SII-SWORD/CoKE huggingface dataset:
Uroporphiryn-III C-methyltransferase, conserved site (Uropor_MeTrfase_CS)
Type: Conserved_site

Uroporphyrin-III C-methyltransferase (

)(SUMT) catalyses the transfer of two methyl groups from S-adenosyl-L-methionine to the C-2 and C-7 atoms of uroporphyrinogen III to yield precorrin-2 via the intermediate formation of precorrin-1. SUMT is the first enzyme specific to the cobalamin pathway and precorrin-2 is a common intermediate in the biosynthesis of corrinoids such as vitamin B12, siroheme and coenzyme F430.

The sequences of SUMT from a variety of eubacterial and archaebacterial species are currently available. In species such as Bacillus megaterium (gene cobA), Pseudomonas denitrificans (cobA) or Methanobacterium ivanovii (gene corA) SUMT is a protein of about 25 to 30 Kd. In Escherichia coli and related bacteria, the cysG protein, which is involved in the biosynthesis of siroheme, is a multifunctional protein composed of a N-terminal domain, probably involved in transforming precorrin-2 into siroheme, and a C-terminal domain which has SUMT activity.

The sequence of SUMT is related to that of a number of P. denitrificans and Salmonella typhimurium enzymes involved in the biosynthesis of cobalamin which also seem to be SAM-dependent methyltransferases . The similarity is especially strong with two of these enzymes: cobI/cbiL which encodes S-adenosyl-L-methionine--precorrin-2 methyltransferase and cobM/cbiF whose exact
function is not known.
P2X1 purinoceptor (P2X1_purnocptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

Expression of P2X1 receptors produces receptors that are equally well activated by alphabetamethyleneATP and ATP. The properties of the currents so generated are quite comparable to those determined for native P2X receptors, such as those found to be present in smooth muscle .
P2X2 purinoceptor (P2X2_purnocptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

P2X2 receptors (which have been found to be alternatively spliced), are half-maximally activated by a concentration of ATP of ~10 micromolar. In contrast, alphabetamethyleneATP is found to be largely ineffective. This agonist profile has been found to be shared by the P2X4, P2X5 and P2X6 receptors. The single-channel properties of the P2X2 receptor are quite similar to those noted for the native receptor present on PC12 cells .
P2X3 purinoceptor (P2X3_purnocptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

When expressed, P2X3 receptors (like P2X1 receptors) are found to be equally well activated by alphabetamethyleneATP and ATP. P2X3 receptors desensitise rapidly, with the decay being best-fit by two exponentials, with time constants of ~50 and 300 ms .
P2X4 purinoceptor (P2X4_purnocptor)
Type: Family

The P2X4 receptor (along with P2X2, P2X5 and P2X6) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. There is some evidence that P2X4 may heteropolymerise with P2X6, since they are often found together in native tissues, and can be co-immunoprecipitated. Splice variants of the P2X4 receptor have been detected .

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.
P2X5 purinoceptor (P2X5_purnocptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

The P2X5 receptor (along with P2X2, P2X4 and P2X6) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. Splice variants of P2X5 have been detected .
P2X6 purinoceptor (P2X6_purnocptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

The P2X6 receptor (along with P2X2, P2X4 and P2X5) falls into a group of receptors that are sensitive to ATP, but not alphabetamethyleneATP. There is some evidence that P2X6 may heteropolymerise with P2X4, since they are often found together in native tissues, and can be co-immunoprecipitated. P2X6 and P2X4 receptors are present in the gastrointestinal tract, being involved in synaptic transmission, taste sensation, and pain, among other functions. P2XR6 is present in capillary vessels in the proximal region of the gut and to a lesser extent in the distal region .
P2X7 purinoceptor (P2X7_purinoceptor)
Type: Family

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

This entry represents P2X7 (also known as P2Z receptor), which, when P2X7 receptor is expressed, it is found to have different functional properties from those of P2X1-P2X6. Key properties of the current produced are little rectification or desensitisation, and strong potentiation of responses when the concentration of extracellular Ca2+ and/or Mg2+ are reduced. It is also found to be relatively insensitive to ATP. In certain studies, prolonged activation of expressed P2X7 receptors causes cell permeabilization, and lysis.
Keratin, type II (Keratin_II)
Type: Family

Intermediate filaments (IF) are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide.

