SII-SWORD/CoKE huggingface dataset:
Threonine-tRNA ligase, class IIa (Thr-tRNA-ligase_IIa)
Type: Family

Threonine-tRNA ligase (also known as Threonyl-tRNA synthetase) (

) exists as a monomer and belongs to class IIa. The enzyme from Escherichia coli represses the translation of its own mRNA. The crystal structure of the complex between tRNA(Thr) and ThrRS show structural features that reveal novel strategies for providing specificity in tRNA selection. These include an amino-terminal domain containing a novel protein fold that makes minor groove contacts with the tRNA acceptor stem. The enzyme induces a large deformation of the anticodon loop, resulting in an interaction between two adjacent anticodon bases, which accounts for their prominent role in tRNA identity and translational regulation. A zinc ion found in the active site is implicated in amino acid recognition/discrimination . The zinc ion may act to ensure that only amino acids that possess a hydroxyl group attached to the β-position are activated .

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 .
Cytochrome c, class II (Cyt_c_II)
Type: Family

Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. CytC possess a wide range of properties and function in a large number of different redox processes. Ambler recognised four classes of cytC.
Cytochrome f (Cyt_f)
Type: Family

The cytochrome b6f integral membrane protein complex transfers electrons between the two reaction centre complexes of oxygenic photosynthetic membranes, and participates in formation of the transmembrane electrochemical proton gradient by also transferring protons from the stromal to the internal lumen compartment. The cytochrome b6f complex contains four polypeptides: cytochrome f (285 aa); cytochrome b6 (215 aa); Rieske iron-sulphur protein (179 aa); and subunit IV (160 aa) . In its structure and functions, the cytochrome b6f complex bears extensive analogy to the cytochrome bc1 complex of mitochondria and photosynthetic purple bacteria; cytochrome f (cyt f) plays a role analogous to that of cytochrome c1, in spite of their different structures .
Cytochrome c1 (Cyt_c1)
Type: Family

Cytochrome bc1 complex (ubiquinol:ferricytochrome c oxidoreductase) is found in mitochondria, photosynthetic bacteria and other prokaryotes. It is minimally composed of three subunits: cytochrome b, carrying a low- and a high-potential haem group; cytochrome c1 (cyt c1); and a high-potential Rieske iron-sulphur protein. The general function of the complex is electron transfer between two mobile redox carriers, ubiquinol and cytochrome c; the electron transfer is coupled with proton translocation across the membrane, thus generating proton-motive force in the form of an electrochemical potential that can drive ATP synthesis. In its structure and functions, the cytochrome bc1 complex bears extensive analogy to the cytochrome b6f complex of chloroplasts and cyanobacteria; cyt c1 plays an analogous role to cytochrome f, in spite of their different structures .

This entry also includes Nitrosomonas europaea petC, which is a subunit of the ammonia monooxygenase complex that catalyzes the oxidation of ammonia to hydroxylamine, the first reaction in the process of ammonia oxidation to nitrite .
Cytochrome c, class IA/ IB (Cyt_c_1A/1B)
Type: Family

Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more generally, two thioether bonds involving sulfhydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. CytC possess a wide range of properties and function in a large number of different redox processes.

Ambler recognised four classes of cytC. Class I includes the low-spin soluble cytC of mitochondria and bacteria, with the haem-attachment site towards the N terminus, and the sixth ligand provided by a methionine residue about 40 residues further on towards the C terminus . On the basis of sequence similarity, class I cytC were further subdivided into five classes, IA to IE. Class IB includes the eukaryotic mitochondrial cyt C and prokaryotic 'short' cyt C2 exemplified by Rhodopila globiformis cyt C2; Class IA includes 'long' cyt C2, such as Rhodospirillum rubrum cyt C2 and Aquaspirillum itersonii cyt C-550, which have several extra loops by comparison with Class IB cyt C.

