Thiamine ABC transporter, ATP-binding protein ThiQ
Type:
Family
Description:
This entry represents the energy-transducing ATPase subunit ThiQ of the ThiBPQ thiamine (and thiamine pyrophosphate) ABC transporter in several proteobacteria. This protein is found so far only in proteobacteria, and is found in complete genomes only if the ThiB and ThiP subunits are also found.
BamE is part of the outer membrane protein (OMP) assembly Bam complex (composed of the outer membrane protein BamA, and four lipoproteins BamB, BamC, BamD and BamE), which is involved in assembly and insertion of β-barrel proteins into the outer membrane [
,
,
,
,
]. E. coli BamE is a nonessential member of the complex that stabilizes the interaction between the essential proteins BamA and BamD. It may modulate the conformation of BamA, likely through interactions with BamD [].
This entry represents a large family of polypeptides, the MFP (for membrane fusion protein) family. MFPs are a component of the RND family of transporters (RND refers to resistance, nodulation, and cell division). MFPs are proposed to span the periplasm in some way linking the inner and outer membranes [
]. However, some members of this family are found in Gram-positive bacteria, where there is no outer membrane. MFPs are involved in the export of a variety of compounds, from drug molecules to large polypeptides, and are united by their similar overall structural organisation, combined with some conserved regions []. This family includes:
Haemolysin secretion protein D (HlyD) from Escherichia coli.Lactococcin A secretion protein LcnD from Lactococcus lactis [
].RTX-I toxin determinant D from Actinobacillus pleuropneumoniae.Calmodulin-sensitive adenylate cyclase-haemolysin (cyclolysin) CyaD from Bordetella pertussis.Colicin V secretion protein CvaA from E. coli [
].Proteases secretion protein PrtE from Erwinia chrysanthemi [
].Alkaline protease secretion protein AprE from Pseudomonas aeruginosa [
].Several multidrug resistance proteins [
].
Thiol:disulfide interchange protein DsbD, N-terminal domain
Type:
Domain
Description:
Folding of secreted proteins within the periplasm of Escherichia coli requires the formation of disulfide bonds, a process that is dependent on the Dsb (disulfide bond) proteins. The reduction of Dsb proteins DsbC, DsbE, and DsbG occurs by transport of electrons from cytoplasmic thioredoxin to the C-terminal thioredoxin-like domain of DsbD (DsbDC). The N-terminal domain of DsbD (DsbDN) is capable of forming disulfides with oxidized DsbC, DsbE, or DsbG as well as with reduced DsbD [
]. This entry represents DsbDN [].
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 conserved site found in the extracellular solute-binding protein family 5 members from Gram-positive bacteria, Gram-negative bacteria and archaea.Family 5 members include: Periplasmic oligopeptide-binding proteins (gene oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (genes oppA, amiA or appA). Periplasmic dipeptide-binding proteins of Escherichia coli (gene dppA) and of Bacillus subtilis (gene dppE). Periplasmic murein peptide-binding protein of E. coli (gene mppA). Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzae. Periplasmic nickel-binding protein (gene nikA) of Escherichia coli. Heme-binding lipoprotein (gene hbpA or dppA) from H. influenzae. Lipoprotein xP55 from Streptomyces lividans. H. influenzae hypothetical protein HI0213. Hypothetical protein y4tO from Rhizobium sp. strain NGR234 symbiotic plasmid. Hypothetical protein y4wM from Rhizobium strain NGR234 symbiotic plasmid.
This domain appears to be the fist transmembrane region of the SecD export protein. SecD is directly involved in protein secretion and important for the release of proteins that have been translocated across the cytoplasmic membrane [
]. This domain is also found in modulator protein MzrA, which modulates the activity of the EnvZ/OmpR two-component regulatory system [].
