antigen), which share extensive sequence similarity, apart from a highly variable internal segment . PA28alpha and PA28beta form a ring shaped hexameric structure of alternating alpha and beta subunits. The catalytic properties of PA28alpha and PA28beta-activated proteosome are similar .

This entry represents a single α-helix N-terminal domain found in the proteasome activator 28 subunits.
Proteasome activator PA28, C-terminal domain (PA28_C)
Type: Domain

The specificity of the 20S proteasome, which degrades many intracellular proteins, is regulated by protein complexes that bind to one or both ends of the cylindrical proteasome structure. Proteasome activator 28 (PA28), also known as 11S regulator or REG, is one of these complexes. PA28 binds to the 20S proteasome and stimulates peptidase activity in and ATP-independent manner.

This entry represents the C-terminal domain found in the proteasome activator 28 subunits.
Phospholipase A1 (PLipase_A1)
Type: Family

Outer membrane phospholipase A (OMPLA) is an integral membrane phospholipase, which is present in many Gram-negative bacteria and has a broad substrate specificity

. The role of OMPLA has been most thoroughly studied in Escherichia coli,
where it participates in the secretion of bacteriocins. Bacteriocin release is triggered by a lysis protein (bacteriocin release protein or BRP), followed by a phospholipase dependent accumulation of lysophospholipids and free fatty acids in the outer membrane . The reaction products enhance the permeability of the outer membrane, which allows the semispecific secretion of bacteriocins. One speculative function of OMPLA is related to organic solvent tolerance in bacteria.
Phosphotransferase system, lactose/cellobiose-type IIA subunit (PTS_IIA_lac/cel)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The lactose/cellobiose-specific family are one of four structurally and functionally distinct group IIA PTS system enzymes. This family of proteins normally function as a homotrimer, stabilised by a centrally located metal ion . Separation into subunits is thought to occur after phosphorylation.
Shiga-like toxin, beta subunit (SLT_beta)
Type: Family

This family represents the B subunit of shiga-like toxin (SLT or verotoxin) produced by some strains of Escherichia coli associated with hemorrhagic colitis and hemolytic uremic syndrome. SLT s are composed of one enzymatic A subunit and five cell binding B subunits .
Aspartate decarboxylase (Asp_decarbox)
Type: Family

Decarboxylation of aspartate is the major route of beta-alanine production in bacteria, and is catalysed by the enzyme L-aspartate decarboxylase (ADC,

). Beta-alanine is required for the biosynthesis of pantothenate, in which the enzyme plays a critical regulatory role. The enzyme is translated as an inactive proenzyme , and is cleaved via self-processing at Gly23-Ser24 to yield an alpha chain (C-terminal fragment) and beta chain (N-terminal fragment). This model spans the precursor (or both beta and alpha chains) of aspartate decarboxylase. A pyruvoyl cofactor, which is covalently bound to the enzyme, is required for activity. The active site of the tetrameric enzyme is located at the interface of two subunits, with a lysine and a histidine from the beta chain of one subunit forming the active site with residues from the alpha chain of the adjacent subunit .
Guanylate-binding protein/Atlastin, C-terminal (Guanylate-bd/ATL_C)
Type: Domain

Guanylate-binding protein is a GTPase that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups: the small 47-kd GTPases, the Mx proteins, and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class. In humans, there are seven GBPs (hGBP1-7) . Structurally, hGBP1 consists of two domains: a compact globular N-terminal domain harbouring the GTPase function (

), and an α-helical finger-like C-terminal domain. Human GBP1 is secreted from cells without the need of a leader peptide, and has been shown to exhibit antiviral activity against Vesicular stomatitis virus and Encephalomyocarditis virus, as well as being able to regulate the inhibition of proliferation and invasion of endothelial cells in response to IFN-gamma .

