SII-SWORD/CoKE huggingface dataset:
Cytochrome c-type biogenesis protein CcmB (Cyt_c_biogenesis_CcmB)
Type: Family

This entry represents cytochrome c-type biogenesis protein CcmB (HelB) from bacteria and plants.

CcmB is the product of one of a cluster of ccm genes that are necessary for cytochrome c biosynthesis in bacteria and is required for the export of haem to the periplasm . Plant mitochondria have kept a cytochrome c biogenesis pathway inherited from their prokaryote ancestor and also have a CcmB homologue, but in plants the ccm genes are distributed between the nuclear and the mitochondrial genomes instead of being coded in a single operon .
Type III secreted modular tyrosine phosphatase, SptP/YopH (Tyr_Pase_SptP/YopH)
Type: Family

Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior . There have been four secretion systems described in animal enteropathogens, such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia .

The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis . However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself, type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.

Exotoxins secreted by the type III system do not possess a secretion signal, and are considered unique for this reason . Salmonella/Yersinia spp. secrete a protein, SptP, with tyrosine phosphatase activity . SptP exerts its function by acting as a GTPase-activating protein, and counteracts the effects of SopE . This is similar to the Yersinia exotoxin YopH, which degrades host cell signal transduction .

X-ray crystal structures of the Yersinia tyrosine phosphatase (PTPase) in complex with tungstate and nitrate have been solved to 2.4A resolution . The fold belongs to the α-β class. The crystal structure reveals that the nucleophilic cysteine (Cys 403) is positioned at the centre of a distinctive phosphate-binding loop. This loop is at the hub of several hydrogen-bond arrays that not only stabilise a bound oxyanion, but may activate Cys 403 as a reactive thiolate. Binding of tungstate triggers a conformational change that traps the oxyanion and swings Asp 356, an important catalytic residue that resides in a flexible loop, by ~6A into the active site .
Claudin-1 (Claudin1)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-1 was the first member of the claudin family to be identified as a tight junction component . The human isoform of claudin-1 was originally termed senescence-associated epithelial membrane protein 1 (SEMP1) , but has since been reclassified.
Claudin-3 (Claudin3)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-3 was originally termed rat ventral prostate 1 protein (RVP1), and Clostridium perfringens enterotoxin receptor 2 (CPETR2). It was reclassified as claudin-3 on the basis of cDNA similarity with claudins-1 and -2, and antibody studies that showed it to be expressed at tight junctions .
Claudin-4 (Claudin4)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-4 was originally termed Clostridium perfringens enterotoxin receptor (CPE-R). It was reclassified as claudin-4 on the basis of cDNA sequence similarity with claudins-1 and -2, and antibody studies that showed it to be expressed at tight junctions .
Claudin-5 (Claudin5)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-5 was originally termed lung-specific membrane protein, brain endothelial cell clone 1 protein (BEC1), and transmembrane protein deleted in velo-cardio-facial syndrome (TMVCF). It was reclassified as claudin-5 on the basis of cDNA sequence similarity with claudins-1 and -2, and antibody studies that showed it to be expressed at tight junctions . Claudin-5 may play an important role in development, since the gene is frequently deleted in velo-cardio-facial/DiGeorge syndrome patients .
Claudin-7 (Claudin7)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-7 was identified through searching expressed sequence tag (EST) databases for sequences similar to claudin-1 and -2. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions .
Claudin-9 (Claudin9)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-9 was identified through cDNA database searching, pursuing sequences similar to other claudin family members . Human and mouse isoforms have been cloned. Claudin-9 shares ~25-70% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-6.
Claudin-10 (Claudin10)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-10 was identified through cDNA database searching, pursuing sequences similar to other claudin family members . Human and mouse isoforms have been cloned. Claudin-10 shares ~20-45% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-15.
Claudin-11 (Claudin11)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .

Claudin-11 was originally termed oligodendrocyte-specific protein (OSP). It was reclassified as claudin-11 due to its sequence similarity to claudins and its ability to form TJ strands in transfected fibroblasts. Claudin-11 expression is highly regulated during development and it has been postulated that it may play an important role in the growth and differentiation of oligodendrocytes and other cells outside the CNS .
Cytochrome c-type biogenesis protein CcmC (Cyt_c_biogenesis_CcmC)
Type: Family

Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK , CcmF , NrfE and CcbS . These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.