Chordopoxvirus fusion protein/multifunctional envelope protein A27
Type:
Family
Description:
This is a family of viral fusion proteins from the Chordopoxvirinae. A 14kDa Vaccinia virus protein has been demonstrated to function as a viral fusion protein mediating cell fusion at endosmomal (low) pH [
]. The protein, found in the envelope fraction of the virions, is required for fusing the outermost of the two golgi-derived membranes enveloping the virus with the plasma membrane, and its subsequent release extracellularly. The N-terminal proximal region is essential for its fusion ability. More recently it has been shown that A27 forms disulfide-linked protein complexes with A26 protein providing an anchor for A26 protein packaging into mature virions. A27 regulates virion-membrane fusion rather than inducing it and is critical for the successful egress of mature virus particles [
].
This entry represents type IV secretion system proteins TraG and VirD4. TraG-like proteins are potential NTP hydrolases (NTPases) that are essential for DNA transfer in bacterial conjugation. They are thought to mediate interactions between the DNA-processing (Dtr) and the mating pair formation (Mpf) systems [
,
]. TraG-like proteins also function as essential components of type IV secretion systems of several bacterial pathogens. TraG is essential for DNA transfer in bacterial conjugation []. Agrobacterium tumefaciens VirD4 is essential for DNA transfer to plants []. VirD has been shown to have topoisomerase activity in vitro[
].
Methenyltetrahydromethanopterin hydrogenase cofactor biosynthesis protein HmdC
Type:
Family
Description:
Members of this protein family are HmdC, whose gene regularly occurs in the context of genes for HmdA (5,10-methenyltetrahydromethanopterin hydrogenase) and the radical SAM protein HmdB involved in biosynthesis of the HmdA cofactor. Bioinformatics suggests this protein, a homologue of eukaryotic fibrillarin, may be involved in biosynthesis of the guanylyl pyridinol cofactor in HmdA [
]. This entry also includes archaeal fibrillarin homologues also known as HcgG which is involved in biosynthesis of Iron-guanylylpyridinol (FeGP) cofactor [
].
This entry represents TraW, an essential component of the F-type conjugative transfer system for plasmid DNA transfer that has been shown to be localized to the periplasm [
,
].
This entry represents TrbI, an essential component of the F-type conjugative transfer system for plasmid DNA transfer that has been shown to be localized to the periplasm [
,
].
Members of this family are Gram-negative bacterial inner membrane proteins, generally designated ExbD, related to the TolR
. Members are always found next to a protein designated ExbB (
), which is related to the TolQ family (). ExbD and ExbB together form a proton channel through which they can harness the proton-motive force to energize TonB, which in turn energizes TonB-dependent receptors in the outer membrane. TonB-dependent receptors with known specificity tend to import siderophores or vitamin B12. A TonB system and Tol-Pal system often will co-exist in a single bacterial genome.
Members of this family are Gram-negative bacterial inner membrane proteins, generally designated ExbD, related to the TolR (
). Members are always encoded next to a protein designated ExbB (
), which is related to the TolQ (
). ExbD and ExbB together form a proton channel through which they can harness the proton-motive force to energize TonB, which in turn energizes TonB-dependent receptors in the outer membrane. TonB-dependent receptors with known specificity tend to import siderophores or vitamin B12. A TonB system and Tol-Pal system often will co-exist in a single bacterial genome.
Non-structural protein NSP4, C-terminal superfamily, coronavirus
Type:
Homologous_superfamily
Description:
This superfamily represents the C-terminal domain of the coronavirus nonstructural protein NSP4. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. Together with NSP3, NSP4 may play critical functions during viral RNA synthesis and double membrane vesicle formation [
,
]. It has been shown that in betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among betacoronavirus, which were demonstrated to be essential for membrane rearrangements during interaction with NSP3. This suggests that the specific details of the interaction between these two proteins varies among different coronavirus [,
]. This predominantly α-helical domain may be involved in protein-protein interactions [].