Class I cytC has a characterised fold which comprises 5 α-helices arranged in a unique tertiary structure and a conserved N-terminal sequence -Cys-Xxx-Xxx-Cys-His- where the cysteines mediate the covalent cross-linking of the heme to the protein and the His .The 3D structures of a considerable number of class IA and IB cytC have been determined. The proteins consist of 3-6 α-helices; the three most conserved 'core' helices form a 'basket' around the haem group, with one haem edge exposed to the solvent. Most class I cytC have conserved aromatic residues clustered around the haem and axial ligands.
Lipoprotein lipase (Lipo_Lipase)
Type: Family

Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism that hydrolyses triglycerides, providing free fatty acids for cells and affecting the maturation of circulating lipoproteins . The enzyme is thought to play a role in the development of obesity and atherosclerosis . Human LPL contains 448 amino acids; sequence comparison indicates that human LPL, hepatic lipase, and pancreatic lipase are members of a gene family . Defects in LPL are a cause of familial chylomicronemia syndrome (or type I hyperlipoproteinemia) and also of a form of deficiency characterised by hypertriglyceridemia. Familial chylomicronemia is a recessive disorder usually manifesting in childhood. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. LPL and pancreatic lipase share ~30% sequence identity, suggesting a similar tertiary fold . Molecular models of LPL have been constructed, based on X-ray crystal structures of pancreatic lipase . These models allowed the authors to propose hypotheses on the structural determinants of LPL that are responsible for heparin binding, dimer formation, and phospholipase activity.
Pancreatic lipase (Lipase_panc)
Type: Family

Triglyceride lipases (

) are lipolytic enzymes that hydrolyse ester linkages of triglycerides . Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher vertebrates: pancreatic, hepatic and gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase (

), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL) . Pancreatic lipase (triacylglycerol acylhydrolase,

) plays a key role in dietary fat absorption by hydrolysing dietary long chain triacyl-glycerol to free fatty acids and monoacylglycerols in the intestinal lumen . The activity of lipase is stimulated by colipase in the presence of bile acids.

The 3D structure of human pancreatic lipase has been determined by X-ray crystallography . The enzyme is a single-chain glycoprotein of 449 amino acids. Structural results suggest that Ser 152 is the nucleophilic residue essential for catalysis . The residue is located in the N-terminal domain at the C-terminal edge of a doubly-wound parallel β-sheet, and forms part of an Asp-His-Ser triad that is chemically analogous to, but structurally different from, that of the serine proteases . The putative hydrolytic site is covered by a surface loop, and is thus inaccessible to solvent. It is thought that interfacial activation may involve a reorientation of this flap, not only in pancreatic lipases but also in the related hepatic and lipoprotein lipases .
Nitrogen regulatory protein P-II, urydylation site (N-reg_PII_urydylation_site)
Type: PTM

The P-II protein (gene glnB) is a bacterial protein important for the control of glutamine synthetase . In nitrogen-limiting conditions, when the ratio of glutamine to 2-ketoglutarate decreases, P-II is uridylylated on a tyrosine residue to form P-II-UMP. P-II-UMP allows the deadenylation of glutamine synthetase (GS), thus activating the enzyme. Conversely, in nitrogen excess, P-II-UMP is deuridylated and then promotes the adenylation of GS. P-II also indirectly controls the transcription of the GS gene (glnA) by preventing NR-II (ntrB) to phosphorylate NR-I (ntrC) which is the transcriptional activator of glnA. Once P-II is uridylylated, these events are reversed.

P-II is a protein of about 110 amino acid residues extremely well conserved. The tyrosine, which is uridylated, is located in the central part of the protein. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather than being uridylated. In the red alga, Porphyra purpurea, there is a glnB homologue encoded in the chloroplast genome. Other proteins highly similar to glnB include Bacillus subtilis protein nrgB ; and Escherichia coli hypothetical protein ybaI .

