SII-SWORD/CoKE huggingface dataset:
Protein-tyrosine phosphatase, low molecular weight, mammalian (Tyr_Pase_low_mol_wt_mml)
Type: Family

This entry represents mammalian low molecular weight (LMW) phosphotyrosine protein phosphatase (or acid phosphatase), which act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates . The structure of a LMW PTPase has been solved by NMR . It belongs to the α/β class, with 6 α-helices and 4 β-strands forming a 3-layer α-β-α sandwich architecture.

Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;

) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation . The PTP superfamily can be divided into four subfamilies :

(1) pTyr-specific phosphatases

(2) dual specificity phosphatases (dTyr and dSer/dThr)

(3) Cdc25 phosphatases (dTyr and/or dThr)

(4) LMW (low molecular weight) phosphatases

Based on their cellular localisation, PTPases are also classified as:

Receptor-like, which are transmembrane receptors that contain PTPase domains

Non-receptor (intracellular) PTPases

All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif . Functional diversity between PTPases is endowed by regulatory domains and subunits.
Melittin/ Api allergen (Melittin/Api_allergen)
Type: Family

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 3.

Melittin is the principal protein component of the venom of the honeybee, Apis mellifera. It inhibits protein kinase C, Ca
2+
/calmodulin-dependent protein kinase II, myosin light chain kinase and Na
+
/K
+
-ATPase (synaptosomal membrane) and is a cell membrane lytic factor. Melittin is a small peptide with no disulphide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic.

The molecular mechanisms underlying the various effects of melittin on membranes have not been completely defined and much of the evidence indicates that different molecular mechanisms may underlie different actions of the peptide .

Extensive work with melittin has shown that the venom has multiple effects, probably, as a result of its interaction with negatively changed phospholipids. It inhibits well known transport pumps such as the Na
+
-K
+
-ATPase and the H
+
-K
+
-ATPase. Melittin increases the permeability of cell membranes to ions, particularly Na
+
and indirectly Ca
2+
, because of the Na
+
-Ca
2+
-exchange. This effect results in marked morphological and functional changes, particularly in excitable tissues such as cardiac myocytes. In some other tissues, e.g., cornea, not only Na
+
but Cl- permeability is also increased by melittin. Similar effects to melittin on H
+
-K
+
-ATPase have been found with the synthetic amphipathic polypeptide Trp-3 .

The study of melittin in model membranes has been useful for the development of methodology for determination of membrane protein structures. A molecular dynamics simulation of melittin in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer was carried out. The effect of melittin on the surrounding membrane was localised to its immediate vicinity, and its asymmetry with respect to the two layers may be a result of the fact that it is not fully transmembranal. Melittin's hydrophilic C terminus anchors it at the extracellular interface, leaving the N terminus "loose" in the lower layer of the membrane .
p53 tumour suppressor family (p53_tumour_suppressor)
Type: Family

This entry also includes the p53 family members p63 , p73 and transcription factor cep-1 .

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.
Histone H2A (Histone_H2A)
Type: Family

Histone H2A is a small, highly conserved nuclear protein that, together with two molecules each of histones H2B, H3 and H4, forms the eukaryotic nucleosome core ; the nucleosome octamer winds ~146 DNA base-pairs. In the mouse, histone H2A can be replaced by histone H2A-like 1 .
Thyrotropin-releasing hormone receptor (TRH_rcpt_1)
Type: Family

Thyrotropin-releasing hormone, also known as thyroliberin (TRH) stimulates the synthesis and release of thyroid-stimulating hormone in the anterior pituitary . TRH is produced in many other tissues, especially within the nervous system, where it appears to act as a neurotransmitter/neuromodulator. It also stimulates the synthesis and release of prolactin . In the CNS, TRH stimulates a number of behavioural and pharmacological actions, including increased turnover of catecholamines in the nucleus accumbens . TRH initiates all of these effects by interacting with receptors that belong to a class of G protein-coupled receptors, rhodopsin-type (GPCRA) .

There are two thyrotropin-releasing hormone receptors, thyrotropin-releasing hormone receptor (TRH1) which has been found in a number of species including rat, mouse and human and thyrotropin-releasing hormone receptor 2 (TRH2) which has, only been found in rodents . These TRH receptors are found in high levels in the anterior pituitary, and are also found in the retina and in certain areas of the brain . The receptors activate phosphoinositide metabolism through a pertussis-toxin-insensitive G-protein, probably of the Gq/G11 class .

