SII-SWORD/CoKE huggingface dataset:
Zona pellucida domain (ZP_dom)
Type: Domain

The zona pellucida (ZP) domain is a protein polymerisation module of ~260 amino acid module, which is found at the C terminus of many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer . Proteins containing a ZP domain include:

Sperm receptor proteins ZP2 and ZP3. Along with protein ZP1, proteins ZP2 and ZP3 are responsible for sperm-adhesion to the zona pellucida. ZP3 first binds to specific sperm proteins, thus mediating sperm contacts with the oocyte. ZP2 acts as a second sperm receptor reinforcing the interactions. ZP1 cross-links the polymers formed by ZP2 and ZP3.

Zona pellucida sperm-binding protein B (ZP-B) (also known as ZP-X in rabbit and ZP-3 α in pig).

Glycoprotein GP2, the major component of pancreatic secretory granule membranes.

TGF-beta receptor type III (also known as betaglycan). This protein is a proteoglycan that binds to TGF-beta and could be involved in capturing and retaining TGF-beta for presentation to the signalling receptors.

Uromodulin (also known as Tamm-Horsfall urinary glycoprotein). The function of this protein, which is the most abundant in human urine, is not yet clear.

Chicken beta-tectorin, a major glycoprotein of avian tectorial membrane.

Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors .

The ZP domain contains eight strictly conserved cysteines, which form disulphide bridges. The disulphide bonds within the ZP domains are divided into two groups, suggesting that the ZP domain consists of two subdomains. In addition to the conserved cysteines, only a few aromatic or hydrophobic amino acids are absolutely invariant, probably as a result of structural rather than functional constraints .
Ionotropic glutamate receptor, metazoa (Iono_Glu_rcpt_met)
Type: Family

Ionotropic glutamate receptors (iGluRs) are a highly conserved family of ligand-gated ion channels present in animals, plants, and bacteria, which are best characterised for their roles in synaptic communication in vertebrate nervous systems . A variant subfamily of iGluRs, the Ionotropic Receptors (IRs), consist of non-glutamate-binding chemosensory receptors first identified in Drosophila melanogaster. They function in detecting odors and tastants .

There are three classes of ionotropic glutamate receptors (iGluRs): kainate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and N-methyl D-aspartate (NMDA) receptors. The NMDA receptor is highly permeable to calcium ions and plays a key role in the plasticity of synapses, which is believed to underlie memory and learning, as well as the development of the nervous system. Abnormal activation has been suggested to lead to neuronal cell death observed in many acute and chronic disorders such as ischemia, stroke, Alzheimer's disease, and Huntington's disease .

NMDA receptors possess 4 transmembrane (TM) helical domains in the C-terminal half of the sequence and require both glycine and glutamate for activation, resulting in influx of calcium ions into the cell . The receptors can also be activated by polyamine, they can be blocked by magnesium ions, inhibited by zinc ions, and modulated by arachidonic acid. Other non-NMDA glutamate receptors (e.g., kainate) are structurally similar to NMDA receptors, but are functionally distinct, possibly as a result of amino acid substitutions at important positions in the sequence.
NAD-dependent epimerase/dehydratase (Epimerase_deHydtase)
Type: Domain

This domain is found in proteins that utilise NAD as a cofactor and use nucleotide-sugar substrates for a variety of chemical reactions . One of the best studied of these proteins is UDP-galactose 4-epimerase which catalyses the conversion of UDP-galactose to UDP-glucose during galactose metabolism .
Zinc finger, PARP-type (Znf_PARP)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents PARP (Poly(ADP) polymerase) type zinc finger domains.

