SII-SWORD/CoKE huggingface dataset:
Neuromodulin, palmitoylation site (Neuromodulin_palmitoyl_site)
Type: PTM

This entry represents the N-terminal in Neuromodulin which contains two cysteine residues that are palmitoylated and are responsible for the attachment of the protein to the membrane.

Neuromodulin (also known as growth-associated protein 43 or GAP-43) is a component of the motile growth cones. It is membrane protein whose expression is widely correlated with successful axon elongation . It is a crucial component of an effective regeneration response in the nervous system . Although its function is uncertain, the N-terminal region is well conserved and contains both a calmodulin binding domain, and sites for acylation, membrane attachment and protein kinase C phosphorylation. Structure predictions suggest that the C-terminal region may exist as an extended, negatively-charged rod with some similarity to the side arms of neurofilaments, indicating that the biological role of neuromodulin may depend on its ability to form a dynamic membrane-cytoplasm-calmodulin complex .
Allergen V5/Tpx-1-related, conserved site (Allrgn_V5/Tpx1_CS)
Type: Conserved_site

The cysteine-rich secretory proteins (Crisp) are predominantly found in the mammalian male reproductive tract as well as in the venom of reptiles. This family includes mammalian testis-specific protein (Tpx-1), also known as cysteine-rich secretory protein 2 (CRISP2) ; venom allergen 5 from vespid wasps and venom allergen 3 from fire ants, which are potent allergens that mediate allergic reactions to stings insects of the Hymenoptera family ; scoloptoxins from Scolopendra dehaani (Thai centipede) ; plant pathogenesis proteins of the PR-1 family , which are synthesised during pathogen infection or other stress-related responses; allurin, a sperm chemoattractant , serotriflin , etc.

The precise function of some of these proteins is still unclear. Tpx-1 or CRISP2 may regulate some ion channels' activity and thereby regulate calcium fluxes during sperm capacitation .

This entry also includes allergen Tab y 5.0101 from horsefly salivary glands .
Gonadotropin, beta subunit, conserved site (Gonadotropin_bsu_CS)
Type: Conserved_site

The crystal structures of four growth factors; nerve growth factor, transforming growth factor-beta, platelet-derived growth factor, and human chorionic gonadotropin from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology . These proteins show very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers . Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organisation increases the variety of structures built around this simple structural motif .

Glycoprotein hormones (or gonadotropins) are a family of proteins which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin (TSH) and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. All these hormones consist of two glycosylated chains (alpha and beta). In mammalian gonadotropins, the alpha chain is identical in the four types of hormones but the beta chains, while homologous, are different.

The beta chains are proteins of about 100 to 140 amino acid residues which contain the cysteine-knot domain , as shown in the following schematic representation.

+----------------------+
| +------------|-----------------------------+
| +-|------------|--------+ |
| | | | | |
xxxCxxxxxxxCxCxxCxCxxxxxxxCxxxxxxxxCxxxxxxxCxCxCxxCxxxxxCxxxxxxxxxxx
| | | | | |
| | | | +--+
+-|------------------------+ |
+--------------------------+

'C': conserved cysteine involved in a disulphide bond.
AP endonuclease 2, zinc binding site (AP_endonuc_F2_Zn_BS)
Type: Binding_site

Cellular DNA is spontaneously and continuously damaged by environmental and internal factors such as X-rays, UV light and agents such as the antitumor drugs bleomycin and neocarzinostatin or those that generate oxygen radicals. Apurinic/apyrimidinic (AP) sites can form spontaneously or as highly cytotoxic intermediates in the removal of the damaged base by the base excision repair (BER) pathway. 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. Family 2 groups the enzymes listed below .

Bacterial endonuclease IV (

).

Mycobacterium leprae probable endonuclease .

Saccharomyces cerevisiae (Baker's yeast) apurinic endonuclease APN1 (

).

Caenorhabditis elegans hypothetical protein APN-1 or T05H10.2.

APN1 and endonuclease IV have been shown to be transition metalloproteins that bind three zinc ions . The metal-binding sites have been determined from the 3D-structure of Escherichia coli endonuclease IV , which shows an α/β-barrel fold similar to that of other divalent metal-dependent TIM barrel enzymes, such as xylose isomerase.
EF-Hand 1, calcium-binding site (EF_Hand_1_Ca_BS)
Type: Binding_site

This entry represents the complete EF-hand loop as well as the first residue which follows the loop and which seem to always be hydrophobic. Interestingly, positions 1 (X), 3 (Y) and 12 (-Z) are the most conserved. The 6th residue in an EF-hand loop is, in most cases a Gly, but the number of exceptions to this 'rule' has gradually increased, therefore, this signature pattern includes all the different residues which have been shown to exist in this position in functional Ca-binding sites. The pattern is known, in some cases, to miss one of the EF-hand regions in some proteins with multiple EF-hand domains.

Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue α-helical domain. In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). Ca2 binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers .
Neuregulin-1 (NRG1)
Type: Family

Neuregulins (NRG) are a sub-family of EGF-like molecules that have been shown to play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses . Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor . Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.

