Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all
of which can be fatal to patients who are immunocompromised []. Viral infection commences with recognition of host cell receptors by means of specialised proteins on viral surfaces. The adenovirus
fibre protein `knob domain' at the C terminus is one such receptor-binding protein subunit. The crystal structure of the knob domain reveals a trimeric organisation, each subdomain folded into 2 functionally
distinct β-sheets. The V sheet is highly conserved, and provides contact surfaces in the formation of the trimer, while the R sheet is more variable, and may play a role in viral-receptor interactions. The
overall shape of the trimer resembles a 3-bladed propeller, with a central surface depression and 3 valleys formed by the symmetry-related R sheets. Sequence comparison of different types of adenovirus fibre protein
suggests an overall similarity in the structure of the knob domain. The main conserved regions lie in the central surface depression around the 3-fold symmetry axis [
]. The N terminus of the proteincontains the 'shaft' region.
The capsid proteins of plant icosahedral positive strand RNA viruses form 4 different domains, a positively charged, N-terminal 'R' domain, which interacts with RNA (66 residues); a connecting arm, 'a' (35 residues); a central, surface 'S' domain, which forms the virion shell; and a projecting, C-terminal `P' domain [
]. Some of the viruses lack either the R or P domains. The S domain contains from 158 to 166 amino acids and comprises 8 anti-parallel β-strands, which form a twisted sheet or jelly-roll fold. This structure is shared by a number of plant viral capsid proteins, which include: Carmovirus, Dianthovirus, Sobemovirus, Tombusvirus and an unidentified tobacco necrosis virus [].
Adenoviruses are responsible for diseases such as pneumonia, cystitis, conjunctivitis and diarrhoea, all
of which can be fatal to patients who are immunocompromised []. Viral infection commences with recognition of host cell receptors by means of specialised proteins on viral surfaces. Specific attachment
of adenovirus is achieved through interactions between host-cell receptors and the adenovirus fibre protein and is mediated by the globular carboxy-terminal domain of the adenovirus fibre protein, rather than the
'shaft' region represented by this family. The alignment of this family contains two copies of a fifteenresidue repeat found in the 'shaft' region of adenoviral fibre proteins.
The nebulin-like motif or nebulin repeat is a tandemly repeated actin-binding module of about 35 amino acids. The repeat is named after the nebulin protein, which is a large protein specific for vertebrate skeletal muscle that may regulate the length of thin filaments. Nebulin contains about 185 copies of the repeat and those in the central part of nebulin are organised into seven-module super-repeats, which seems to reflect an interaction with tropomysin/troponin [
]. Nebulin repeats occur in metazoan actin-binding proteins, most of which are specific for muscle tissues. Most nebulin repeat proteins contain a C-terminal SH3 domain and/or a N-terminal LIM zinc-binding domain. The repeats in nebulin and nebulette bind filamentous actin (F-actin) and may also associate with tropomyosin and troponin. The nebulin repeat has a predicted α-helical secondary structure and contains a central conserved SXXXY motif [,
,
].
The ZU5 domain is a domain of 90-110 residues present in zona occludens 1 (ZO-1) protein, in unc5-like netrin receptors and in ankyrins. The ZU5 domain is named after the mouse tight junction protein ZO-1 and the C. elegans uncoordinated protein 5 (unc-5) and related Unc5-like netrin receptors. ZU5 domains are found in eukaryotic proteins that in most cases contain a C-terminal death domain. Other domains which can be found N-terminal to a ZU5 domain are ankyrin repeats; Ig-like and TSP1 repeats; PDZ, SH3 and guanylate kinase; or leucine-rich repeats (LRR) [
,
,
,
]. The ZU5 domain can function as a spectrin-binding domain in ankyrins [], and participates in induction of apoptosis and binding of melanoma-associated antigen D1 (MAGE-D1/NRAGE) in UNC5H1-3 [].
Lipoxygenases ([intenz:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes []. Sequence data is available for the following lipoxygenases: Plant lipoxygenases (
). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [
].Mammalian arachidonate 5-lipoxygenase (
).
Mammalian arachidonate 12-lipoxygenase (
).
Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;
).
The iron atom in lipoxygenases is bound by four ligands, three of which are
histidine residues []. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [] to be important for the activity of lipoxygenases.This entry represents mammalian lipoxygenases.
