SII-SWORD/CoKE huggingface dataset:
Haem oxygenase-like (Haem_Oase-like)
Type: Family

Haem oxygenase (

) (HO) is the microsomal enzyme that, in animals, carries out the oxidation of haem, it cleaves the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide . Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. It has been suggested that HO-2 could be implicated in the production of carbon monoxide in the brain where it is said to act as a neurotransmitter. In the genome of the chloroplast of red algae as well as in cyanobacteria, there is a haem oxygenase (gene pbsA) that is the key enzyme in the synthesis of the chromophoric part of the photosynthetic antennae . A haem oxygenase is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where it is involved in the acquisition of iron from the host haem . There is, in the central section of these enzymes, a well-conserved region centred on a histidine residue.
Ly-6 antigen/uPA receptor-like (LY6_UPA_recep-like)
Type: Domain

This entry represents a three-fold repeated domain that is found in a number of venomous neuro- and cytotoxins from snakes as well as in cell receptors such as urokinase-type plasminogen activator receptor (uPAR) that occurs singly in other GPI-linked cell-surface glycoproteins (Ly-6 family, CD59).

A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved domain of about 100 amino-acid residues . Among these proteins, U-PAR contains three tandem copies of the domain, while all the others are made up of a single domain.

As shown in the following schematic, this conserved domain contains 10 cysteine residues involved in five disulphide bonds -in U-PAR, the first copy of the domain lacks the fourth disulphide bond.

+------+ +------------------------+ +---+
| | | | | |
xCxxCxxxxxxCxxxxxCxxxxxCxxxxxxxxxxxxxxxxxxCxxxxCxxxxxxxxxxxxxxCCxxxCxxxxxxxx
| | | |
+---------------------+ +--------------+

'C': conserved cysteine involved in a disulphide bond.
Alpha-D-phosphohexomutase, alpha/beta/alpha I/II/III (A-D-PHexomutase_a/b/a-I/II/III)
Type: Homologous_superfamily

This superfamily represents domains I, II and III found in alpha-D-phosphohexomutase enzymes. All three domains share a 3-layer α/β/α topology.

The alpha-D-phosphohexomutase superfamily is composed of four related enzymes, each of which catalyses a phosphoryl transfer on their sugar substrates: phosphoglucomutase (PGM), phosphoglucomutase/phosphomannomutase (PGM/PMM), phosphoglucosamine mutase (PNGM), and phosphoacetylglucosamine mutase (PAGM) . PGM (

) converts D-glucose 1-phosphate into D-glucose 6-phosphate, and participates in both the breakdown and synthesis of glucose . PGM/PMM (

;

) are primarily bacterial enzymes that use either glucose or mannose as substrate, participating in the biosynthesis of a variety of carbohydrates such as lipopolysaccharides and alginate . Both PNGM (

) and PAGM (

) are involved in the biosynthesis of UDP-N-acetylglucosamine .
Pheromone Er-23, protozoan (Pheromone_Er23_protoz)
Type: Homologous_superfamily

Protozoan pheromones are cell-type specific protein signals. This entry represents the mating ciliate pheromone (or gamone) Er-23 from the protozoan Euplotes raikovi. Er-23 is a diffusible extracellular communication signal that distinguishes different intra-specific classes of cells commonly referred to as 'mating types'. Er-23 prepares these cells for conjugation by changing its cell surface properties. The mitogenic activity induced by the Er pheromone autocrine signalling can be inhibited by cAMP . The NMR structure of Er-23 reveals an all-α topology that is rich in disulphide bonds . In some cases, different pheromones can compete with each other in binding to their cell-surface receptors.
Pheromone Er-2/Er-23, protozoan (Pheromone_Er2/Er23_protoz)
Type: Homologous_superfamily

Protozoan pheromones are cell-type specific protein signals. This entry represents the mating ciliate pheromones (or gamones) Er-2 and Er-23 from the protozoan Euplotes raikovi. These pheromones are diffusible extracellular communication signals that distinguishes different intra-specific classes of cells commonly referred to as 'mating types'. Pheromones prepare these cells for conjugation by changing their cell surface properties. The mitogenic activity induced by the Er pheromone autocrine signalling can be inhibited by cAMP . The NMR structures of Er-2 and Er-23 reveal an all-alpha orthogonal bundle topology . In some cases, different pheromones can compete with each other in binding to their cell-surface receptors.
Pheromone Er-1, protozoan (Pheromone_Er1_protoz)
Type: Homologous_superfamily