This entry represents a conserved stretch (in eubacteria) of six residues which contains the uridylated tyrosine.
Hepatic lipase (Lipase_hep)
Type: Family

Triglyceride lipases (

) are lipolytic enzymes that hydrolyse ester linkages of triglycerides . Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher vertebrates: pancreatic, hepatic and gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase (

), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL) . Familial human hepatic lipase deficiency is a rare recessive disorder that results from mutation in position 405 of the mature protein. The disease is characterised by premature atherosclerosis and abnormal circulating lipoproteins . The structure of the human hepatic triglyceride lipase gene has been determined . The hepatic lipase gene spans ~60 kb, and contains 8 introns and 9 exons: exon 1 encodes the signal peptide; exon 4, a region that binds to the lipoprotein substrate; exon 5, an evolutionarily highly-conserved region of potential catalytic function; and exons 6 and 9 encode sequences rich in basic amino acids, thought to be important in anchoring the enzyme to the endothelial surface by interacting with acidic domains of surface glycosaminoglycans . The human lipoprotein lipase gene has an identical exon-intron organisation, with analogous structural domains, supporting the common evolutionary origin of these two lipolytic enzymes .
Vespid venom allergen phospholipase A1 (Allerg_PlipaseA1)
Type: Family

The two principal allergenic proteins in vespid venoms are antigen 5s and phospholipases. The complete amino acid sequences of the venom phospholipase A1 from the yellow jacket, Vespula maculifrons, and the more acidic isoenzyme from the white faced hornet, Dolichovespula maculata, have been determined . The proteins, which contain approximately 300 amino acid residues, show no sequence similarity to other known phospholipases, but do have some similarity to mammalian lipases (~40% identity over 123 residues). Experimental evidence suggests that these phospholipases have weak lipase activity .

This type of phospholipase allergens can also be found in other arthropods .
Hemoglobin, beta-type (Hemoglobin_b)
Type: Family

In vertebrates, hemoglobins (Hb) function to transport oxygen in blood plasma. Hb binds oxygen in the reduced [Fe(II)] state. Hb is composed of four globins in a tetrahedral arrangement, typically two alpha and two beta globins, where each monomer binds a heme group. The alpha and beta subunits are highly similar in sequence, but differ structurally in that the beta subunit contains an α-helix (the D helix) that is missing in the alpha subunit . There is at least one heme-site ligand on each of the alpha and beta subunits. The imidazole ring of the 'proximal' His residue provides the fifth heme iron ligand; the other axial heme iron position remains essentially free for oxygen coordination. The binding of oxygen and carbon dioxide is associated with a variation of the heme iron coordination. Oxygen binding results in a transition from high-spin to low-spin iron, with accompanying changes in the Fe-N bond lengths and coordination geometry. In Hb, these subtle changes lead to the well-known cooperative effect of oxygen binding, which involves a relaxed (R) state when oxygen is bound and a tense (T) state upon oxygen release . The alpha or beta subunits are substituted in embryo and foetal Hb with subunits that have higher oxygen affinity (gamma, delta, epsilon, pi or zeta subunits). There are at least three types of human embryonic Hb (zeta2epsilon2, alpha2epsilon2, zeta2gamma2) and two foetal Hb (alpha2gamma2, alpha2delta2) . It has been hypothesised that the embryonic alpha-hemoglobin family diverged considerably earlier than the beta-hemoglobin line, as reflected in the greater diversity found amongst alpha sequences . Alpha-like globins derived from a common ancestor and have a more stable history than beta-globins .

