SII-SWORD/CoKE huggingface dataset:
Asparaginase/glutaminase, active site 1 (Asparaginase/glutaminase_AS1)
Type: Active_site

Asparaginase, which is found in various plant, animal and bacterial cells, catalyses the deamination of asparagine to yield aspartic acid and an ammonium ion, resulting in a depletion of free circulatory asparagine in plasma . The enzyme is effective in the treatment of human malignant lymphomas, which have a diminished capacity to produce asparagine synthetase: in order to survive, such cells absorb asparagine from blood plasma - if Asn levels have been depleted by injection of asparaginase, the lymphoma cells die. Glutaminase, a similar enzyme, catalyses the deaminination of glutamine to glutamic acid and an ammonium ion . Both enzymes are homotetramers : two threonine residues in the N-terminal half of the proteins are involved in the catalytic activity.

Two conserved threonine residues have been shown to play a catalytic role . One of them is located in the N-terminal extremity while the second is located at the end of the first third of the sequence. This entry represents the first conserved site.
Glyceraldehyde 3-phosphate dehydrogenase, NAD(P) binding domain (GlycerAld_3-P_DH_NAD(P)-bd)
Type: Domain

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain . The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme .

GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis . The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.

GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins .

This entry represents the N-terminal domain which is a Rossmann NAD(P) binding fold.
Glyceraldehyde 3-phosphate dehydrogenase, catalytic domain (GlycerAld_3-P_DH_cat)
Type: Domain

This entry represents the C-terminal domain which is a mixed α/antiparallel-β-fold.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain . The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme .

GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis . The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.

GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins .
Glyceraldehyde 3-phosphate dehydrogenase, active site (GlycerAld_3-P_DH_AS)
Type: Active_site

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain . The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme .

GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis . The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.

GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins .

A cysteine in the middle of the molecule is involved in forming a covalent phosphoglycerol thioester intermediate. The sequence around this cysteine is totally conserved in eubacterial and eukaryotic GAPDHs and is also present, albeit in a variant form, in the otherwise highly divergent archaebacterial GAPDH . The pattern in this entry represents the active site.
Glyceraldehyde/Erythrose phosphate dehydrogenase family (GlycerAld/Erythrose_P_DH)
Type: Family

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain . The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme .

GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis . The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.

GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins .

This entry contains a small clade of dehydrogenases in gammaproteobacteria which utilise NAD+ to oxidize erythrose-4-phosphate (E4P) to 4-phospho-erythronate, a precursor for the de novo synthesis of pyridoxine via 4-hydroxythreonine and D-1-deoxyxylulose . This enzyme activity appears to have evolved from glyceraldehyde-3-phosphate dehydrogenase, whose substrate differs only in the lack of one carbon relative to E4P. It is possible that some of the GAPDH enzymes may prove to be bifunctional in certain species.
Lipoxygenase, iron binding site (LipOase_Fe_BS)
Type: Binding_site

Lipoxygenases ([ec:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes . Sequence data is available for the following lipoxygenases:

Plant lipoxygenases (

). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme .

Mammalian arachidonate 5-lipoxygenase (

).

Mammalian arachidonate 12-lipoxygenase (

).

Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;

).

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.

This entry represents a motif that contains the iron-binding sites.
Lipoxygenase, conserved site (LipOase_CS)
Type: Conserved_site

Lipoxygenases ([ec:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes . Sequence data is available for the following lipoxygenases:

Plant lipoxygenases (

). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme .

Mammalian arachidonate 5-lipoxygenase (

).

Mammalian arachidonate 12-lipoxygenase (

).

Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;

).

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.

This entry represents a motif that contains two of the conserved histidines.
Catalase superfamily (Catalase_sf)
Type: Homologous_superfamily

This entry represents a fold found in the mono-functional, haem-containing catalases and also in haem peroxidases such as allene oxide synthase . In catalases, this entry covers the core forming domain and, if present, the immune-responsive C-terminal domain.
Fibrinogen, conserved site (Fibrinogen_CS)
Type: Conserved_site

Fibrinogen plays key roles in both blood clotting and platelet aggregation. During blood clot formation, the conversion of soluble fibrinogen to insoluble fibrin is triggered by thrombin, resulting in the polymerisation of fibrin, which forms a soft clot; this is then converted to a hard clot by factor XIIIA, which cross-links fibrin molecules. Platelet aggregation involves the binding of the platelet protein receptor integrin α(IIb)-β(3) to the C-terminal D domain of fibrinogen . In addition to platelet aggregation, platelet-fibrinogen interaction mediates both adhesion and fibrin clot retraction.