Type II keratins are the basic or neutral courterparts to the acidic type I keratins. Each type II keratin forms a heterodimer with a specific acidic keratin, and the heterodimers are organised into tetramers and then into chains . Type II keratins consist of head-, rod- and tail-like structures, the rod being constructed from three linked coils: 1A, 1B and 2. The head and tail structures of the type 2 keratins are highly variable low-complexity regions.

This protein family also includes Intermediate filament protein ON3 from Carassius auratus (Goldfish), one of the non-neuronal predominant intermediate filament proteins of the visual pathway .
Nucleoside-specific channel-forming protein Tsx (Channel_Tsx)
Type: Family

The tsx gene of Escherichia coli encodes an outer membrane protein, Tsx, which constitutes the receptor for colicin K and Bacteriophage T6, and functions as a substrate-specific channel for nucleosides and deoxy- nucleosides . The protein contains 294 amino acids, the first 22 of which are characteristic of a bacterial signal sequence peptide. The putative mature form of Tsx contains 272 residues with a calculated Mr of 31418. The Tsx sequence shows an even distribution of charged residues and lacks extensive hydrophobic stretches . Tsx shows no significant similarities to the channel-forming proteins OmpC, OmpF, PhoE and LamB from the E. coli outer membrane.
Invertebrate colouration protein (Invtbrt_color)
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. 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.

A number of lipocalins act in invertebrate colouration and are represented in this entry. These include: bilin binding protein from the cabbage white butterfly (Pieris brassicae), the closely related protein insecticyanin from Manduca sexta (Tobacco hawkmoth) and the lobster protein crustacyanin. Like other members of the family, they bind small molecules, and gain their colourant properties from interaction with their ligands.
Colicin lysis protein (Lysis_col)
Type: Family

The DNA sequence of the entire colicin E2 operon has been determined . The operon comprises the colicin activity gene (ceaB), the colicin immunity gene (ceiB) and the lysis gene (celB), which is essential for colicin release from producing cells . A putative LexA binding site is located upstream from ceaB, and a rho-independent terminator structure is located downstream from celB . Comparison of the amino acid sequences of colicin E2 and cloacin DF13 reveal extensive similarity. These colicins have different modes of action and recognise different cell surface receptors; the two major regions of heterology at the C terminus, and in the C-terminal end of the central region are thought to correspond to the catalytic and receptor-recognition domains, respectively .
Pyocin S killer protein (Pyocin_killer)
Type: Family

Pyocins are polypeptide toxins produced by, and active against, bacteria. S-type pyocins cause cell death by DNA breakdown due to endonuclease activity . Pyocins S1 and S2 are S-type bacteriocins of Pseudomonas aeruginosa with different receptor recognition specificities . The genetic determinants of these pyocins have been cloned from the NIH-H and PAO chromosomes of P. aeruginosa. The determinants each constitute an operon that encodes two proteins of molecular weight 65,600 and 10,000 (pyocin S1) or 74,000 and 10,000 (pyocin S2) with a characteristic sequence (P box), a possible regulatory element involved in the induction of pyocin production, in the 5' upstream region . These pyocins have almost identical sequences, except in the N-terminal portions of the large proteins, which are substantially different. This similarity suggests that S1 and S2 pyocins, like pyocin AP41, originated from a common ancestor of the E2 group colicins. Purified pyocins S1 and S2 constitute a complex of the two proteins. Both pyocins cause breakdown of chromosomal DNA and complete inhibition of lipid synthesis in sensitive cells. The large protein (not the complex), shows
in vitro
DNase activity. This activity is inhibited by the small protein of either pyocin .
Colicin E1 (microcin) immunity protein (Microcin)
Type: Family

The structural and functional relationships among independently cloned segments of the plasmid ColE1 region that regulates and codes for colicin E1 (cea), immunity (imm) and the mitomycin C-induced lethality function (lys) have been analysed . A model for the structure and expression of the colicin E1 operon has been proposed in which the cea and lys genes are expressed from a single inducible promoter that is controlled by the lexA repressor in response to the SOS system of Escherichia coli . The imm gene lies between the cea and lys genes and is expressed by transcription in the opposite direction from a promoter located within the lys gene . This arrangement indicates that the transcriptional units for all three genes overlap. It is proposed that the formation of anti-sense RNA may be an important element in the coordinate regulation of gene expression in this system .