Protein phosphatase 1 regulatory subunit 26 (PPP1R26) interacts with and inhibits the phosphatase activity of protein phosphatase 1 (PP1) complexes [
]. The protein is widely expressed in multiple tissues in humans []. Although its exact biological function is not known, PPP1R26 may positively regulate cell proliferation, and has oncogenic characteristics - its expression in NIH3T3 fibroblasts has been shown to cause tumour development in nude mice [].
The TrbJ protein is found in the trb locus of Agrobacterium Ti plasmids where it is involved in the type IV secretion system for plasmid conjugative transfer [
,
]. TrbJ is a homologue of the F-type TraE protein (which is believed to be an inner membrane pore-forming protein (), as well as the vir system VirB5 protein [
].
This entry contains VirB11, a protein that is found in the vir locus of Agrobacterium Ti plasmids where it is involved in the type IV secretion system for DNA transfer [
]. VirB11 is believed to be an ATPase [] and is a homologue of the P-like conjugation system TrbB protein and the Flp pilus system protein TadA [].
Kinesin-like protein Kif23, Arf6-interacting domain superfamily
Type:
Homologous_superfamily
Description:
The C-terminal region of kinesin-like protein Kif23 (also known as MKLP1) is necessary for the interaction with the small GTPase Arf6. MKLP1 is a Flemming body-localising protein essential for cytokinesis. The Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane [
].
PR domain zinc finger protein 1 (PRDM1, also known as BLIMP-1) is a transcriptional repressor that is essential for cellular development. This entry includes BLIMP-1 from vertebrates and its homologues from invertebrates. In vertebrates, PRDM1 is also known as B lymphocyte-induced maturation protein 1 (BLIMP-1) or positive regulatory domain I-binding factor (PRDI-BF1). It is essential for the differentiation of B and T cells [
]. In Caenorhabditis elegans, it regulates the spatiotemporal cell migration pattern [
]. The degradation of PRDM1 by DRE-1/FBXO11-dependent mechanism regulates the C. elegans developmental timing and maturation [].
The tripartite ATP-independent periplasmic (TRAP) transport system is firmly established as a new type of extracytoplasmic solute receptor (ESR)-dependent uptake systems, unrelated to ABC transporters. In TRAP transport systems the driving force for solute accumulation is an electrochemical ion gradient and not ATP hydrolysis [
]. The first TRAP transporter to be characterised was the high-affinity C4-dicarboxylate transport (Dct) system from Rhodobacter capsulatus []. This consists of three proteins; an ESR (DctP) and small (DctQ) and large (DctM) integral membrane proteins.This entry represents a family of TRAP transporter permease proteins, including DctM, SiaM (involved in sialic acid uptake [
]) and YiaN (involved in the uptake of 2,3-diketo-L-gulonate [,
]).
This entry represents the VWA domain found in several bacterial cobalamin biosynthesis (CobT) proteins. CobT is involved in the transformation of precorrin-3 into cobyrinic acid [
].
Parvovirus non-structural protein 1, helicase domain
Type:
Domain
Description:
Parvoviruses are some of the smallest viruses containing linear, non-segmented single-stranded DNA genomes, with an average genome size of 5000 nucleotides. Parvoviruses have been described that infect a wide range of invertebrates and vertebrates and are well known for causing enteric disease in mammals. Genomes contain two large ORFs: NS1 and VP1; other ORFs are found in some sub-types and different gene products can arise from splice variants and the use of different start codons [
,
].This entry represents the helicase domain of the Parvovirus NS1 protein; which is required for viral DNA replication [
]. This domain contains the ATP/GTP-binding site motif A (P-loop). Parvoviral NS1 also regulates host gene expression through histone acetylation [].
Uncharacterised conserved protein UCP016175, prenyltransferase beta-subunit-related
Type:
Family
Description:
There is currently no experimental data for members of this group. However, they are distantly related to the beta subunits of protein prenyltransferases--protein farnesyltransferase (FTase) and protein geranylgeranyl transferase type II (GGTase-II). Protein prenyltransferases catalyse the posttranslational modification of cysteines by isoprenoid hydrocarbon chains [
]. The binding sites for both peptide and isoprenoid substrates reside primarily on the beta subunit of these enzymes [].