The Herpesvirus major capsid protein (MCP) is the principal protein of the icosahedral capsid, forming the main component of the hexavalent and probably the pentavalent capsomeres. The capsid shell consists of 150 MCP hexamers and 12 MCP pentamers. One pentamer is found at each of the 12 apices of the icosahedral shell, and the hexamers form the edges and 20 faces [
]. The MCP can be considered as having three domains: floor, middle and upper. The floor domains form a thin largely continuous layer, or shell, and are the only parts that interact directly to form intercapsomeric connections. They also interact with the internal scaffolding protein during capsid assembly []. The remainder of the protein extends radially outward from the capsid producing the hexamer and pentamer capsomere structures. The middle domains are involved in binding to the triplexes that lie between and link adjacent capsomeres []. The upper domains form the tops of the hexamer and pentamer towers and are the binding sites for the small capsid protein VP26 in the hexons and for tegument proteins in the pentons.
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 [
,
,
].Neuropeptide receptors are present in very small quantities in the cell
and are embedded tightly in the plasma membrane. The neuropeptides exhibita high degree of functional diversity through both regulation of peptide
production and through peptide-receptor interaction []. The mammaliantachykinin system consists of 3 distinct peptides: substance P, substance
K and neuromedin K. All possess a common spectrum of biological activities,including sensory transmission in the nervous system and contraction/
relaxation of peripheral smooth muscles, and each interacts with aspecific receptor type.
In the periphery, NK2 receptors are found in smooth muscle of the
respiratory, gastrointestinal and urogenital systems. NK2 receptorsactivate the phosphoinositide pathway through a pertussis-toxin-insensitive
G-protein, probably of the Gq/G11 class.
Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [,
,
].On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [
] into eight families or clusters, which generally correlate with the nature of the solute bound. This entry represents a domain found in the solute-binding protein family 5. Family 5 members include:Periplasmic oligopeptide-binding proteins (oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (oppA, amiA or appA)Periplasmic dipeptide-binding proteins of Escherichia coli (dppA) and Bacillus subtilis (dppE)Periplasmic murein peptide-binding protein of E. coli (mppA) Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzaePeriplasmic nickel-binding protein (nikA) of E. coliHaem-binding lipoprotein (hbpA or dppA) from H. influenzaeLipoprotein xP55 from Streptomyces lividansHypothetical proteins from H. influenzae (HI0213) and Rhizobium sp. (strain NGR234) symbiotic plasmid (y4tO and y4wM)HTH-type transcriptional regulator SgrR from E. coli. The solute-binding domain is localised in its C-terminal [
].
Phagocytes form the first line of defence against invasion by microorganisms. Engulfing of bacteria by
neutrophils is accompanied by the consumption of large amounts of oxygen, a so-called respiratory burst.Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous
disease (CGD), in which patients are predisposed to infection, often from otherwise non-pathogenic bacteria. Regulation of the respiratory burst takes place at the phagocytic vacuole. The process is mediated by NADPH
oxidase, which transports electrons across the plasma membrane to form superoxide (an oxygen molecule with an extra electron that is toxic to normal cells) in the vacuole interior. The electrons are carried across
the membrane by a short electron transport chain in the form of an unusual flavocytochrome B [].To conserve NADPH and avoid the toxic effects of superoxide, the oxidase remains inactive until it receives
an appropriate stimulus. Activation involves the participation of a number of cytosolic proteins, some of which attach to the flavocytochrome. P47phox, p67phox and p40phox are specialised components of phagocytic
cells. All contain SH3 domains, by means of which they attach to proline-rich regions of other proteins. Upon activation, p40phox translocates to the region of the plasma membrane forming the phagocytic vacuole,
where, with phosphorylated p47phox and p67phox, it associates with hydrophilic regions of the flavocytochrome
This domain is found at the N terminus of a subset of sigma54-dependent transcriptional activators in several proteobacteria, including activators of phenol degradation such as XylR. It is found adjacent to
.
This entry represents group a small conserved region found in 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta, also known as phospholipase C beta (PLC-beta) [
].