NAD(+) ADP-ribosyltransferase(

) is a eukaryotic enzyme that catalyses the covalent attachment of ADP-ribose units from NAD(+) to various nuclear acceptor proteins. This post-translational modification of nuclear proteins is dependent on DNA. It appears to be involved in the regulation of various important cellular processes such as differentiation, proliferation and tumour transformation as well as in the regulation of the molecular events involved in the recovery of the cell from DNA damage. Structurally, NAD(+) ADP-ribosyltransferase consists of three distinct domains: an N-terminal zinc-dependent DNA-binding domain, a central automodification domain and a C-terminal NAD-binding domain. The DNA-binding region contains a pair of PARP-type zinc finger domains which have been shown to bind DNA in a zinc-dependent manner. The PARP-type zinc finger domains seem to bind specifically to single-stranded DNA and to act as a DNA nick sensor. DNA ligase III contains, in its N-terminal section, a single copy of a zinc finger highly similar to those of PARP.
Somatostatin receptor 4 (Somatstn_rcpt_4)
Type: Family

Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) . These subtypes are widely expressed in many tissues , and frequently multiple subtypes coexist in the same cell . The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase , activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) , to voltage-dependent Ca2+ channels (SSTR1, SSTR2) , to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) .

This entry represents SSTR4. It is present in high levels in the pituitary, but is less abundant in the brain and peripheral tissues . All five human somatostatin receptors expressed in COS-7 cells are coupled to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 .
Adenosine A2A receptor (Adeno_A2A_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

In addition to their role in energy metabolism, purines (especially adenosine and adenine nucleotides) produce a wide range of pharmacological effects mediated by activation of cell surface receptors. Distinct receptors exist for adenosine. In the periphery, the main effects of adenosine include vasodilation, bronchoconstriction, immunosuppresion, inhibition of platelet aggregation, cardiac depression, stimulation of nociceptive afferents, inhibition of neurotransmitter release and inhibition of the release of other factors, e.g. hormones. In the CNS, adenosine exerts a pre- and post-synaptic depressant action, reducing motor activity, depressing respiration, inducing sleep and relieving anxiety. The physiological role of adenosine is thought to be to adjust energy demands in line with oxygen supply. Many of the clinical actions of methylxanthines are thought to be mediated through antagonism of adenosine receptors. Four subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

A2A receptors have a limited distribution in the brain and are found in the striatum, olfactory tubercle and nucleus accumbens. In the periphery, A2 receptors mediate vasodilation, immunosuppression, inhibition of platelet aggregation and gluconeogenesis. The receptors activate adenylyl cyclase through G proteins.
DNA-directed RNA polymerase, 30-40kDa subunit, conserved site (DNA-dir_RNA_pol_30-40kDasu_CS)
Type: Conserved_site

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

In archaebacteria, there is generally a single form of RNA polymerase which also consist of an oligomeric assemblage of 10 to 12 polypeptides.
It has been shown that small subunits of about 30 to 40kDa found in archebacterial and all three types of eukaryotic polymerases are highly conserved. Subunits known to belong to this family are:

Saccharomyces cerevisiae RPC5 subunit (or RPC40) from RNA polymerases I and III.

Mammalian RPA40 from RNA polymerase I.

S. cerevisiae RPB3 subunit from RNA polymerase II.

Schizosaccharomyces pombe rpb3 subunit from RNA polymerase II.

Mammalian RPB3 (or RPB33) (gene POLR2C) from RNA polymerase II.

Conjugation stage-specific protein cnjC from Tetrahymena thermophila, which may be a stage-specific RNA polymerase subunit.

Archaebacterial RNA polymerase subunit D (gene rpoD).
Large ribosomal subunit protein eL32 (Ribosomal_eL32)
Type: Family

eL32 is a protein from the large ribosomal subunit that contains a surface-exposed globular domain and a finger-like projection that extends into the RNA core to stabilize the tertiary structure. eL32 does not appear to play a role in forming the A (aminacyl), P (peptidyl) or E (exit) sites of the ribosome, but does interact with 23S rRNA, which has a "kink-turn" secondary structure motif. eL32 is overexpressed in human prostate cancer and has been identified as a stably expressed housekeeping gene in macrophages of human chronic obstructive pulmonary disease (COPD) patients. In Schizosaccharomyces pombe, eL32 has also been suggested to play a role as a transcriptional regulator in the nucleus. Found in archaea and eukaryotes .