The transmembrane forms of neuregulin 1 (NRG1) are present within synaptic vesicles, including those containing glutamate . After exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit expression, localisation, and /or phosphorylation facilitating subsequent glutamate transmission. Membrane-anchored Nrg-1 isoforms consist of a variable N-terminal extracellular domain and a conserved transmembrane and C-terminal cytoplasmic domains .
Crustacean neurohormone, conserved site (Crust_neurhormone_CS)
Type: Conserved_site

Arthropod express a family of neuropeptides which so far consist of the following types of neurohormones:

Crustacean hyperglycemic hormone (CHH). CHH is primarily involved in blood sugar regulation, but also plays a role in the control of molting and reproduction.

Molt-inhibiting hormone (MIH). MIH inhibits Y-organs where molting hormone (ecdysteroid) is secreted. A molting cycle is initiated when MIH secretion diminishes or stops.

Gonad-inhibiting hormone (GIH), also known as vitellogenesis-inhibiting hormone (VIH) because of its role in inhibiting vitellogenesis in female animals.

Mandibular organ-inhibiting hormone (MOIH). MOIH represses the synthesis of methyl farnesoate, the precursor of insect juvenile hormone III in the mandibular organ.

Ion transport peptide (ITP) from locust. ITP stimulates salt and water reabsorption and inhibits acid secretion in the ileum of the locust.

These neurohormones are peptides of 70 to 80 residues which are processed from larger size precursors. They contain six conserved cysteines that are involved in disulphide bonds, as shown in the following schematic representation.
Annexin repeat, conserved site (Annexin_repeat_CS)
Type: Conserved_site

Annexins are a group of calcium-binding proteins that associate reversibly with membranes. They bind to phospholipid bilayers in the presence of micromolar free calcium concentration. The binding is specific for calcium and for acidic phospholipids. Annexins have been claimed to be involved in cytoskeletal interactions, phospholipase inhibition, intracellular signaling, anticoagulation, and membrane fusion. Annexins are widely distributed among eukaryotes but largely absent in prokaryotes and yeast. They are classified according to the evolutionary divisions of the eukaryotes into five families: A (ANXA, vertebrates, including humans), B (ANXB, invertebrates), C (ANXC, fungi), D (ANXD, true plants), E (ANXE, protists).

Each of these proteins consist of a unique N-terminal domain followed by four or eight copies (in annexin A6) of a conserved segment of approximately 70 residues. The tertiary structure of annexins is evolutionary conserved; a single molecule resembles a slightly curved disk with the calcium and phospholipid-binding sites located on the more convex surface and the more concave surface facing the cytoplasm. Each single annexin repeat (sometimes known as an 'endonexin fold') is comprised of five α-helices(A-E). Four of them (A, B, D and E) are arranged parallel and form a tightly packed helix-loop-helix bundle. In contrast, helix C is almost perpendicular and covers the remaining four on the surface. Each of the
repeats has the potential to have a type II Ca(2)-binding bipartite motif, located on two different α-helices (GxGT-(38-40 residues)-D/E), but
typically some of them are non-functional. The core of the helix bundle is composed largely of hydrophobic residues, while hydrophilic residues are
exposed on the surface of the protein and between the repeats. The N-terminal domain of variable length, amino acid composition, and determinants of hydrophobicity plays an important role in mediating the interaction of annexins with other intracellular protein partners, such as those of the S100
family cytoplasmic proteins .

This region spans positions 9 to 61 of the repeat and includes the only perfectly conserved residue (an arginine in position 22).
Large ribosomal subunit protein uL29, conserved site (Ribosomal_uL29_CS)
Type: Conserved_site

Ribosomal protein uL29 is one of the proteins from the large ribosomal subunit. uL29 belongs to a family of ribosomal proteins of 63 to 138 amino-acid residues which, on the basis of sequence similarities, groups:

Red algal uL29.

Bacterial uL29.

Mammalian uL29 (known as L35)

Caenorhabditis elegans uL29 (known as L35) (ZK652.4).

Yeast uL29 (known as L35).

uL29 is located on the surface of the large ribosomal subunit, where it participates in forming a protein ring that surrounds the polypeptide exit channel, providing structural support for the ribosome . uL29 is involved in forming the translocon binding site, along with L19, L22, L23, L24, and L31e. In addition, uL29 and L23 form the interaction site for trigger factor (TF) on the ribosomal surface, adjacent to the exit tunnel . uL29 forms numerous interactions with L23 and with the 23S rRNA.

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 .
Large ribosomal subunit protein uL16, conserved site, eukaryotes/archaea (Ribosomal_uL16_CS_euk_arc)
Type: Conserved_site

This entry represents a conserved site found in the central region of the large ribosomal subunit protein uL16 from archaea and eukaryotes (in the latter were previously known as L10) .

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 .
Large ribosomal subunit protein eL13, conserved site (Ribosomal_eL13_CS)
Type: Conserved_site

This entry represents the ribosomal protein eL13 found in vertebrates , fruit fly, plants, yeast, amongst other eukaryotes and archaea.

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 .
Large ribosomal subunit protein bL19, conserved site (Ribosomal_bL19_CS)
Type: Conserved_site

This entry represents a conserved region found at the C-terminal of the large ribosomal subunit protein bL19 from bacteria Red algal chloroplast (bL19c) and cyanelle . In Escherichia coli, bL19 is known to be located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site.

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 .