Signal transduction response regulator, propionate catabolism activator, N-terminal
Type:
Domain
Description:
Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions [
]. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk []. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more []. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) []. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [
,
].This entry represents a domain found at the N terminus of several sigma54- dependent transcriptional activators including PrpR, which activates catabolism of propionate. In Salmonella enterica subsp. enterica serovar Typhimurium, PrpR acts as a sensor of 2-methylcitrate (2-MC), an intermediate of the 2-methylcitric acid cycle used by this bacterium to convert propionate to pyruvate [
].
This entry contains proteins from Fijiviruses including P7-1 protein from Southern rice black-streaked dwarf virus (SRBSDV) and the probable non-structural 41.0 kDa protein from Maize rough dwarf virus (MRDV). P7-1 induces the formation of virus-containing tubules in infected plant and insect vector cells allowing its efficient transmission especially in high temperatures [
,
].
This family consists of several PV-1 (PLVAP) proteins, which seem to be specific to vertebrates. PV-1 is a component of the endothelial fenestral and stomatal diaphragms [
,
]. PV-1 is retained on the cell surface of enddotelial cells by structures capable of forming diaphragms, but undergoes rapid internalization and degradation in the absence of these structures [].
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. In PSII, the oxygen-evolving complex (OEC) is responsible for catalysing the splitting of water to O(2) and 4H+. The OEC is composed of a cluster of manganese, calcium and chloride ions bound to extrinsic proteins. In cyanobacteria there are five extrinsic proteins in OEC (PsbO, PsbP-like, PsbQ-like, PsbU and PsbV), while in plants there are only three (PsbO, PsbP and PsbQ), PsbU and PsbV having been lost during the evolution of green plants [
].This family represents the PSII extrinsic protein PsbU, which forms part of the OEC in cyanobacteria and red algae. PsbU acts to stabilise the oxygen-evolving machinery of PSII against heat-induced inactivation, which is crucial for cellular thermo-tolerance [
].
VANGL proteins play important roles in the establishment of planar cell polarity (PCP) [
]. Vangl2 is required for retinal axon guidance [], kidney-branching morphogenesis and glomerular maturation []. It also plays a role in the orientation of stereociliary bundles in the cochlea and is required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process []. It is required for cell surface localization of FZD3 and FZD6 in the inner ear [].
Members of this entry contain a region found exclusively in eukaryotic sodium channels or their subunits, many of which are voltage-gated. Members very often also contain between one and four copies of
and, less often, one copy of
.
This histidine kinase protein is paired with an adjacent response regulator (
) gene. It co-occurs with a variant sortase enzyme (
), usually in the same gene neighbourhood, in proteobacterial species most of which are marine, and with an LPXTG motif-containing sortase target conserved protein (
). Sortases and LPXTG proteins are far more common in Gram-positive bacteria, where sortase systems mediate attachment to the cell wall or cross-linking of pilin structures. We give this predicted sensor histidine kinase the gene symbol psdS, for Proteobacterial Dedicated Sortase system Sensor histidine kinase.
This entry includes FAM107A/B. FAM107A (also known as DRR1) is an actin-associated protein that plays important roles in tumor cell growth, neuron survival and spine formation [
]. The function of FAM107B is not clear.
Proteobacterial sortase system peptidoglycan-associated protein
Type:
Family
Description:
A newly defined histidine kinase (
) and response regulator (
) gene pair occurs exclusively in Proteobacteria, mostly of marine origin, nearly all of which contain a subfamily 6 sortase (
) and its single dedicated target protein (
) adjacent to to the sortase. This protein family shows up in only in those species with the histidine kinase/response regulator gene pair, and often adjacent to that pair. It belongs to the OmpA protein family (
). Its function is unknown. We assign the gene symbol pdsO, for Proteobacterial Dedicated Sortase system OmpA family protein.
NHPM bacteriocin system ABC transporter, peptidase/ATP-binding protein
Type:
Family
Description:
This protein describes an multidomain ABC transporter subunit that is one of three protein families associated with some regularity with a distinctive family of putative bacteriocins. It includes a bacteriocin-processing peptidase domain at the N terminus. Model describes a conserved propeptide region for this bacteriocin family, unusual because it shows obvious homology a region of the enzyme nitrile hydratase up to the classic Gly-Gly cleavage motif. This family is therefore predicted to be a subunit of a bacteriocin processing and export system characteristic to this system that we designate NHPM, Nitrile Hydratase Propeptide Microcin.