This entry represents the Hemoglobin beta-type subunits.
Hemoglobin, alpha-type (Hemoglobin_a-typ)
Type: Family

In vertebrates, hemoglobins (Hb) function to transport oxygen in blood plasma. Hb binds oxygen in the reduced [Fe(II)] state. Hb is composed of four globins in a tetrahedral arrangement, typically two alpha and two beta globins, where each monomer binds a heme group. The alpha and beta subunits are highly similar in sequence, but differ structurally in that the beta subunit contains an α-helix (the D helix) that is missing in the alpha subunit . There is at least one heme-site ligand on each of the alpha and beta subunits. The imidazole ring of the 'proximal' His residue provides the fifth heme iron ligand; the other axial heme iron position remains essentially free for oxygen coordination. The binding of oxygen and carbon dioxide is associated with a variation of the heme iron coordination. Oxygen binding results in a transition from high-spin to low-spin iron, with accompanying changes in the Fe-N bond lengths and coordination geometry. In Hb, these subtle changes lead to the well-known cooperative effect of oxygen binding, which involves a relaxed (R) state when oxygen is bound and a tense (T) state upon oxygen release . The alpha or beta subunits are substituted in embryo and foetal Hb with subunits that have higher oxygen affinity (gamma, delta, epsilon, pi or zeta subunits). There are at least three types of human embryonic Hb (zeta2epsilon2, alpha2epsilon2, zeta2gamma2) and two foetal Hb (alpha2gamma2, alpha2delta2) . It has been hypothesised that the embryonic alpha-hemoglobin family diverged considerably earlier than the beta-hemoglobin line, as reflected in the greater diversity found amongst alpha sequences . Alpha-like globins derived from a common ancestor and have a more stable history than beta-globins .

This entry represents the adult and embryonic alpha-like hemoglobin subunits.
Hemoglobin, pi (Hemoglobin_pi)
Type: Family

In vertebrates, hemoglobins (Hb) function to transport oxygen in blood plasma. Hb binds oxygen in the reduced [Fe(II)] state. Hb is composed of four globins in a tetrahedral arrangement, typically two alpha and two beta globins, where each monomer binds a heme group. The alpha and beta subunits are highly similar in sequence, but differ structurally in that the beta subunit contains an α-helix (the D helix) that is missing in the alpha subunit . There is at least one heme-site ligand on each of the alpha and beta subunits. The imidazole ring of the 'proximal' His residue provides the fifth heme iron ligand; the other axial heme iron position remains essentially free for oxygen coordination. The binding of oxygen and carbon dioxide is associated with a variation of the heme iron coordination. Oxygen binding results in a transition from high-spin to low-spin iron, with accompanying changes in the Fe-N bond lengths and coordination geometry. In Hb, these subtle changes lead to the well-known cooperative effect of oxygen binding, which involves a relaxed (R) state when oxygen is bound and a tense (T) state upon oxygen release . The alpha or beta subunits are substituted in embryo and foetal Hb with subunits that have higher oxygen affinity (gamma, delta, epsilon, pi or zeta subunits). There are at least three types of human embryonic Hb (zeta2epsilon2, alpha2epsilon2, zeta2gamma2) and two foetal Hb (alpha2gamma2, alpha2delta2) . It has been hypothesised that the embryonic alpha-hemoglobin family diverged considerably earlier than the beta-hemoglobin line, as reflected in the greater diversity found amongst alpha sequences . Alpha-like globins derived from a common ancestor and have a more stable history than beta-globins .

This entry represents the pi-haemoglobin subunit, which is the counterpart of the alpha chain in the major early embryonic hemoglobin P. Pi is expressed during development only in the primitive erythrocyte lineage and not in the definitive lineage in chicken .
Hemoglobin, zeta (Hemoglobin_zeta)
Type: Family