Cytochrome c-type biogenesis protein CcmB, bacteria
Type:
Family
Description:
This entry represents cytochrome c-type biogenesis protein CcmB (HelB) from bacteria. 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 [
].
Cell shape-determining protein MreD, proteobacterial type
Type:
Family
Description:
The MreD (murein formation D) protein is involved in bacterial cell shape determination [
,
]. Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.
This entry represents the proteobacterial MreD proteins.
This entry represents the alpha crystallin domain (ACD) found in mammalian Hsp27 (also denoted HspB1 in human).Small heat shock proteins (sHsps) are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits [,
]. They are characterised by the presence of an alpha crystallin domain (ACD) [].Hsp27 shows enhanced synthesis in response to stress. It is a molecular chaperone which interacts with a large number of different proteins. It is found in many types of human cells including breast, uterus, cervix, platelets and cancer cells. Hsp27 has diverse cellular functions including chaperoning, regulation of actin polymerization, keratinocyte differentiation, regulation of inflammatory pathways in keratinocytes, and protection from oxidative stress through modulating glutathione levels [
,
,
,
]. It is also a subunit of AUF1-containing protein complexes []. Hsp27 has been linked to several transduction pathways regulating cellular functions including differentiation, cell growth, development, and apoptosis []. Its activity can be regulated by phosphorylation. Its unphosphorylated state is a high molecular weight aggregated form (100-800kDa) composed of up to 24 subunits, which forms as a result of multiple interactions within the ACD, and is required for chaperone function and resistance to oxidative stress. Upon phosphorylation these large aggregates rapidly disassociate to smaller oligomers and chaperone activity is modified [].High constitutive levels of Hsp27 have been detected in various cancer cells, in particular those of carcinoma origin [
]. Over-expression of Hsp27 has a protective effect against various diseases-processes, including Huntington's disease []. Mutations in Hsp27 have been associated with a form of distal hereditary motor neuropathy type II and Charcot-Marie-Tooth disease type 2 [].
This entry represents the alpha crystallin domain (ACD) found in mammalian small heat shock protein (sHsp) HspB7, also known as cardiovascular small heat shock protein (cvHsp).Small Hsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits [
]. HspB7 is a 25kDa protein, preferentially expressed in heart and skeletal muscle []. It is essential for fetal heart development by modulating actin filament assembly []. It binds the cytoskeleton protein alpha-filamin (also known as actin-binding protein 280) []. The expression of HspB7 is increased during rat muscle aging []. As the human gene encoding HspB7 is mapped to chromosome 1p36.23-p34.3 it is a positional candidate for several dystrophies and myopathies [].
Glioma pathogenesis-related protein 1-like, SCP domain
Type:
Domain
Description:
This SCP-like extracellular protein domain is found in the glioma pathogenesis-related protein (GLIPR) subfamily, which consists of GLIPR1, GLIPR1-like 1 (GLIPR1L1), and GLIPR1-like 2 (GLIPR1L2). GLIPR1 and GLIPR1L2 are expressed in several tissues, whereas GLIPR1L1 is expressed predominantly in the testis and is involved in the binding of sperm to the oocyte complex [
,
].The SCP domain is also known as CAP domain [
]. The wider family of SCP containing proteins includes plant pathogenesis-related protein 1 (PR-1), CRISPs, mammalian cysteine-rich secretory proteins, which combine SCP with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. It has been proposed that SCP domains may function as endopeptidases.
The retroviral p12 protein is a proline rich virion structural protein found in the inner coat. p12 is associated with pathogenicity of the virus [
]. It is a constituent of the pre-integration complex (PIC) and mediates its integration [].