NHPM bacteriocin system ABC transporter, ATP-binding protein
Type:
Family
Description:
Members of this protein family are ABC transporter ATP-binding subunits, part of a three-gene putative bacteriocin transport operon. The other subunits include another ATP-binding subunit (
), which has an N-terminal propeptide cleavage domain, and an HlyD homologue (
). In a number of genomes, a conserved propeptide sequence with a classic Gly-Gly motif
This enzyme, aspartate 4-decarboxylase (
), removes the side-chain carboxylate from L-aspartate, converting it to L-alanine plus carbon dioxide. It is a PLP-dependent enzyme, homologous to aspartate aminotransferase (
).
This enzyme is proposed here to be a form of aspartate 1-decarboxylase, pyridoxal-dependent, that represents a non-orthologous displacement to the more widely distributed pyruvoyl-dependent form (
). Aspartate 1-decarboxylase makes beta-alanine, used usually in pathothenate biosynthesis, by decarboxylation from asparatate. A number of species with the PanB and PanC enzymes, however, lack PanD. This protein family occurs in a number of Proteobacteria that lack PanD. This enzyme family appears to be a pyridoxal-dependent enzyme (see
). The family was identified by Partial Phylogenetic Profiling; members in Geobacter sulfurreducens, Geobacter metallireducens, and Pseudoalteromonas atlantica are clustered with the genes for PanB and PanC. We suggest the gene symbol panP (panthothenate biosynthesis enzyme, Pyridoxal-dependent).
This entry describes a repeat originally found in proteins from two species of Verrucomicrobia (Chthoniobacter flavus and Verrucomicrobium spinosum) and in four different proteins of Gloeobacter violaceus PCC7421. In the Verrucomicrobial species, the repeat region is followed by a PEP-CTE protein-sorting signal, suggesting an extracellular location. Members of this group of proteins are found in different bacterial taxa.
This entry is represented by Bacteriophage 933W, GpQ. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.This family consists of several phage antitermination protein Q and related bacterial sequences. Phage 993W gene Q encodes a phage-specific positive regulator of late gene expression, thought, by analogy to the corresponding gene of phage lambda, to be a transcription antiterminator. GpQ positively regulates expression of the phage late gene operons. Bacterial host RNA polymerase modified by antitermination proteins transcribes through termination sites that otherwise prevent expression of the regulated genes [
,
].
This family consists of several Tenuivirus PVC2 proteins from Rice grassy stunt virus, Maize stripe virus and Rice hoja blanca virus. The function of this family is unknown.
Members of this family are blue-copper redox proteins designated sulfocyanin, mainly from the archaeal genera Sulfolobus [
]. Sulfocyanin is a component of the respiratory supercomplex SoxM [].
This entry includes vertebrate transcription factors, some of which are regulated by IL-3/adenovirus E4 promoter binding protein [
]. Others were found to strongly repress transcription in a DNA-binding-site-dependent manner [].
DHOR is a family of di-haem oxidoredictases. It carries the two characteristic Cys-X-Y-Cys-His haem-binding motifs. The C-terminal high-potential site functions as an electron transfer centre, and the N-terminal low-potential site corresponds to the peroxidatic centre. Its probable function is as a peroxidase [
].
This entry contains of several mammalian and one bird sequence from Gallus gallus (Chicken) and represents the N-terminal region of repulsive guidance molecule (RGM). RGM is a GPI-linked axon guidance molecule of the retinotectal system, and controls cell motility, adhesion, immune cell regulation and systemic iron metabolism [
,
]. RGM is repulsive for a subset of axons, those from the temporal half of the retina. Temporal retinal axons invade the anterior optic tectum in a superficial layer, and encounter RGM expressed in a gradient with increasing concentration along the anterior-posterior axis. Temporal axons are able to receive posterior-dependent information by sensing gradients or concentrations of guidance cues. Thus, RGM is likely to provide positional information for temporal axons invading the optic tectum in the stratum opticum [].
This entry represents the N-terminal domain of the avian adenovirus fibre proteins, which have been linked to variations in virulence [
]. Avian adenoviruses possess penton capsomers that consist of a pentameric base associated with two fibres [].