This entry represents a conserved site in the C-terminal globular D domain of the alpha, beta and gamma chains. These domains are related to domains in other proteins: in the Parastichopus parvimensis (Sea cucumber) fibrogen-like FreP-A and FreP-B proteins; in the C terminus of the Drosophila scabrous protein that is involved in the regulation of neurogenesis, possibly through the inhibition of R8 cell differentiation; and in ficolin proteins, which display lectin activity towards N-acetylglucosamine through their fibrogen-like domains .
DBINO domain (DBINO)
Type: Domain

Proteins belonging to the SNF2 family of DNA dependent ATPases are important members of the chromatin remodelling complexes that are implicated in epigenetic control of gene expression. Members of the SNF2 family of proteins
have been identified in organisms ranging from Escherichia coli to Homo sapiens (Human). All of them contain the conserved SNF2 domain, which is defined by the existence of seven motifs (I, Ia, and II-VI) with sequences similarity to those motifs found in DNA and RNA helicases (see

). SNF2-like family members can be further subdivided into several subfamilies according to the presence of protein motifs outside of the ATPase region. The DBINO (DNA binding domain of INO80) domain is characteristic of the INO80 subfamily and is a DNA-binding domain . The DBINO domain is a 126 amino acid long peptide located near the N terminus, approximately 100 residues upstream of the SNF2 helicase domain. The presence of this domain in all the INO80 subfamily proteins from yeast to humans suggests its conserved function in evolution .
Stromalin conservative domain (SCD)
Type: Domain

The stromal antigens or stromalins are a group of highly conserved nuclear proteins, originally identified from a murine bone marrows stromal cell line. Stromalins are represented in several organisms from yeast to humans and are characterised by the stromalin conservative domain (SCD), an 86 amino acid motif found in all proteins of the family described to date .

Some proteins known to contain a stromalin conservative domain are listed below:

Vertebrate cohesin subunits SA-1, -2 and -3 (Stag1, 2 and 3), components of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.

Human STAG3-like protein.

Yeast cohesin subunit SCC3, a component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.

Fission yeast meiotic recombination protein Rec11.
Extracellular matrix-binding protein ebh, GA module (Extracell_matrix-bd_GA)
Type: Domain

This entry represents the GA module from the extracellular matrix-binding protein ebhB.

Protein G-related albumin-binding (GA) modules occur on the surface of numerous Gram-positive bacterial pathogens. Protein G of group C and G Streptococci interacts with the constant region of IgG and with human serum albumin. The GA module is composed of a left-handed three-helix bundle and is found in a range of bacterial cell surface proteins . GA modules may promote bacterial growth and virulence in mammalian hosts by scavenging albumin-bound nutrients and camouflaging the bacteria. Variations in sequence give rise to differences in structure and function between GA modules in different proteins, which could alter pathogenesis and host specificity due to their varied affinities for different species of albumin . Proteins containing a GA module include PAB from Peptostreptococcus magnus .
Polyketide synthase, beta-ketoacyl synthase domain (PKS_Beta-ketoAc_synthase_dom)
Type: Domain

This entry represents the beta-ketoacyl synthase region from a number of polyketide synthases including erythronolide synthase and the lovastatin nonaketide chain synthase.

Beta-ketoacyl-ACP synthase

(KAS) is the enzyme that catalyses the condensation of malonyl-ACP with the growing fatty acid chain. It is found as a component of a number of enzymatic systems, including fatty acid synthetase (FAS), which catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH; the multi-functional 6-methysalicylic acid synthase (MSAS) from Penicillium patulum , which is involved in the biosynthesis of a polyketide antibiotic; polyketide antibiotic synthase enzyme systems; Emericella nidulans multifunctional protein Wa, which is involved in the biosynthesis of conidial green pigment; Rhizobium nodulation protein nodE, which probably acts as a beta-ketoacyl synthase in the synthesis of the nodulation Nod factor fatty acyl chain; and yeast mitochondrial protein CEM1. The condensation reaction is a two step process, first the acyl component of an activated acyl primer is transferred to a cysteine residue of the enzyme and is then condensed with an activated malonyl donor with the concomitant release of carbon dioxide.
Enoylreductase domain (ER)
Type: Domain