The gene products of the hel and ccl loci have been shown to be required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus . Genetic and molecular analyses show that the hel locus contains at least 4 genes, helA, helB, helC and orf52. HelA is similar to the ABC transporters and helA, helB, and helC are proposed to encode an export complex . It is believed that the hel-encoded proteins are required for the export of haem to the periplasm, where it is subsequently ligated to the c-type apocytochromes . However, while CcmB and CcmC have the potential to interact with CcmA, the 3 gene products probably associating to form a complex with (CcmA)2-CcmB-CcmC stoichiometry, the substrate for the putative CcmABC-transporter is probably neither haem nor c-type apocytochromes . Hydropathy analysis suggests the presence of 6 TM domains.
2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase (DHB_DH)
Type: Family

The absence of free iron molecules in the surrounding environment triggers transcription of gene clusters that encode both siderophore-synthesis enzymes, and receptors that recognise iron-bound siderophores . Classic examples are the enterobactin/enterochelin clusters found in Escherichia coli and Salmonella, although similar moieties in other pathogens have been identified. The enzymic machinery that produces vibrionectin in Vibrio cholerae is such a homologue .

EntA, a 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase enzyme, is the third enzyme in the biosynthesis of 2,3-dihydroxybenzoic acid (DHB) from chorismate in Escherichia coli. It converts isochorismate to DHB, used for the synthesis of iron chelator enterobactin. Bacillus subtilis possesses similar genes involved in siderophore biosynthesis . Deletion studies involving EntA-mutants have shown that it is essential for virulence .
Mutator MutT (Mutator_MutT)
Type: Family

MutT is a small bacterial protein (~12-15kDa) involved in the GO system . MutT is known as a mutator gene because mutations in the gene specifically increase the rate of AT:GC tranversions. MutT is a 7,8-dihydro-8-oxoguanine triphosphatase converting 8-oxoguanine triphosphatase to the monophosphate with high efficiency. It acts both on 8-oxoGTP as well as 8-oxodGTP. It also can convert, less efficiently, the GDP and dGDP forms to the monophosphates . Consequently it reduces the availability of 8-oxoGTP and the rate of mutation. It was suggested that MutT may ensure transcriptional fidelity, removing 8-oxo-GTP from the ribonucleotide triphosphate pool, however, due to the lower efficiency of RNA polymerase 8-oxo-GTP incorporation, MutT is probably not a major contributor to transcriptional fidelity [

.

A short conserved N-terminal region of mutT (designated the MutT domain) is also found in a variety of other prokaryotic, viral, and eukaryotic proteins . Recently, the generic name `NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moiety X) has been coined for this domain family .

The solution structure of the MutT enzyme has been solved by NMR . The structure is globular and compact, and contains a five-stranded mixed β-sheet. The parallel portion of the sheet is sandwiched between two α-helices, forming an α+β fold.
Mutator MutX protein (Mutator_MutX_prot)
Type: Family

Like MutT (

), MutX protein hydrolyses all canonical nucleoside triphosphates at different rates, with a preference for dGTP, yielding nucleoside monophosphates and inorganic pyrophosphate . Despite the similarity in enzymatic activity, the two proteins have distinct primary and quaternary structures. Their sequences share only a small region of similarity (the MutT domain), and under the same conditions in which MutT exists as a monomer in solution, MutX behaves as a trimer .
Oxidized purine nucleoside triphosphate (8ODP)
Type: Family

This entry represents Oxidized purine nucleoside triphosphate hydrolase (8ODP, also known as 7,8-dihydro-8-oxoguanine triphosphatase and MHT1), and similar Nudix hydrolase domain-containing proteins from bacteria, eukaryots and archaea. This protein has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP and catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA . It was originally considered to play an important role as sanitizer of the oxidized nucleotide pool . However, later studies indicate that NUDT1 plays a redundant role in eliminating oxidized nucleotides and that it is not essential for cancer cell proliferation and survival .
Dihydroneopterin triphosphate diphosphatase (DHNTPase)
Type: Family

Dihydroneopterin triphosphate diphosphatase is a Nudix domain containing enzyme involved in folate biosynthesis. It catalyses the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. It can also hydrolyse nucleoside triphosphates with a preference for dATP .
Bis(5'-nucleosyl)-tetraphosphatase (Tetra_PHTase)
Type: Family

Bis(5'-nucleosyl)-tetraphosphatase, also known as diadenosine tetraphosphate (Ap4A) hydrolase, is a member of the Nudix hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms . Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria . Besides the signature nudix motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the nudix superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies .
Cytochrome c-type biogenesis protein (Cyt_c_biogenesis)
Type: Family

Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK , CcmF , NrfE and CcbS . These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.
Cytochrome c-type biogenesis protein CcmF (Cyt_c_biogenesis_CcmF)
Type: Family

Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK , CcmF , NrfE and CcbS . These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.

The gene products of the hel and ccl loci have been shown to be required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus. The ccl locus contains two genes, ccl1 and ccl2, each of which possesses typical signal sequences to direct them to the periplasm . Ccl1 is similar to proteins encoded by chloroplast and mitochondrial genes, suggesting analogous functions in these organelles. It is believed that the hel-encoded proteins are required for the export of haem to the periplasm, where it is subsequently ligated to the c-type apocytochromes .

