SII-SWORD/CoKE huggingface dataset:
Zinc finger, PHD-type (Znf_PHD)
Type: Domain

This entry represents the PHD (homeodomain) zinc finger domain , which is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The PHD finger motif is reminiscent of, but distinct from the C3HC4 type RING finger.

The function of this domain is not yet known but in analogy with the LIM domain it could be involved in protein-protein interaction and be important for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. Alternatively, the interactions could be intra-molecular and be important in maintaining the structural integrity of the protein. In similarity to the RING finger and the LIM domain, the PHD finger is thought to bind two zinc ions.

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.
Sodium/hydrogen exchanger 1-like (NHE-1-like)
Type: Family

Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers . These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia . Human NHE is also involved in heart disease, cell growth and in cell differentiation . The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) . These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport .

Sodium/hydrogen exchanger 1 (NHE-1) is found in virtually all tissues and cells in mammals and is involved in numerous physiological processes, including regulation of intracellular pH, cellular volume, cytoskeletal organisation, heart disease and cancer . In epithelial cells, NHE-1 is largely restricted to the basolateral membrane, which specific subcellular localisation is thought to be important to the functioning of these epithelia. This protein comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions.

NHE-1 plays a role in survival and migration and invasion of several cancers . It was shown to be activated at physiological levels of NO .
Small ribosomal subunit protein uS11 (Ribosomal_uS11)
Type: Family

Small ribosomal subunit protein uS11, previously known as Ribosomal protein S11 , plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small 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 .
Stomatin/HflK family (Stomatin_HflK_fam)
Type: Family

This entry includes human Stomatin, bacterial HflK and similar proteins from all cellular organisms.

The band-7 protein family comprises a diverse set of membrane-bound proteins characterised by the presence of a conserved domain, the band-7 domain, also known as SPFH or PHB domain. The exact function of the band-7 domain is not known, but examples from animal and bacterial stomatin-type proteins demonstrate binding to lipids and the ability to assemble into membrane-bound oligomers that form putative scaffolds .

A variety of proteins belong to the band-7 family. These include the stomatins, prohibitins, flottins and the HflK/C bacterial proteins. Eukaryotic band 7 proteins tend to be oligomeric and are involved in membrane-associated processes. Stomatins are involved in ion channel function, prohibitins are involved in modulating the activity of a membrane-bound FtsH protease and the assembly of mitochondrial respiratory complexes, and flotillins are involved in signal transduction and vesicle trafficking .

Stomatin, also known as human erythrocyte membrane protein band 7.2b , was first identified in the band 7 region of human erythrocyte membrane proteins. It is an oligomeric, monotopic membrane protein associated with cholesterol-rich membranes/lipid rafts. Human stomatin is ubiquitously expressed in all tissues; highly in hematopoietic cells, relatively low in brain. It is associated with the plasma membrane and cytoplasmic vesicles of fibroblasts, epithelial and endothelial cells .

Stomatin is believed to be involved in regulating monovalent cation transport through lipid membranes. Absence of the protein in hereditary stomatocytosis is believed to be the reason for the leakage of Na
+
and K
+
ions into and from erythrocytes . Stomatin is also expressed in mechanosensory neurons, where it may interact directly with transduction components, including cation channels .

Stomatin proteins have been identified in various organisms, including Caenorhabditis elegans. There are nine stomatin-like proteins in C. elegans, MEC-2 being the one best characterised . In mammals, other stomatin family members are stomatin-like proteins SLP1, SLP2 and SLP3, and NPHS2 (podocin), which display selective expression patterns . Stomatin family members are oligomeric, they mostly localise to membrane domains, and in many cases have been shown to modulate ion channel activity.

The stomatins and prohibitins, and to a lesser extent flotillins, are highly conserved protein families and are found in a variety of organisms ranging from prokaryotes to higher eukaryotes, whereas HflK and HflC homologues are only present in bacteria .
P2Y6 purinoceptor (P2Y6_rcpt)
Type: Family

There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides , known as P1, P2X and P2Y purinoceptors . These receptors induce a wide variety of biological effects and are involved in many different cellular functions . P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors . The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine , P2X via ATP , whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) .

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 . P2Y3 has, as yet, only been found in birds , whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) .

This entry represents P2Y6 receptor. The receptor displays pharmacological characteristics distinct from any other P2Y receptor subtype, having a preference for uridine nucleotides, with UDP being 100-fold more potent than UTP. It associates weakly with ADP, but it is not responsive to ATP . P2Y6 is abundantly expressed in various tissues, including the spleen, placenta, kidney, adipose, bone, lung, heart, brain and skeletal muscle . In mouse bone marrow-derived mast cells and in the human cell line LAD2, P2Y6 receptors cooperate with cysteinyl leukotriene receptor 1 to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk . In human, rat and mouse, P2Y6 expression is increased by the stress associated with intestinal inflammation, leading to the release of CXC chemokine ligand 8 by an ERK1/2-dependent mechanism .
Large ribosomal subunit protein eL40 domain (Ribosomal_eL40_dom)
Type: Domain

This entry represents the L40 ribosomal domain from both archaea and eukaryotes.

In eukaryotes, L40 is fused to ubiquitin moieties, and this fusion protein is known as Ubiquitin-ribosomal protein eL40 fusion protein or UBL40 . Specific endopeptidases cleave these precursor molecules to release ubiquitin moieties . UBL40 plays important roles in gametogenesis . This fusion may also have a pre-cleavage function in ribosome assembly . In Saccharomyces cerevisiae, eL40 is essential for translation of a subset of cellular transcripts, including stress response transcripts, such as DDR2 . In humans, it has been reported to be required for cap-dependent translation of vesicular stomatitis virus mRNAs .