In vertebrates, hemoglobins (Hb) function to transport oxygen in blood plasma. Hb binds oxygen in the reduced [Fe(II)] state. Hb is composed of four globins in a tetrahedral arrangement, typically two alpha and two beta globins, where each monomer binds a heme group. The alpha and beta subunits are highly similar in sequence, but differ structurally in that the beta subunit contains an α-helix (the D helix) that is missing in the alpha subunit . There is at least one heme-site ligand on each of the alpha and beta subunits. The imidazole ring of the 'proximal' His residue provides the fifth heme iron ligand; the other axial heme iron position remains essentially free for oxygen coordination. The binding of oxygen and carbon dioxide is associated with a variation of the heme iron coordination. Oxygen binding results in a transition from high-spin to low-spin iron, with accompanying changes in the Fe-N bond lengths and coordination geometry. In Hb, these subtle changes lead to the well-known cooperative effect of oxygen binding, which involves a relaxed (R) state when oxygen is bound and a tense (T) state upon oxygen release . The alpha or beta subunits are substituted in embryo and foetal Hb with subunits that have higher oxygen affinity (gamma, delta, epsilon, pi or zeta subunits). There are at least three types of human embryonic Hb (zeta2epsilon2, alpha2epsilon2, zeta2gamma2) and two foetal Hb (alpha2gamma2, alpha2delta2) . It has been hypothesised that the embryonic alpha-hemoglobin family diverged considerably earlier than the beta-hemoglobin line, as reflected in the greater diversity found amongst alpha sequences . Alpha-like globins derived from a common ancestor and have a more stable history than beta-globins .

This entry represents the zeta-hemoglobin subunit, which is expressed exclusively in the primitive erythroblasts of the embryonic yolk sac and is selectively silenced during the transition from primitive to definitive erythropoiesis .
Paraneoplastic encephalomyelitis antigen (Hud_Sxl_RNA)
Type: Family

Many eukaryotic proteins that are either known or thought to bind single-stranded RNA contain one or more copies of a putative RNA-binding domain of about 90 amino acids . This region has been found in, for example, heterogeneous nuclear ribonucleoproteins, small nuclear ribonucleoproteins, pre-RNA and mRNA associated proteins, Drosophila sex determination and elav proteins, human paraneoplastic encephalomyelitis antigen HuD, and many others. The structure of an RNA-binding domain of Drosophila Sex-lethal (Sxl) protein has been determined using multi-dimensional hetero-nuclear NMR . Sxl contains two RNP consensus-type RNA-binding domains (RBDs) - the determined structure represents the second of these (RBD-2) . The calculated intermediate-resolution family of structures exhibits the β-α-β/β-α-β tertiary fold found in other RBD-containing proteins .
Lupus La protein (Lupus_La)
Type: Family

The La protein is a 47kDa polypeptide that often acts as an autoantigen in systemic lupus erythematosus and Sjogren's syndrome patients . It occurs in both the nucleus and the cytoplasm, where it takes on different roles . In the nucleus, La facilitates the production of tRNAs, acting as a RNA polymerase III (RNAP III) transcription factor by binding to the U-rich 3'UTR of nascent transcripts, assisting in their folding and maturation . In the cytoplasm, La facilitates the translation of specific mRNAs, acting as a translation factor. As a RNA binding protein (RBP), La associates with subsets of mRNAs that contain a 5'-terminal oligopyrimidine (5'TOP) motif known to control protein synthesis. The binding of La to specific classes of RNA molecules regulates their downstream processing, protects them from endonuclease digestion, and organises their export from the nucleus .
Lipocalin (Lipocalin)
Type: Family

The lipocalins are a diverse, interesting, yet poorly understood family of proteins composed, in the main, of extracellular ligand-binding proteins displaying high specificity for small hydrophobic molecules . Functions of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis of prostaglandins. For example, retinol-binding protein 4 transfers retinol from the stores in the liver to peripheral tissues .

The crystal structures of several lipocalins have been solved and show a novel 8-stranded anti-parallel β-barrel fold well conserved within the family. Sequence similarity within the family is at a much lower level and would seem to be restricted to conserved disulphides and 3 motifs, which form a juxtaposed cluster that may act as a common cell surface receptor site . By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes . The anti-parallel β-barrel fold is also exploited by the fatty acid-binding proteins, which function similarly by binding small hydrophobic molecules. Similarity at the sequence level, however, is less obvious, being confined to a single short N-terminal motif.