This entry represents the enoylreductase domain (ER), which can be found in several types of enzymes, including polyketides synthase enzymes (PKSs), In PKSs, the ER domain catalyses the reduction of enzyme-bound 2-enoyl intermediates during polyketide biosynthesis . It can also be found in mammalian fatty acid synthases (FAS)

where they perform a similar function to PKS ER domains in fatty acid biosynthesis . The ER domain can also be present in mitochondrial fatty acid synthesis enzymes such as enoyl-[acyl-carrier-protein] reductase (MECR). Finally it can also be found in some dehydrogenases, particulary those in the medium-chain dehydrogenase/reductase (MDR) superfamily and dehydrogenase/reductase (SDR) superfamily .
Circadian clock protein KaiA, N-terminal (Circadian_clock_KaiA_N)
Type: Domain

This entry represents the N-terminal domain of KaiA.

Cyanobacteria are the most primitive organisms known to exhibit circadian rhythms. KaiA, kaiB and kaiC constitute the circadian clock
machinery in cyanobacteria, and kaiA activates kaiBC expression whereas kaiC represses it . Apparent homologues of kaiB and kaiC are found among non cyanobacteria eubacteria and the archaea. However kaiA appears confined within the cyanobacteria, which are the only prokaryotes with demonstrated circadian rhythms .

There are at least two types of kaiA proteins: long and short . The long versions consist of ~300 aminoacyl residues. There is limited sequence conservation in the N-terminal 200 residues of these proteins but a high degree of conservation in the C-terminal 100 residues. They thus appear to contain two independently folded domains, the amino and carboxyl regions, connected by a canonical linker. The short versions are essentially independent C-terminal domains.

The kaiA N-terminal domain consists of a central five-stranded (β1 to β5) parallel β-sheet flanked by two groups of α-helices (α1,
α4 and α2, α3) packed on either side of the β-sheet and an additional α-helix (α5) lying near the amino terminus of the central
β-strand . The structure of the N-terminal domain of kaiA is that of a pseudo-receiver domain, similar to those found in bacterial response regulators. Although the fold is that of a canonical receiver domain, the primary sequence is dissimilar, and it lacks the conserved aspartate residue necessary for phosphorylation. KaiA activation most likely involves direct protein-protein interactions of the N-terminal domain that result in functional modulation of the C-terminal effector domain.
The C-terminal kaiA domain is responsible for dimer formation, binding to kaiC, enhancing kaiC phosphorylation and generating the circadian oscillations . It adopts a novel all α-helical homodimeric structure . The kaiA C-terminal domain contains two parallel helix-hairpin-
helix motifs that form a four helix bundle, which represents a new protein folding motif.
AP endonuclease 1, binding site (AP_endonuclease_F1_BS)
Type: Binding_site

DNA damaging agents such as the anti-tumour drugs bleomycin and neocarzinostatin or those that generate oxygen radicals produce a variety of lesions in DNA. Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or strand breaks with atypical 3' termini. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3' terminus of DNA strand breaks.

AP endonucleases can be classified into two families based on sequence similarity. This family contains members of AP endonuclease family 1. Except for Rrp1 and arp, these enzymes are proteins of about 300 amino-acid residues. Rrp1 and arp both contain additional and unrelated sequences in their N-terminal section (about 400 residues for Rrp1 and 270 for arp).
AP endonuclease 1, conserved site (AP_endonuclease_F1_CS)
Type: Conserved_site

DNA damaging agents such as the anti-tumour drugs bleomycin and neocarzinostatin or those that generate oxygen radicals produce a variety of lesions in DNA. Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or strand breaks with atypical 3' termini. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3' terminus of DNA strand breaks.

AP endonucleases can be classified into two families based on sequence similarity. This family contains members of AP endonuclease family 1. Except for Rrp1 and arp, these enzymes are proteins of about 300 amino-acid residues. Rrp1 and arp both contain additional and unrelated sequences in their N-terminal section (about 400 residues for Rrp1 and 270 for arp). The proteins contain glutamate which has been shown in the Escherichia coli enzyme to bind a divalent metal ion such as magnesium or manganese.