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 .
NADH-Ubiquinone oxidoreductase (complex I), chain 5 N-terminal (Proton_antipo_N)
Type: Domain

Mrp-type antiporters comprise the cation/proton antiporter family 3 (CPA3), commonly referred to as Mrp. They are the products of operons that carry either six or seven genes (mrpA-G), and form complexes containing all subunits . They have Na(+)/H(+) antiporter activity . Two of the Mrp proteins, MrpA and MrpD, resemble NuoL/ND5, NuoM/ND4, NuoN/ND2, the homologous subunits that constitute the membrane-embedded, proton-translocating core of complex I . They also resemble subunits of membrane-bound hydrogenases, such as HyfB, HyfD and HyfF from E.coli and F420H2 dehydrogenasa (FPO complex) subunits L, N and M .

This domain represents an N-terminal extension of

. It is found in complex I subunit NuoL/ND5, CPA3 antiporters subunit MrpA, and in F(420)H(2) dehydrogenase subunit L.
Only NADH-Ubiquinone chain 5 and eubacterial chain L are in this family. This sub-family is part 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.
Luteovirus group 1 coat protein (Luteo_coat)
Type: Family

Barley yellow dwarf virus (BYDV) can be separated into two groups based on serological relationships, presumably governed by the viral capsid structure . Coding regions of coat proteins have been identified for the MAV-PS1, P-PAV (group 1) and NY-RPV (group 2) isolates of BYDV. Group 1 proteins show 71% sequence similarity to each other, 51% similarity to those of group 2, and a high degree of similarity to those from other luteoviruses (including coat proteins from Beet western yellows virus (BWYV) and Potato leafroll virus (PLrV) ).

Among luteovirus coat protein sequences in general, several highly conserved domains can be identified, while other domains differentiate group 1 isolates from group 2 and other luteoviruses. Sequence comparisons between the genomes of PLrV, BWYV and BYDV have revealed ~65% protein sequence similarity between the capsid proteins of BWYV and PLrV and ~45% similarity between BYDV and PLrV . The N-terminal regions of these sequences, like those of many plant virus capsid proteins, is highly basic. These regions may be involved in protein-RNA interaction.
Argininosuccinate synthase (Arginosuc_synth)
Type: Family

Argininosuccinate synthase (

) (AS) is a urea cycle enzyme that catalyses the penultimate step in arginine biosynthesis: the ATP-dependent ligation of citrulline to aspartate to form argininosuccinate, AMP and pyrophosphate .

In humans, a defect in the AS gene causes citrullinemia, a genetic disease characterised by severe vomiting spells and mental retardation.

AS is a homotetrameric enzyme of chains of about 400 amino-acid residues. An arginine seems to be important for the enzyme's catalytic mechanism. The sequences of AS from various prokaryotes, archaebacteria and eukaryotes show significant similarity.
Ferritin (Ferritin)
Type: Family

Ferritin is one of the major non-haem iron storage proteins in animals, plants, and microorganisms . It consists of a mineral core of hydrated ferric oxide, and a multi-subunit protein shell which encloses the former and assures its solubility in an aqueous environment.

In animals the protein is mainly cytoplasmic and there are generally two or more genes that encode closely related subunits (in mammals there are two subunits which are known as H(eavy) and L(ight)). In plants ferritin is found in the chloroplast .
5-Hydroxytryptamine 4 receptor (5HT4_rcpt)
Type: Family

5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics .

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel , all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family , and they activate an intracellular second messenger cascade to produce their responses.

The 5-HT4 receptor functions in both the peripheral and central nervous system, and is involved in modulating the release of various neurotransmitters. In addition to adenylyl cyclase stimulation, direct coupling to potassium channels and voltage sensitive calcium channels have been proposed as postreceptor events . The 5HT4 receptor is located in neurons in the CNS, with highest levels in colliculus and hippocampus , it has not been found in the cerebellum . In the CNS, the receptor enhances synaptic transmission , and they may also play a role in learning, memory and appetite . In the periphery, it is found in the alimentary tract, urinary bladder, heart and adrenal gland .
Opsin, blue sensitive (Opsin_blue)
Type: Family

Opsins are the photoreceptors of animal retinas: vertebrate rhodopsin is found in rod cells and mediates scotopic vision; red, green and blue opsins are found in cone cells and mediate photopic vision. Blue-sensitive opsin has an absorption maximum at 420nm. The ratio of blue cones to rods is ~1:200. Deficiency in blue opsin results in tritanopia colour blindness.