This family consists of several basal layer antifungal peptide (BAP) sequences specific to Zea mays (Maize). The BAP2 peptide exhibits potent broad-range activity against a range of filamentous fungi, including several plant pathogens [
].
DTM1 is an endoplasmic reticulum (ER) membrane protein present in cereals. It is thought to play important roles in the ER membrane during early tapetum development and also in meiocyte development [
].
Entry
represents the family of all lantibiotics related to gallidermin, including epidermin, mutatin, and nisin. This protein family describes the ATP-binding subunit of a gallidermin/epidermin class lantibiotic protection transporter. It is largely restricted to gallidermin-family lantibiotic biosynthesis and export cassettes, but also occurs in orphan transporter cassettes in species that lack candidate lantibiotic precursor and synthetase genes.
A novel genetic system characterised by six major proteins, included a ParB homologue and a ThiF homologue, is designated PRTRC, or ParB-Related,ThiF-Related Cassette. This family is the PRTRC system ThiF family protein.
Members of this family are assigned by homology to the TraD family of conjugative coupling factor. This particular clade serves as a marker for an extended gene region that occurs occasionally on plasmids, including the toluene catabolism TOL plasmid. More commonly, the gene region is chromosomal, flanked by various markers of conjugative transfer and insertion.
Members of this protein family are the putative conjugative coupling factor, TraD (or TraG), rather distantly related to the well-characterised TraD of the F plasmid. Members are associated with conjugative-transposon-like mobile genetic elements of the class that includes SXT, an antibiotic resistance transfer element in some Vibrio cholerae strains.
The predicted protein-sorting transpeptidase that we call exosortase (see
) has distinct subclasses that associated with different types of exopolysaccharide production loci and/or different taxonomic lineages. We designate this relatively divergent cyanobacterial type to be type 3. We propose the gene symbol xrtC. This type coexists with a
-recognised form in Nostoc sp PCC 7120.
Members of this family are archaeal homologues to bacterial PEP-CTERM-sorting protein exosortase (
) [
]. Members of this family are found in species with an archaeal variant sorting motif, PEF-CTE (). They are found in the thermoacidophilic Aciduliprofundum boonei, the mesophilic psychromethanogens Methanosarcina mazei and Methanococcoides burtonii, and in Ferroglobus placidus DSM 10642.
This entry describes a small collection of probable metallophosphoresterases, related to
. Members of this protein family usually have a Sec-independent TAT (twin-arginine translocation) signal sequence, N-terminal to the region modeled by this HMM. This model and
divide a narrow clade of
-related enzymes.
This entry describes a small collection of probable metallophosphoresterases, related to
but with long inserts separating some of the shared motifs such that the homology is apparent only through multiple sequence alignment. Members of this protein family, in general, have a Sec-independent TAT (twin-arginine translocation) signal sequence, N-terminal to the region modeled by this HMM. Members include YP_056203.1 from Propionibacterium acnes KPA171202.
Members of this family include the predicted ATPase, TraG, encoded by transfer region genes of conjugative transposons of Bacteroides, such as CTnDOT, found on the main chromosome. Members also include TraG homologues residing on plasmids in Bacteroides. The protein family is related to the conjugative transfer system ATPase VirB4.
This protein family is the ATP-binding cassette subunit of binding protein-dependent ABC transporter complex that strictly co-occurs with
. TIGRFAMs model
describes a protein domain that occurs singly or as one of up to three repeats in proteins of a number of Actinobacteria, including Propionibacterium acnes KPA171202. The
domain occurs both in an adjacent gene for the substrate-binding protein and in additional (often nearby) proteins, often with LPXTG-like sortase recognition signals. Homologous ATP-binding subunits outside the scope of this family include manganese transporter MntA in Synechocystis sp PCC 6803 and chelated iron transporter subunits. The function of this transporter complex is unknown.
This family consists of several NOA36 proteins (also known as zinc finger protein 330) which contain 29 highly conserved cysteine residues. In mitosis it associates with centromeres and concentrates at the midbody in cytokinesis [
].
This family consists of several PerB or BfpV proteins found specifically in Escherichia coli. PerB is thought to play a role in regulating the expression of BfpA [
].