The CycK and CycL proteins of Bradyrhizobium japonicum share up to 53% amino acid sequence identity with R. capsulatus proteins Cc11 and Cc12 proteins, respectively. CycK and CycL proteins, which are encoded by the cycHJKL-cluster, may form part of a cytochrome c-haem lyase complex whose active site faces the periplasm .
Probable cytochrome c biosynthesis protein, plants (Cyt_c_biogenesis_plant)
Type: Family

Analysis of a transcribed region in the mitochondrial genome from members of the genus Oenothera, revealed an open reading frame (ORF) that is also conserved in Daucus carota (Carrot) . Extensive RNA editing (46 C to U transitions) alters the
Oenothera bertiana mRNA sequence, yielding a sequence with high similarity to the homologous gene product in Marchantia polymorpha (Liverwort). The deduced polypeptides share significant similarity with the ccl1-encoded protein involved in cytochrome c biogenesis in the photosynthetic bacterium Rhodobacter capsulatus. A highly conserved domain is also found in plastid ORFs, suggesting that these bacterial, chloroplast and mitochondrial genes encode polypeptides with analogous functions in assembly and maturation of cytochromes c .
Cytochrome c-type biogenesis protein NrfE (Cyt_c_biogenesis_NrfE)
Type: Family

Within mitochondria and bacteria, a family of related proteins is involved in the assembly of periplasmic c-type cytochromes: these include CycK , CcmF , NrfE and CcbS . These proteins may play a role in guidance of apocytochromes and haem groups for their covalent linkage by the cytochrome-c-haem lyase. Members of the family are probably integral membrane proteins, with up to 16 predicted transmembrane (TM) helices.

A seven-gene operon, designated nrf, has been shown to be essential for formate-dependent nitrite reduction to ammonia by enteric bacteria . Expression of lac fused to nrfA, nrfE or nrfG is regulated by oxygen repression, FNR-dependent anaerobic induction, nitrite induction and nitrate repression during anaerobic growth. NrfE is a hydrophobic, integral membrane protein that shares a high degree of similarity with the CdI1 protein of Rhodobacter capsulatus implicated in the assembly of periplasmic c-type cytochromes . Hydropathy analysis reveals up to 16 putative TM domains.
Snake three-finger toxin (Snake_3FTx)
Type: Family

Three finger toxins (3FTx) constitute an important superfamily of snake venom proteins. All have three β-stranded loops resembling three fingers, emerging from a globular core and stabilised by four conserved disulfide bridges. They are diverse in their biological functions, and include neurotoxins, cardiotoxins, cytotoxins, fasciculins, platelet-aggregation inhibitors and specific ion-channel blockers .

Neurotoxins interfere with cholinergic transmission at postsynaptic sites in the peripheral and central nervous systems and consist of alpha-neurotoxins, kappa-neurotoxins and muscarinic toxins. Cardiotoxins are the second largest group and are only found in cobra venoms . Acetylcholine receptors are blocked by alpha-neurotoxin and cardiotoxins (cytotoxins) . Some members of this family also inhibit GABAA receptors (GABAARs) with different efficacy . Fasciculins (cytotoxins) inhibit L-type calcium-channel blockers .
Snake cytotoxin, cobra-type (Cytotoxin_Cobra)
Type: Family

Snake toxins belong to a family of proteins which groups short and long neurotoxins, cytotoxins and short toxins, as well as a other miscellanous venom peptides. Cytotoxins (CTs) are small (~60 amino acids) proteins, which are abundant in the venom of the snakes of the Elapidae family . The cytotoxic properties of CTs are mediated by their interaction with the cell membrane . Mu-elapitoxin-Na1a is a highly selective and potent inhibitor of inhibitor of the hNav1.8/SCN10A channel and acts reversibly. In rodent models it has a potent analgesic effect and displayed no evident cytotoxicity and cardiotoxicity or obvious adverse responses being a promising analgesic to manage pain .

This family consists mainly of cytotoxins from the Naja genus of snakes (cobras).
Interleukin-6-like (IL-6-like)
Type: Family

This entry represents interleukin-6 (IL6), also refered to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, it is a cytokine involved in a wide variety of biological functions . It plays an essential role in the final differentiation of B-cells into IG-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation and, in hepatocytes, acute phase reactants .

This entry also includes the interleukin-6 homologue from human herpesvirus 8 type P which binds to interleukin-6 receptor subunit beta IL6ST and initiates a signal transduction. It is able to induce blood to lymphatic endothelial cell differentiation and, in infected primary effusion lymphoma cells, it promotes cell proliferation, protects them from apoptosis, and promotes immune evasion of interferon activity .