This entry represents the C-terminal domain of the guanylate-binding protein. Proteins containing this domain also include Atlastin2/3. They are GTPases tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes .
Porin, LamB-type (Porin_LamB)
Type: Family

Maltoporin (LamB protein) forms a trimeric structure which facilitates the diffusion of maltodextrins across the outer membrane of Gram-negative bacteria. The membrane channel is formed by an antiparallel β-barrel . Loop 3 folds into the core to constrict pore size. Long irregular loops are found on the extracelllular side, while short turns are in the periplasm. Tightly-bound water molecules are found in the eyelet of the passage, and only substrates that can displace and replace the broken hydrogen bonds are likely to enter the pore. Loops 4, 6, and 9 have the greatest mobility and are highly variable; these are postulated to attract maltodextrins .

The porin LamB family also includes porin BglH, which may be a sugar porin with a broad carbohydrate specificity, and sucrose porin .
ADP-ribosyl cyclase (CD38/157) (ADP-ribosyl_cyclase)
Type: Family

CD38, the HUGO gene name, is also called T10 or ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (

). CD38 is a novel enzyme capable of catalysing multiple reactions, including NAD glycohydrolase, ADP-ribosyl cyclase, cyclic ADP ribose hydrolase and base-exchange activities. Two of the enzymatic products, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), are calcium messengers in a wide variety of cells from protist, plant, and mammal to human. CD38 is a positive and negative regulator of cell activation and proliferation, depending on the cellular environment. It is involved in adhesion between human lymphocytes and endothelial cells and is involved in the metabolism of two calcium messengers, cADPR and NAADP.

CD157 (also called BP-3/IF-7, BST-1 or Mo5) has ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities. CD157 supports the growth of a pre-B cell line, DW34. Anti-CD157 mAb IF-7 has synergistic effects on anti-CD3-induced growth of T progenitor cells, and facilitates the development of [alpha][beta] TCR+ cells in foetal thymic organ culture system.
Transcription initiation factor IIA, gamma subunit (TFIIA_gsu)
Type: Family

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .

This entry represents the gamma subunit of transcription factor TFIIA.
Transcription initiation factor IID, subunit 13 (TFIID_TAF13)
Type: Family

This family includes the Spt3 yeast transcription factors and the 18kDa subunit from human transcription initiation factor IID, known as TAF13 or TAFII18. Determination of the crystal structure reveals an atypical histone fold .

TBP-associated factor 13 (TAF13) is one of several TAFs that bind TBP and is involved in forming the transcription factor IID (TFIID) complex. TAF13 interacts with TAF11 and makes a histone-like heterodimer similar to H3/H4-like proteins. The dimer may be structurally and functionally similar to the spt3 protein within the SAGA histone acetyltransferase complex .

TFIID is one of seven General Transcription Factors (GTF) (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIID) that are involved in accurate initiation of transcription by RNA polymerase II in eukaryotes. TFIID plays an important role in the recognition of promoter DNA and assembly of the pre-initiation complex. TFIID complex is composed of the TBP and at least 13 TAFs. Each TAF, with the help of a specific activator, is required only for expression of subset of genes and is not universally involved for transcription as are GTFs. In yeast and human cells, TAFs have been found as components of other complexes besides TFIID. Several TAFs interact via histone-fold (HFD) motifs; the HFD is the interaction motif involved in heterodimerization of the core histones and their assembly into nucleosome octamers. The minimal HFD contains three α-helices linked by two loops and are found in core histones, TAFs and many other transcription factors. TFIID has a histone octamer-like substructure.
Transcription initiation factor IIF, beta subunit (TFIIF_beta)
Type: Family

Accurate transcription
in vivo
requires at least six general transcription initiation factors, in addition to RNA polymerase II. Transcription initiation factor IIF (TFIIF) is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30) . The beta subunit of TFIIF is required for recruitment of RNA polymerase II onto the promoter.
Cytochrome b-c1 complex subunit 7 (QCR7)
Type: Family

Cytochrome b-c1 complex subunit 7 (QCR7, also known as UQCRB) is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. QCR7 is involved in redox-linked proton pumping .
Nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase (Nict_dMeBzImd_PRibTrfase)
Type: Family

This entry represents bacterial- and archaeal-type nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase enzymes involved in dimethylbenzimidazole synthesis, as well as a group of proteins of unknown function. This function is essential to
de novo
cobalamin (vitamin B12) production in bacteria.

Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin . It is one of the enzymes of the anaerobic pathway of cobalamin biosynthesis, and one of the four proteins (CobU, CobT, CobC, and CobS) involved in the synthesis of the lower ligand and the assembly of the nucleotide loop .

Vitamin B
12
(cobalamin) is used as a cofactor in a number of enzyme-catalysed reactions in bacteria, archaea and eukaryotes . The biosynthetic pathway to adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolaevulinic acid; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin 6 or cobalt-precorrin 6; and (3) the transformation of this intermediate to form adenosylcobalamin . Cobalamin is synthesised by bacteria and archaea via two alternative routes that differ primarily in the steps of section 2 that lead to the contraction of the macrocycle and excision of the extruded carbon molecule (and its attached methyl group) . One pathway (exemplified by Pseudomonas denitrificans) incorporates molecular oxygen into the macrocycle as a prerequisite to ring contraction, and has consequently been termed the aerobic pathway. The alternative, anaerobic, route (exemplified by Salmonella typhimurium) takes advantage of a chelated cobalt ion, in the absence of oxygen, to set the stage for ring contraction .
Transposase Tn5, dimerisation (Transposase_Tn5)
Type: Domain

Transposons are mobile DNA sequences capable of replication and insertion into the chromosome. Typically transposons code for the transposase enzyme, which catalyses insertion, found between terminal inverted repeats . Tn5 has a unique method of self- regulation in which a truncated version of the transposase enzyme acts as an inhibitor .
DNA polymerase processivity factor (UL42) (Herpes_UL42)
Type: Family

The DNA polymerase processivity factor (UL42) of Human herpesvirus 1 (HHV-1) forms a heterodimer with UL30 to create the viral DNA polymerase complex. UL42 functions to increase the processivity of polymerisation and makes little contribution to the catalytic activity of the polymerase.
Bifunctional adenosylcobalamin biosynthesis protein CobU/CobP (CobU/CobP)
Type: Family

This family includes Bifunctional adenosylcobalamin biosynthesis protein CobU, Bifunctional adenosylcobalamin biosynthesis protein CobP and similar proteins mainly found in bacteria. This group of bifunctional cobalamin biosynthesis enzymes display cobinamide kinase and cobinamide phosphate guanyltransferase activity. The crystal structure of the enzyme reveals the molecule to be a trimer with a propeller-like shape .
Cytochrome c oxidase, subunit Va/VI (Cyt_c_oxidase_su5A/6)
Type: Family

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex are encoded within the mitochondrial genome, there are a variable number of small polypeptidic subunits encoded within the nuclear genome. This entry represents subunits Va and VI, which are the heme A-containing chains of cytochrome c oxidase. Subunit Va is one of three mammalian subunits that lacks a transmembrane region. Subunit Va is located on the matrix side of the membrane and binds thyroid hormone T2, releasing allosteric inhibition caused by the binding of ATP to subunit IV and allowing high turnover at elevated intramitochondrial ATP/ADP ratios .
Cytochrome c oxidase, subunit 8 (Cyt_c_oxidase_su8)
Type: Family

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In fungi (as in other eukaryotes) this enzyme complex is located in the mitochondrial inner membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptide subunits. This family includes fungal-type cytochrome-c oxidase, subunit VIIa, also known as cytochrome c oxidase subunit 8 .
Diol/glycerol dehydratase, large subunit (Diol/glycerol_deHydtase_lsu)
Type: Domain

This entry represents the large subunit of adenosylcobalamin-dependent diol dehydratases (