This entry represents the family 9 carbohydrate-binding module (CBD9), which exhibit an immunoglobulin-like β-sandwich fold, with an additional β-strand at the N terminus [
].Bacterial extracellular cellulases and hemicellulases are involved in the hydrolysis of the major structural polysaccharides of plant cell walls. These are usually modular enzymes that contain catalytic and non-catalytic domains. The CBD9 domain binds to cellulose, xylan, as well as to a range of soluble di- and mono-saccharides, and is found in cellulose- and xylan-degrading enzymes, such as endo-1,4-beta-xylanase () [
].
This entry represents the C-terminal domain of glucodextranase-like proteins found in various prokaryotic membrane-anchored proteins. It shows homology to the carbohydrate-binding unit of some glycosidases [
].
This family consists of several nuclear disruption (Ndd) proteins from T4-like phages. Early in a Bacteriophage T4 infection, the phage ndd gene causes the rapid destruction of the structure of the Escherichia coli nucleoid. The targets of Ndd action may be the chromosomal sequences that determine the structure of the nucleoid [
].
Hepcidin is a antibacterial and anti-fungal protein expressed in the liver and is also a signalling molecule in iron metabolism. The hepcidin protein is cysteine-rich and forms a distorted β-sheet with an unusual disulphide bond found at the turn of the hairpin [
].
Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that has a broad host range in warm-blooded animals. BDV is an enveloped virus, non-segmented, negative-stranded RNA genome and has an organisation characteristic of a member of Bornaviridae in the order of Mononegavirale. This family consists of several BDV P24 (phosphoprotein 24) proteins. They are essential components of the RNA polymerase transcription and replication complex. P24 is encoded by open reading frame II (ORF-II) and undergoes high rates of mutation in humans. They bind amphoterin-HMGB1, a multifunctional protein, directly may cause deleterious effects in cellular functions by its interference with HMGB1 [
]. Horse and human P24 have no species-specific amino acid residues, suggesting that the two viruses related [,
].Numerous interactions of the immune system with the central nervous system have been described. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course and the treatment response [
]. BDV p24 RNA has been detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients with such conditions []. Some studies find a significant difference in the prevalence of BDV p24 RNA in patients with mood disorders and schizophrenia [], whilst others find no difference between patients and control groups []. Consequently, debate about the role of BDV in psychiatric diseases remains alive.
This is a ~120-amino acid protein-protein interaction module that binds DMAP1 (DNA methyltransferase-associated protein 1), a transcriptional co-repressor. It is found at the N terminus of DNMT1 (DNA methyltransferase 1) [
] and animal disco-interacting protein 2 (DIP-2), a protein that maintains morphology of mature neurons [,
]. This domain is also found in N-acetylglucosamine-1-phosphotransferase subunits alpha/beta (GNPTA) and gamma (GNPTG) from animals, which are members of a complex that catalyses the initial step in the formation of the mannose 6-phopsphate targeting signal on newly synthesized lysosomal acid hydrolases. The DMAP1-binding domain mediates the selective binding GlcNAc-1-phosphotranferase to acid hydrolases [,
].The DMAP1-binding domain is predicted to adopt a long helix-turn-helix structure that is rich in leucine residues [
].
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. The low molecular weight transmembrane protein PsbX found in PSII is associated with the oxygen-evolving complex. Its expression is light-regulated. PsbX appears to be involved in the regulation of the amount of PSII [
], and may be involved in the binding or turnover of quinone molecules at the Qb (PsbA) site [].PsbX can be divided into two subfamilies; this one, which is found only in Prochlorococcus, and a shorter one with a much wider taxonomic distribution. The proteins in this subfamily are currently uncharacterised.
These are B subunits from the type II heat-labile enterotoxin. The B subunits form a pentameric ring, which interacts with one A subunit. Thus, the structural arrangement of type I and type II heat-labile enterotoxins are very similar [
].
The arfaptin homology (AH) domain is a protein domain found in a range of proteins, including arfaptins, protein kinase C-binding protein PICK1 [
] and mammalian 69kDa islet cell autoantigen (ICA69) []. The AH domain of arfaptin has been shown to dimerise and to bind Arf and Rho family GTPases [,
], including ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules.The AH domain consists of three α-helices arranged as an extended antiparallel α-helical bundle. Two arfaptin AH domains associate to form a highly elongated, crescent-shaped dimer [
,
].