Protozoan pheromones are cell-type specific protein signals. This entry represents the mating ciliate pheromone (or gamone) Er-1 from the protozoan Euplotes raikovi. Er-1 is a diffusible extracellular communication signal that distinguishes different intra-specific classes of cells commonly referred to as 'mating types'. Er-1 prepares these cells for conjugation by changing its cell surface properties. Er-1 exists as membrane-bound and secreted forms, where the membrane-bound form promotes inter-cellular communication and adhesion for mating pair formation and may act as binding site for the secreted form. The mitogenic activity induced by the Er pheromone autocrine signalling can be inhibited by cAMP . The NMR structure of Er-1 reveals an all-alpha orthogonal bundle topology . In some cases, different pheromones can compete with each other in binding to their cell-surface receptors.
DNA ligase, ATP-dependent, conserved site (DNA_ligase_ATP-dep_CS)
Type: Conserved_site

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (

), the other NAD (

), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination .

Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallelβ-sheets flanked by α-helices, whereas domain 2 consists of a five-stranded β-barrel and a single α-helix, which form the oligonucleotide-binding fold .
Proline-tRNA ligase, class II, C-terminal (Pro-tRNA_ligase_II_C)
Type: Domain

Proline tRNA ligase (also known as Prolyl tRNA synthetase) (

) exists in two forms, which are loosely related. The first form is present in the majority of eubacteria species. The second one, present in some eubacteria, is essentially present in archaea and eukaryota. Proline-tRNA ligase belongs to class IIa.

This domain is found at the C-terminal in archaeal and eukaryotic enzymes, as well as in certain bacterial ones.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Hypothetical protein TM1410-related (TM1410-rel)
Type: Family

Eighty-one archaeal-like genes, ranging in size from 4-20kb, are clustered in 15 regions of the Thermotoga maritima genome . Conservation of gene order between T. maritima and Archaea in many of these regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea .
TM1410 putative glycosidase (TM1410_Glycdase)
Type: Family

This is a family of uncharacterised proteins. Family members were initially considered to be putative cysteinyl-tRNA synthetases, , but this is no longer thought to be the case. The sequences have a signal peptide. Members of this family occur in Deinococcus radiodurans (bacterial) and Methanococcus jannaschii (archaeal). They are likely to be extracellular proteins.

The structure of a member of this family from Thermotoga maritima has been determined (

) and revealed TIM barrel-like topology with similarity to Transglycosidases.
NAD kinase/diacylglycerol kinase-like domain superfamily (NAD/diacylglycerol_kinase_sf)
Type: Homologous_superfamily

ATP-NAD kinases (

) catalyse the phosphorylation of NAD to NADP utilizing ATP and other nucleoside triphosphates as well as inorganic polyphosphate as a source of phosphorus. ATP-NAD kinase contains two domains, where domain 1 has an α/β topology that is related in structure to the N-terminal of phosphofructokinase, and domain 2 has an atypical β-sandwich topology made of four structural repeats of beta(3) units .
Alpha-D-phosphohexomutase, conserved site (A-D-PHexomutase_CS)
Type: Conserved_site

The alpha-D-phosphohexomutase superfamily is composed of four related enzymes, each of which catalyses a phosphoryl transfer on their sugar substrates: phosphoglucomutase (PGM), phosphoglucomutase/phosphomannomutase (PGM/PMM), phosphoglucosamine mutase (PNGM), and phosphoacetylglucosamine mutase (PAGM) . PGM (

) converts D-glucose 1-phosphate into D-glucose 6-phosphate, and participates in both the breakdown and synthesis of glucose . PGM/PMM (

;

) are primarily bacterial enzymes that use either glucose or mannose as substrate, participating in the biosynthesis of a variety of carbohydrates such as lipopolysaccharides and alginate . Both PNGM (

) and PAGM (

) are involved in the biosynthesis of UDP-N-acetylglucosamine .

This entry represents the conserved site at the N-terminal region of alpha-D-phosphohexomutase enzymes.
S-adenosylmethionine decarboxylase, core (S-AdoMet_deCO2ase_core)
Type: Homologous_superfamily

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.
Translin, N-terminal (Translin_N)
Type: Homologous_superfamily

Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-sranded DNA ends generated by staggered breaks occuring at recombination hot spots .