In archaea and some eukaryotic species such as Candida albicans, this domain covers the whole length of the protein, which is known as Large ribosomal subunit protein eL40 .

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 .
Small ribosomal subunit protein eS24 (Ribosomal_eS24)
Type: Family

This family contains the eS24 ribosomal proteins from eukaryotes and archaebacteria. These proteins have 101 to 148 amino acids.

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 .
Dephospho-CoA kinase (Depp_CoAkinase)
Type: Family

This family contains Dephospho-coenzyme A kinase (DPCK,

), which catalyzes the final step in dephosphocoenzyme A (dCoA) biosynthesis, the phosphorylation of the 3'-hydroxyl group of ribose using ATP as a phosphate donor.

The crystal structures of a number of the proteins in this entry have been determined, including the structure of the protein from Haemophilus influenzae to 2.0-A resolution in a comlex with ATP. The protein consists of three domains: the nucleotide-binding domain with a five-stranded parallel β-sheet, the substrate-binding α-helical domain, and the lid domain formed by a pair of α-helices; the overall topology of the protein resembles the structures of other nucleotide kinases .
Troponin (Troponin)
Type: Family

The troponin (Tn) complex regulates Ca
2+
induced muscle contraction. Tn contains three subunits, Ca
2+
binding (TnC), inhibitory (TnI), and tropomyosin binding (TnT). This family includes troponin T and troponin I. Troponin I binds to actin and troponin T binds to tropomyosin .
Phosphopantetheine adenylyltransferase (PPAT)
Type: Family

Phosphopantetheine adenylyltransferase (PPAT;

) is an essential enzyme in bacteria, responsible for catalyzing the rate-limiting step in coenzyme A (CoA) biosynthesis: catalysis of the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine to give dephospho-CoA (DPCOA) and pyrophosphate in the fourth (and penultimate) step of coenzyme A biosynthesis . The dinucleotide-binding fold of PPAT is homologous to class I aminoacyl-tRNA synthetases . CoA has been shown to inhibit PPAT and competes with ATP, PhP, and dPCoA. PPAT is a homohexamer in E. coli .

The enzyme had previously been thought to have a role in lipopolysaccharide biosynthesis .
Colipase (Colipase)
Type: Family

Colipase is a small protein cofactor needed by pancreatic lipase for efficient dietary lipid hydrolyisis. It also binds to the bile-salt covered triacylglycerol interface, thus allowing the enzyme to anchor itself to the water-lipid interface. Efficient absorption of dietary fats is dependent on the action of pancreatic triglyceride lipase. Colipase binds to the C-terminal, non-catalytic domain of lipase, thereby stabilising as active conformation and considerably increasing the overall hydrophobic binding site. Structural studies of the complex and of colipase alone have revealed the functionality of its architecture .

Colipase is a small protein with five conserved disulphide bonds. Structural analogies have been recognised between a developmental protein (Dickkopf), the pancreatic lipase C-terminal domain, the N-terminal domains of lipoxygenases and the C-terminal domain of alpha-toxin. These non-catalytic domains in the latter enzymes are important for interaction with membrane. It has not been established if these domains are also involved in eventual protein cofactor binding as is the case for pancreatic lipase .
S-adenosylmethionine decarboxylase, eukaryotes (S-AdoMet_decarboxylase_euk)
Type: Family

This entry includes S-adenosylmethionine decarboxylases from eukaryotes.

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.
Enolpyruvate transferase domain (Enolpyruvate_Tfrase_dom)
Type: Domain

This entry represents the core domain of 3-phosphoshikimate 1-carboxyvinyltransferase and UDP-N-acetylglucosamine 1-carboxyvinyltransferase. These proteins transfer enolpryruvate from phosphoenolpyruvate to 3-phosphoshikimate and UDP-N-acetyl-alpha-D-glucosamine respectively .

The domain can also be found in the fungal Pentafunctional AROM polypeptide (also known as 3-dehydroquinate synthase), although is this case it does not cover the whole protein but appears in association with other domains such as

. This protein catalyses 5 consecutive enzymatic reactions in prechorismate polyaromatic amino acid biosynthesis .
Caulimovirus coat protein (Caulimo_coat)
Type: Family

Caulimoviruses are encapsidated plant viruses that contain circular double-stranded DNA . Members of the group include Cauliflower mosaic virus , Carnation etched ring virus (CERV) , Figwort mosaic virus and Soybean chlorotic mottle virus . The viral coat proteins are quite similar, containing a fairly hydrophilic N-terminal region and a highly-basic C-terminal domain, which may be involved in DNA-binding. The sequences contain the motif CxxCxxxHxxxC, which is similarly found in the nucleic acid binding protein of retroviruses .
Radical-activating enzyme, conserved site (Radical_activat_CS)
Type: Conserved_site

In Escherichia coli and related bacteria, the pflA protein (or act) is involved (

) in the activation of pyruvate formate-lyase (gene pflB) under anaerobic conditions by generation of an organic free radical, using S-adenosylmethionine and reduced flavodoxin as cosubstrates to produce 5'-deoxy-adenosine. The activity of pflA is iron-dependent. A protein highly similar to pflA and termed pflC is probably involved in the activation of a second pyruvate format lyase (gene pflD). The pflA/pflC proteins belong to a family that also includes Bacteriophage T4 and E. coli nrdG which are involved in the generation of the free radical for the anaerobic ribonucleoside-triphosphate reductase (gene nrdD or sunY). It also includes E. coli hypothetical protein yjjW, Haemophilus influenzae hypothetical protein HI0520 and Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical protein MJ0021. All these proteins possess, in their N-terminal section, a highly conserved region which contains three clustered cysteines which are involved in iron-binding.