This entry represents the thyrotrophin-releasing hormone receptor.
HRDC domain (HRDC_dom)
Type: Domain

The HRDC (helicase and RNaseD C-terminal) domain is comprised of two orthogonally packed α-hairpin subdomains, and is involved in interactions with DNA and protein. It has been suggested that this domain plays a role dissolving double Holliday junctions efficiently .

HRDC domains are found at the C terminus of many RecQ helicases, including the human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN and RecQ-like DNA helicase BLM . RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. The structure of the HRDC domain consists of a 4-5 helical bundle of two orthogonally packed α-hairpins, and as such it resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. A positively charged region on the surface of the HRDC domain is able to interact with DNA.

The HRDC domain is also present in eukaryotic and archaeal RNA polymerase II subunit RBP4, the N-terminal of which forms a heterodimerisation α-hairpin .

The HRDC domain has a putative role in nucleic acid binding. Mutations in the HRDC domain associated with the human BLM gene result in Bloom Syndrome (BS), an autosomal recessive disorder characterised by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability .
Phospholipid/glycerol acyltransferase (Plipid/glycerol_acylTrfase)
Type: Domain

This family is found in diverse acyltransferases involved in phospholipid biosynthesis . This domain is found in tafazzins, phospholipid transacylases involved in the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation and whose defects cause of Barth syndrome; a severe inherited disorder which is often fatal in childhood and is characterised by cardiac and skeletal abnormalities . Phospholipid/glycerol acyltransferase is not found in the viruses or the archaea and is under represented in the bacteria. Bacterial glycerol-phosphate acyltransferases are involved in membrane biogenesis since they use fatty acid chains to form the first membrane phospholipids .
Cytochrome c oxidase, subunit Vb (Cyt_c_oxidase_su5b)
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, there are a variable number of small polypeptidic subunits. One of these subunits, which is known as Vb in mammals, V in Dictyostelium discoideum (Slime mold) and IV in yeast, binds a zinc atom. The sequence of subunit Vb is well conserved and includes three conserved cysteines that coordinate the zinc ion . Two of these cysteines are clustered in the C-terminal section of the subunit.
Cytidine and deoxycytidylate deaminase domain (CMP_dCMP_dom)
Type: Domain

Cytidine deaminase (

) (cytidine aminohydrolase) catalyses the hydrolysis of cytidine into uridine and ammonia while deoxycytidylate
deaminase (

) (dCMP deaminase) hydrolyses dCMP into dUMP. Both enzymes are known to bind zinc and to require it for their catalytic activity . The deaminases possess either one or two conserved zinc-coordinating (Z) motifs, with the consensus amino acid signature H-x(1)-E-x(24,28)-P-C-x(2,4)-C. This motif is required for catalytic activity. Zinc coordination is mediated by a histidine and two cysteines . The CMP/dCMP-type deaminase domain consists of a central β-sheet with one or more α-helices on each side .

This entry represents the CMP/dCMP-type deaminase domain. Some enzymes, such as riboflavin biosynthesis protein PYRR, have a non-functional deaminase domain that lacks the catalytically essential zinc-binding residues .
Cadherin-like (Cadherin-like_dom)
Type: Domain

This entry represents the extracellular repeated domains found in cadherins and related proteins.

Cadherins are a group of transmembrane proteins that serve as the major adhesion molecules located within adherens junctions. They can regulate cell-cell adhesion through their extracellular domain and their cytosolic domains connect to the actin cytoskeleton by binding to catenins . These proteins preferentially interact with themselves in a homophilic manner in connecting cells; thus acting as both receptor and ligand. They may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins.

Structurally, cadherins comprise a number of domains: classically, these include a signal sequence; a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated extracellular cadherin domains, 4 of which are cadherin repeats, and the fifth contains 4 conserved cysteines and a C-terminal cytoplasmic domain . However, proteins are designated as members of the broadly defined cadherin family if they have one or more cadherin repeats. A cadherin repeat is an independently folding sequence of approximately 110 amino acids that contains motifs with the conserved sequences DRE, DXNDNAPXF, and DXD. Crystal structures have revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved Ca2+-binding pocket at the domain-domain interface. Cadherins depend on calcium for their function: calcium ions bind to specific residues in each cadherin repeat to ensure its proper folding, to confer rigidity upon the extracellular domain and is essential for cadherin adhesive function and for protection against protease digestion.
NADH:ubiquinone/plastoquinone oxidoreductase, chloroplast chain 5, C-terminal (NADH_UbQ_OxRdtase_chlpt_su5_C)
Type: Domain

This domain represents a C-terminal extension of NADH-Ubiquinone/plastoquinone (complex I) chains (see

). Chain 5 is a component of complex I which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane .
Pyridoxal phosphate-dependent decarboxylase (PyrdxlP-dep_de-COase)
Type: Family

A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group . Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine ; tyrosine decarboxylase, which converts tyrosine into tyramine; histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine ; L-aspartate decarboxylase, which converts aspartate to beta-alanine ; and phenylacetaldehyde synthase that catalyses the decarboxylation of L-phenylalanine to 2-phenylethylamine . These enzymes belong to the group II decarboxylases .