Translin folds into an α-α superhelix, consisting of two curved layers of α/α topology . This structure can be divided into two α-bundle subdomains. This entry represents the N-terminal α bundle subdomain.
Translin, C-terminal (Translin_C)
Type: Homologous_superfamily

Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-sranded DNA ends generated by staggered breaks occuring at recombination hot spots .

Translin folds into an α-α superhelix, consisting of two curved layers of α/α topology . This structure can be divided into two α-bundle subdomains. This entry represents the C-terminal α bundle subdomain.
Staphylococcal nuclease (SNase-like), OB-fold (Staphylococal_nuclease_OB-fold)
Type: Domain

Staphylococcus aureus nuclease (SNase) homologues, previously thought to be restricted to bacteria and archaea, are also in eukaryotes. Staphylococcal nuclease has a multi-domain organisation . The human cellular coactivator p100 contains four repeats, each of which is a SNase homologue. These repeats are unlikely to possess SNase-like activities as each lacks equivalent SNase catalytic residues, yet they may mediate p100's single-stranded DNA-binding function . A variety of proteins including many that are still uncharacterised belong to this group.

SNase domains have an OB-fold consisting of a closed or partly open β-barrel with Greek key topology .
SKP1 component, dimerisation (Skp1_comp_dimer)
Type: Domain

SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex . It was found to bind several F-box containing proteins (e.g., Cdc4, Skp2, cyclin F) and to be involved in the ubiquitin protein degradation pathway. A yeast homologue of SKP1 (P52286) was identified in the centromere bound kinetochore complex and is also involved in the ubiquitin pathway . In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 .

This entry represents a dimerisation domain found at the C-terminal of SKP1 proteins , as well as in subunit D of the centromere DNA-binding protein complex Cbf3 . This domain is multi-helical in structure, and consists of an interlocked herterodimer in F-box proteins.
SKP1 component, POZ domain (Skp1_comp_POZ)
Type: Domain

SKP1 (together with SKP2) was identified as an essential component of the cyclin A-CDK2 S phase kinase complex . It was found to bind several F-box containing proteins (e.g., Cdc4, Skp2, cyclin F) and to be involved in the ubiquitin protein degradation pathway. A yeast homologue of SKP1 (P52286) was identified in the centromere bound kinetochore complex and is also involved in the ubiquitin pathway . In Dictyostelium discoideum (Slime mold) FP21 was shown to be glycosylated in the cytosol and has homology to SKP1 .

This entry represents a POZ domain with a core structure consisting of β(2)/α(2)/β(2)/α(2) in two layers, α/β. This domain is found at the N-terminal of SKP1 proteins as well as in subunit D of the centromere DNA-binding protein complex Cbf3 .
RNA polymerase, phosphoprotein P, C-terminal XD, paramyxovirinae (RNA_pol_Pprot-P_XD_paramyxovir)
Type: Homologous_superfamily

Paramyxovirinae has a negative-sense ssRNA genome that is packaged by the viral nucleoprotein (N) within a helical nucleocapsid. The N-RNA (nucleoprotein-RNA) complex is used as a template for both transcription and replication. During viral genome replication, the synthesis of viral RNA and its encapsidation by N are concomitant. Viral transcription and replication are carried out by viral RNA-dependent RNA polymerase, which consists of two proteins: L polymerase and phosphoprotein P. The L polymerase carries the enzyme activity. Phosphoprotein P binds the viral nucleocapsid, and positions the L polymerase on the template for transcription and replication formed by nucleoprotein-RNA (N-RNA).
Haem oxygenase-like, multi-helical (Haem_Oase-like_multi-hlx)
Type: Homologous_superfamily

This superfamily represents a multi-helical structural domain consisting of two structural repeats (duplication) of a 3-helical motif. This domain can be found in both eukaryotic and prokaryotic haem oxygenases , in TENA/THI-4 proteins that lack the haem-binding site , and in coenzyme PQQ (pyrrolo-quinoline-quinone) biosynthesis protein C (PqqC) .

Haem oxygenase (

) (HO) is the microsomal enzyme that, in animals, carries out the oxidation of haem, cleaving the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. Haem oxygenase is also present in certain bacteria, where it is involved in the acquisition of iron from the host haem.