Starch-binding domain-containing protein 1, CBM20 domain
Type:
Domain
Description:
Starch-binding domain-containing protein 1 (STBD1), also known as Genethonin-1, is predicted to contain a hydrophobic N terminus, that allows it to associate with a cellular membrane structure, and a C-terminal CBM20 glycan binding domain. STBD1 is involved in glycogen metabolism by binding to glycogen and anchoring it to membranes, thereby affecting its cellular localization and its intracellular trafficking to lysosomes [
]. It has also been reported to interact with a known autophagy protein GABARAPL1, a member of the Atg8 family [].The CBM20 domain of STBD1 is crucial for its stability and ability to interact with glycogen-associated proteins [
].
Seminal vesicle protein II (SVP-II) [
] is one of the six major secretoryproteins secreted by rat seminal vesicle. It is a clotting protein that serves
as the substrate in the formation of the copulatory plug. Covalent clottingof this protein is catalyzed by a transglutaminase and involves the formation
of gamma-glutamyl-epsilon-lysine crosslinks. SVS-II sequence contains thirteenrepeats of a thirteen amino acid residue domain which is probably involved in
the cross-linking. There are a number of invariant residues in this signature,four of them (two lysines and two glutamines) probably participate in the
cross-links.
Chromobox protein homologue 3 (CBX3, also known as HP1 gamma) is a component of heterochromatin that binds histone H3 tails methylated at 'Lys-9' which leads to epigenetic repression [
]. By interacting with MIS12 complex, it is involved in the formation of a functional kinetochore []. It recruits NIPBL to sites of DNA damage at double-strand breaks []. It is a component of the E2F6.com-1 [] and PER [] complexes. The PER complex controls the circadian clock [].This entry represents the CHRomatin Organization Modifier (chromo) domain of CBX3.
Interleukin-1 receptor-associated kinase 1-binding protein 1/DUF541
Type:
Family
Description:
This entry represents a family of proteins from bacteria, archaea and animals, including Interleukin-1 receptor-associated kinase 1-binding protein 1 from mouse, which has been named SIMPL (signalling molecule that associates with mouse pelle-like kinase). SIMPL is a component of the IRAK1-dependent TNFRSF1A signaling pathway that leads to NF-kappa-B activation and is required for cell survival. It functions by enhancing RelA transcriptional activity [
,
]. Separate experiments demonstrate that a mouse family member (named LaXp180) binds the Listeria monocytogenes surface protein ActA, which is a virulence factor that induces actin polymerisation. It may also bind stathmin, a protein involved in signal transduction and in the regulation of microtubule dynamics []. In bacteria its function is unknown, but it is thought to be located in the periplasm or outer membrane.
NAC-alpha domain-containing protein 1, UBA-like domain
Type:
Domain
Description:
The biological function of NACAD remains unknown, but it shows high sequence similarity to the nascent polypeptide-associated complex (NAC) subunit alpha (NACA) that exists as part of several protein complexes playing a role in proliferation, apoptosis, or degradation. Like NACA, NACAD contains an NAC domain and a C-terminal ubiquitin-associated (UBA)-like domain. This entry represents the UBA-like domain of NACAD.
This is a group of cysteine peptidases which constitute MEROPS peptidase family C57 (clan CE). The type example is vaccinia virus I7 processing peptidase (vaccinia virus); protein I7 is expressed in the late phase of infection [
].A cysteine peptidase is a proteolytic enzyme that hydrolyses a peptide bond using the thiol group of a cysteine residue as a nucleophile. Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with members of each clan possessing a tertiary fold unique to the clan. Four clans of cysteine peptidases share structural similarities with serine and threonine peptidases and asparagine lyases. From sequence similarities, cysteine peptidases can be clustered into over 80 different families [
]. Clans CF, CM, CN, CO, CP and PD contain only one family.Cysteine peptidases are often active at acidic pH and are therefore confined to acidic environments, such as the animal lysosome or plant vacuole. Cysteine peptidases can be endopeptidases, aminopeptidases, carboxypeptidases, dipeptidyl-peptidases or omega-peptidases. They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid,
N-ethylmaleimide or
p-chloromercuribenzoate.