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .
Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain (Cyclophilin-type_PPIase_dom)
Type: Domain

Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity (

), accelerating protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides . They also have protein chaperone-like functions and are the major high-affinity binding proteins for the immunosuppressive drug cyclosporin A (CSA) in vertebrates .

Cyclophilins are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function . They share a common 109 amino acid cyclophilin-like domain (CLD) and additional domains unique to each member of the family. The CLD domain contains the PPIase activity, while the unique domains are important for selection of protein substrates and subcellular compartmentalisation .

This entry represents the core β-barrel cyclophilin-like domain.
Glycoprotein hormone receptor family (Gphrmn_rcpt_fam)
Type: Family

Glycoprotein hormones (or gonadotropins) are protein hormones, that includes the mammalian hormones follicle-stimulating hormone (FSH, also known as follitropin), luteinizing hormone (LH, also known as lutropin), thyroid-stimulating hormone (TSH, also known as thyrotropin) and human chorionic gonadotropin (hCG). These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function . The hormones FSH, LH and TSH are secreted by the anterior pituitary gland , while the choriogonadotropins are secreted by the placenta .

Glycoprotein hormone receptors are members the rhodopsin-like G-protein coupled receptor (GPCR) family. They function as receptors for the pituitary hormones thyrotropin (TSH receptor), follitropin (FSH receptor) and lutropin (LH receptor). In mammals the LH receptor is also the receptor for the placental hormone, human chorionic gonadotropin (hCG), so is denominated as a lutropin-choriogonadotropic hormone receptor (LHCG receptor). The receptors share close sequence similarity, and are characterised by large extracellular domains believed to be involved in hormone binding via leucine-rich repeats (LRR) .

This entry represents the glycoprotein hormone receptor family, which includes the follicle stimulating hormone receptor, lutropin-choriogonadotropic hormone receptor and the thyroid stimulating hormone receptor.
Large ribosomal subunit protein uL5 (Ribosomal_uL5)
Type: Family

Large ribosomal subunit protein uL5, previously known as Ribosomal protein L5, is ~180 amino acids in length. In Escherichia coli, uL5 is known to be involved in binding 5S RNA to the large ribosomal subunit .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
S-adenosylmethionine synthetase (S-AdoMet_synthetase)
Type: Family

S-adenosylmethionine synthetase (MAT,

) is the enzyme that catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP . AdoMet is an important methyl donor for transmethylation and is also the propylamino donor in polyamine biosynthesis.

In bacteria there is a single isoform of AdoMet synthetase (gene metK), there are two in budding yeast (genes SAM1 and SAM2) and in mammals while in plants there is generally a multigene family.

The sequence of AdoMet synthetase is highly conserved throughout isozymes and species. The active sites of both the Escherichia coli and rat liver MAT reside between two subunits, with contributions from side chains of residues from both subunits, resulting in a dimer as the minimal catalytic entity. The side chains that contribute to the ligand binding sites are conserved between the two proteins. In the structures of complexes with the E. coli enzyme, the phosphate groups have the same positions in the (PPi plus Pi) complex and the (ADP plus Pi) complex and are located at the bottom of a deep cavity with the adenosyl group nearer the entrance .
Histidine-rich calcium-binding repeat (His-rich_Ca-bd_rpt)
Type: Repeat

The histidine-rich calcium-binding protein (HCP) of sarcoplasmic reticulum may play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle. This protein is very acidic (31% of Asp and Glu) and rich in histidine (13%). The sequence of HCP contains 10 tandem repeats of a 26 to 29 amino acid residues domain. This domain starts with an invariant hexapeptide (HRHRGH), followed by a stretch of acidic residues. The end of the domain consist of an almost invariant nonapeptide (STESDRHQA). The highly acidic central cores of each repeat are likely to constitute the calcium-binding sites of HCP.