) and glycerol dehydratases (

). These enzymes are produced by some enterobacteria in response to growth substances. The enzyme have an TIM β/α barrel fold . Inactivated holoenzymes are reactivated by their own reactivating factors that mediate the ATP-dependent exchange of an enzyme-bound, damaged cofactor for free adenosylcobalamin through intermediary formation of apoenzyme. The reactivation takes place in two steps: (a) ADP-dependent cobalamin release and (b) ATP-dependent dissociation of the resulting apoenzyme-reactivating factor complexes .
Propanediol/glycerol dehydratase, small subunit (Ppandiol/glycerol_DeHydtase_su)
Type: Family

Diol dehydratase (

) and glycerol dehydratase (

) are two iso-functional enzymes that can each catalyse the conversion of 1,2-propanediol, 1,2-ethanediol and glycerol to the corresponding deoxy aldehydes (propionaldehyde, acetaldehyde and 3-hydroxypropionaldehyde, respectively). This reaction proceeds by a radical mechanism involving coenzyme B12 (adenosylcobalamin, AdoCbl) as an essential cofactor. Even though they catalyse the same reaction, these two enzymes (1) differ in their substrate preferences (diol dehydratase has a higher affinity for 1,2-propanediol and glycerol dehydratase for glycerol ); (2) they participate in different pathways (dihydroxyacetone [DHA] pathway for glycerol dehydratase and 1,2-propanediol degradation pathway for diol dehydratase); and (3) in those organisms where both enzymes are produced (such as Klebsiella and Citrobacter), the genes for them are independently regulated: glycerol dehydratase is induced when Klebsiella pneumoniae grows in glycerol-containing medium, whereas diol dehydratase is fully induced when it grows in propane-1,2-diol-containing medium, but only slightly in the glycerol medium .

Both diol dehydratase and glycerol dehydratase comprise three subunits: PduC/PduD/PduE or PddA/PddB/PddC for propanediol dehydratase, and GldA/Gld/B/GldC or DhaB/DhaC/DhaE for glycerol dehydratase. This entry represents the small subunit PduE/PddC/GldC/DhaE.
Diol/glycerol dehydratase/dehydratase reactivating factor (Dehydtase/Dehydtase_re)
Type: Family

This family contains the medium subunit of the trimeric diol dehydratases and glycerol dehydratases, and the small subunit of the diol/glycerol dehydratase reactivating factor . Diol dehydratases are produced by some enterobacteria in response to growth substances .

Both diol dehydratase and glycerol dehydratase comprise three subunits: PduC/PduD/PduE or PddA/PddB/PddC for propanediol dehydratase, and GldA/Gld/B/GldC or DhaB/DhaC/DhaE for glycerol dehydratase.
Methenyltetrahydromethanopterin cyclohydrolase (METHMP_CycHdrlase)
Type: Family

Methenyltetrahydromethanopterin cyclohydrolase (

) catalyses the interconversion of methenyltetrahydromethanopterin and N(5)formyltetrahydromethanopterin, and is found in both archaea and bacteria. In methanogenic archaea, such as Methanobacterium thermoautotrophicum (strain Marburg / DSM 2133), this enzyme is involved in the production of methane from carbon dioxide . In the sulphate-reducer Archaeoglobus fulgidus, this enzyme is involved in the tetrahydromethanopterin-dependent oxidation of lactate . In Gram-negative methylotrophic bacteria this enzyme is involved in the tetrahydromethanopterin-dependent oxidation of formaldehyde to formate . The protein functions as a homodimer or homotrimer, depending on the organism.
Signal recognition particle, SRP14 subunit (Signal_recog_particle_SRP14)
Type: Family

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the 14kDa SRP14 component. Both SRP9 and SRP14 have the same (β)-α-β(3)-α fold. The heterodimer has pseudo two-fold symmetry and is saddle-like, consisting of a curved six-stranded β-sheet that has four helices packed on the convex side and an exposed concave surface lined with positively charged residues. The SRP9/SRP14 heterodimer is essential for SRP RNA binding, mediating the pausing of synthesis of ribosome associated nascent polypeptides that have been engaged by the targeting domain of SRP .