The THI-4 protein is involved in thiamine biosynthesis, while TENA is one of a number of proteins that enhance the expression of extracellular enzymes, such as alkaline protease, neutral protease and levansucrase.

Coenzyme PQQ (pyrrolo-quinoline-quinone) biosynthesis protein C (PqqC;

) is required for the synthesis of PQQ, where PQQ is a prosthetic group found in several bacterial enzymes, including methanol dehydrogenase of methylotrophs and the glucose dehydrogenase of a number of bacteria.
Protease inhibitor, beta-barrel domain (Protease_inh_B-barrel_dom)
Type: Homologous_superfamily

This entry represents a β-barrel domain found in the protease inhibitors staphostatin and metalloprotease inhibitor .
Chalcone isomerase (Chalcone_isomerase)
Type: Domain

Chalcone isomerase (CHI,

; also known as chalcone-flavanone isomerase) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida (Petunia) genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone isomerase. Chalcone isomerase has a core 2-layer α/β structure consisting of β(3)-α(2)-β-α(2)-β(3) .

Altered inheritance of mitochondria protein 18/46, mitochondrial (AIM18/16) are CHI-like proteins from Saccharomyces cerevisiae, which lacks other enzymes of the flavonoid pathway. They show a similar fold to CHI with an extra fungal-specific loop. Instead of the chalcone isomerase activity these proteins bind heme, and structural prediction suggest this domain might be related to bacterial cytochrome P460 .

This entry represents the chalcone isomerases domain found in proteins from plants, fungi and bacteria.
Chalcone isomerase, 3-layer sandwich (Chalcone_isomerase_3-sand)
Type: Homologous_superfamily

Chalcone isomerase (

; also known as chalcone-flavanone isomerase or fatty-acid-binding protein) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida (Petunia) genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone isomerase. This entry represents a 3-layer β/β/α sandwich subdomain found in chalcone isomerases .
Chalcone isomerase, orthogonal bundle domain superfamily (Chalcone_isomerase_bundle_sf)
Type: Homologous_superfamily

Chalcone isomerase (

; also known as chalcone-flavanone isomerase or fatty-acid-binding protein) is a plant enzyme responsible for the isomerisation of chalcone to naringenin, a key step in the biosynthesis of flavonoids. The Petunia hybrida (Petunia) genome contains two genes coding for very similar enzymes, ChiA and ChiB, but only the first seems to encode a functional chalcone isomerase. This superfamily represents an α-helical orthogonal bundle subdomain found in chalcone isomerases .
Phospholipase A2-like, central domain (PLA2-like_dom)
Type: Domain

Proteins containing this domain include eukaryotic phospholipase A2 enzymes (PLA2;

), small lipolytic enzymes that release fatty acids from the second carbon group of glycerol, usually in a metal-dependent reaction, to generate lysophospholipid (LysoPL) and a free fatty acid (FA) . The resulting products are either dietary or used in synthetic pathways for leukotrienes and prostaglandins. Often, arachidonic acid is released as a free fatty acid and acts as a second messenger in signalling networks . These enzymes enable the hydrolysis of fatty acids and lysophospholipids by hydrolysing the 2-ester bond of 1,2-diacyl-3-sn-phosphoglycerides.

Phospholipase A2 (

) (PLA2 or PLA2G1B) is a small lipolytic enzyme that releases fatty acids from the second carbon group of glycerol. It is involved in a number of physiologically important cellular processes, such as the liberation of arachidonic acid from membrane phospholipids . It plays a pivotal role in the biosynthesis of prostaglandin and other mediators of inflammation. PLA2 has four to seven disulphide bonds and binds a calcium ion that is essential for activity. Within the active enzyme, the alpha amino group is involved in a conserved hydrogen-bonding network linking the N-terminal region to the active site. The side chains of two conserved residues, His and Asp, participate in the catalytic network.

Many PLA2's are widely distributed in snakes, lizards, bees, and mammals. In mammals, there are at least four forms: pancreatic, membrane-associated, as well as two less well characterised forms. The venom of most snakes contains multiple forms of PLA2 . Some of them are presynaptic neurotoxins, which inhibit neuromuscular transmission by blocking acetylcholine release from the nerve termini.

Some of the proteins in this family are allergens . Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Api m 1.