Protein Interacting with C Kinase 1 (PICK1) is highly expressed in brain and testes. It plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory [
,
]. PICK1 is also critical in the early stages of spermiogenesis. Mice deficient in PICK1 are infertile and show characteristics of the human disease globozoospermia such as round-headed sperm, reduced sperm count, and severely impaired sperm motility []. PICK1 may also be involved in the neuropathogenesis of schizophrenia [].PICK1 contains an N-terminal PDZ domain and a C-terminal BAR domain [
], also designated as AH (arfaptin homology) domain []. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of PICK1 is necessary for its membrane localization and activation [,
].
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. MYM-type zinc fingers were identified in MYM family proteins [
]. Human protein is involved in a chromosomal translocation and may be responsible for X-linked retardation in XQ13.1 [
]. is also involved in disease. In myeloproliferative disorders it is fused to FGF receptor 1 [
]; in atypical myeloproliferative disorders it is rearranged []. Members of the family generally are involved in development. This Zn-finger domain functions as a transcriptional trans-activator of late vaccinia viral genes, and orthologues are also found in all nucleocytoplasmic large DNA viruses, NCLDV. This domain is also found fused to the C termini of recombinases from certain prokaryotic transposons [].
This family consists of secretion proteins like Yersinia YscK. The function of this protein is unknown but it belongs to an operon involved in the secretion of Yop proteins across bacterial membranes [
].
This entry represents Mad1 and Cdc20-bound-Mad2 binding proteins that are involved in the cell-cycle surveillance mechanism called the spindle checkpoint [
]. This mechanism monitors the proper bipolar attachment of sister chromatids to spindle microtubules and ensures the fidelity of chromosome segregation during mitosis. A key player in mitosis is Mad2, which exhibits an unusual two-state behaviour. A Mad1-Mad2 core complex recruits cytosolic Mad2 to kinetochores through Mad2 dimerisation and converts Mad2 to a conformer amenable to Cdc20 binding. p31comet inactivates the checkpoint by binding to Mad1- or Cdc20-bound Mad2 in such a way as to stop Mad2 activation and to promote the dissociation of the Mad2-Cdc20 complex [].
The prokineticin family includes prokinectin itself and related proteins such as BM8 and the AVIToxins. The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. It has been shown that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock [
].
This entry contains a number of proteins from Drosophila melanogaster and other insects. Their function is unknown. Based on its distant similarity to
and conserved pattern of cysteine residues it is possible that these domains are also lipid binding.
The function of Cilia- and flagella-associated protein 107 (CFAP107 or C1orf158) may be a microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating [
].This entry also includes UPF0686 protein C11orf1 and its homologues, whose function is unknown.
Ribonuclease L (RNase L) is a highly regulated, latent endoribonuclease (thus the 'L' in RNase L) and is widely expressed in most mammalian tissues. It is involved in the mediation of the antiviral and pro-apoptotic activities of the interferon-inducible 2-5A system, which blocks infections by certain types of viruses through cleavage of viral and cellular single-stranded RNA [
,
]. RNase L is unique in that it is composed of three major domains; N terminus regulatory ankyrin repeat domain (ARD), followed by a linker, a protein kinase (PK)-like domain and a C-terminal ribonuclease (RNase) domain. The RNase domain has homology with IRE1, also containing both a kinase and an endoribonuclease, that functions in the unfolded protein response (UPR) []. RNase L has been shown to have an impact on the pathogenesis of prostate cancer; the RNase L gene, RNASEL, has been identified as a strong candidate for the hereditary prostate cancer 1 (HPC1) allele [,
,
]. The broad range of biological functions of RNase offers a possibility for RNase L as a therapeutic target.This entry represents the RNase domain of RNase L.
This family consists of several mammalian FGF binding protein 1. Fibroblast growth factors (FGFs) play important roles during foetal and embryonic development [
]. Fibroblast growth factor-binding protein (FGF-BP) 1 is a secreted protein that can bind fibroblast growth factors (FGFs) 1 and 2 [].
Members of this protein family are small, typically about 80 residues in length, and are highly hydrophobic. The gene is found so far only in a subset of the firmicutes in association with genes of the ATP synthase F1 complex or NADH-quinone oxidoreductase. This family includes YwzB from Bacillus subtilis.
Lytic murein transglycosylase D , lipid attachment domain
Type:
Domain
Description:
This entry represents the MltD lipid attachment domain. It is a short N-terminal domain found in membrane-bound lytic murein transglycosylase D (Mltd).
There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements [
,
], as summarised below:Type I enzymes (
) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (
) activities.
Type II enzymes (
) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.
Type III enzymes (
) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (
).
Type IV enzymes target methylated DNA.Type II restriction endonucleases (
) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin [
]. However, there is still considerable diversity amongst restriction endonucleases [,
]. The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone []. This entry represents the C terminus of bacterial enzymes similar to type II restriction endonucleases BsuBI and PstI (
). The enzymes of the BsuBI restriction/modification (R/M) system recognise the target sequence 5'CTGCAG and are functionally identical with those of the PstI R/M system [
].
COX2 (Cytochrome O ubiquinol OXidase 2) is a major component of the respiratory complex during vegetative growth. It transfers electrons from a quinol to the binuclear centre of the catalytic subunit 1. The function of this region is not known.
NC10 stands for Non-helical region 10 and is taken from
. A mutation in this region in
is associated with an increased risk of prostrate cancer. This domain is cleaved from the precursor and forms endostatin. Endostatin is a key tumour suppressor and has been used highly successfully to treat cancer. It is a potent angiogenesis inhibitor [
].Endostatin is a C-terminal fragment of collagen XV/XVIII, a proteoglycan/collagen found in vessel walls and basement membranes. This domain has a compact globular fold similar to that of C-type lectins. Endostatin XVIII is monomeric and contains a heparin-binding epitope and zinc binding sites [
] while endostatin XV is trimeric and contains neither of these sites. The generation of endostatin or endostatin-like collagen XV/XVIII fragments is catalyzed by proteolytic enzymes within the protease-sensitive hinge region of the C-terminal domain. Endostatin inhibits endothelial cell migration in vitro and appears to be highly effective in murine in vivo studies [,
].
This domain is found at the N terminus of a subset of sigma54-dependent transcriptional activators that are involved in regulation of flagellar motility e.g. FleQ in Pseudomonas aeruginosa. It is clearly related to
, but lacks the conserved aspartate residue that undergoes phosphorylation in the classic two-component system response regulator (
).
Tra is a member of the regulatory pathway controlling female somatic sexual differentiation, regulated by Sxl. It activates dsx female-specific splicing by promoting the formation of a splicing enhancer complex which consists of tra, tra2 and sr proteins [
].
This entry represents nucleocapsid proteins from the ssRNA viruses Tenuivirus and Phlebovirus [
,
]. These are ssRNA viruses. In crystal structures, the nucleocapsid protein from the Rift Valley fever virus (RVFV) displays a ring-shaped oligomeric assembly [
]. Electron microscopy (EM) also demonstrates that, in complex with RNA, the nucleocapsid protein forms rings in solution [].
Antigen I/II (Ag I/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrates, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Each of the polypeptides possesses seven structural regions, comprising a signal sequence, a highly charged N-terminal region, an alanine-rich repetitive domain (A region), a globular domain termed the V-domain based on the variability observed in this region between strains, a proline-rich repetitive region (P region), a C-terminal domain, and cell wall-anchoring sequences. proteins adopt a cell wall-anchored stalk structure formed by interactions between the intertwined A- and P-domains, which projects the V-domain containing a binding cleft away from the cell surface. This cleft may be used to promote streptococcal colonization of various tissues via both direct cellular adherence or interaction with extracellular matrix components [
,
,
].This entry represents the A region of alanine-rich repeats found in different species of Streptococcus, which forms a long α-helix that intimately intertwines into a left-handed supercoiled structure with the P repeat polyproline II (PPII) helix to form an unusually long and narrow stalk [
,
].
This family consists of several P-47 proteins from various Clostridium species [
] as well as related sequences from other bacteria. The function of this family is unknown.
Bleomycin-like antibiotic biosynthesis, pyrimidine ring methyltransferase
Type:
Family
Description:
This entry contains a radical SAM enzyme responsible for the methylation of the pyrimidine ring in bleomycin-like antibiotics, including bleomycin itself, zorbamycin and tallysomycin [
,
,
].