Clan CA includes proteins with a papain-like fold. There is a catalytic triad which occurs in the order: Cys/His/Asn (or Asp). A fourth residue, usually Gln, is important for stabilising the acyl intermediate that forms during catalysis, and this precedes the active site Cys. The fold consists of two subdomains with the active site between them. One subdomain consists of a bundle of helices, with the catalytic Cys at the end of one of them, and the other subdomain is a β-barrel with the active site His and Asn (or Asp). There are over thirty families in the clan, and tertiary structures have been solved for members of most of these. Peptidases in clan CA are usually sensitive to the small molecule inhibitor E64, which is ineffective against peptidases from other clans of cysteine peptidases [
].Clan CD includes proteins with a caspase-like fold. Proteins in the clan have an α/β/α sandwich structure. There is a catalytic dyad which occurs in the order His/Cys. The active site His occurs in a His-Gly motif and the active site Cys occurs in an Ala-Cys motif; both motifs are preceded by a block of hydrophobic residues [
]. Specificity is predominantly directed towards residues that occupy the S1 binding pocket, so that caspases cleave aspartyl bonds, legumains cleave asparaginyl bonds, and gingipains cleave lysyl or arginyl bonds.Clan CE includes proteins with an adenain-like fold. The fold consists of two subdomains with the active site between them. One domain is a bundle of helices, and the other a β-barrel. The subdomains are in the opposite order to those found in peptidases from clan CA, and this is reflected in the order of active site residues: His/Asn/Gln/Cys. This has prompted speculation that proteins in clans CA and CE are related, and that members of one clan are derived from a circular permutation of the structure of the other.Clan CL includes proteins with a sortase B-like fold. Peptidases in the clan hydrolyse and transfer bacterial cell wall peptides. The fold shows a closed β-barrel decorated with helices with the active site at one end of the barrel [
]. The active site consists of a His/Cys catalytic dyad.Cysteine peptidases with a chymotrypsin-like fold are included in clan PA, which also includes serine peptidases. Cysteine peptidases that are N-terminal nucleophile hydrolases are included in clan PB. Cysteine peptidases with a tertiary structure similar to that of the serine-type aspartyl dipeptidase are included in clan PC. Cysteine peptidases with an intein-like fold are included in clan PD, which also includes asparagine lyases.
Ectoine/Hydroxyectoine ABC transporter, substrate-binding protein EhuB
Type:
Family
Description:
This family represents the periplasmic substrate-binding proteins (PBPs) of ABC transport systems that are involved in the uptake of osmoprotectants (also termed compatible solutes) such as ectoine and hydroxyectoine. To counteract the efflux of water, bacteria and archaea accumulate the compatible solutes for a sustained adjustment to high osmolarity surroundings [
]. This family are an example of type 2 periplasmic binding fold proteins, which are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap [].This entry is named for one of the constituent proteins from Rhizobium meliloti (Sinorhizobium meliloti), involved in ectoine and 5-hydroxyectoine uptake, both for osmoprotection and for catabolism. The crystal structure of EhuB was solved in complex with either ectoine or 5-hydroxyectoine [
].
Periplasmic protein TorT, together with the TorS/TorR histidine kinase/response regulator system, regulates expression of the torCAD operon, which encodes the trimethylamine N-oxide (TMAO) reductase
system []. TorT appears to bind TMAO or related compounds, and is predicted to be involved in signal transduction and/or substrate transport []. TorT shows homology to a periplasmic D-ribose binding protein.
TDRD3 is a modular protein containing Tudor domain, a DUF/OB-fold motif and a ubiquitin-associated (UBA) domain [
]. It shows both nucleic acid- and methyl-binding properties and can interact with methylated RNA-binding proteins, such as fragile X messenger ribonucleoprotein 1 (FMRP) and DEAD/H box-3 (also known as DDX3X/Y, DBX/Y, HLP2 and DDX14) which is implicated in human genetic diseases []. At this point, TDRD3 may play a central role in RNA processing regulatory pathways involving arginine methylation. TDRD3 localizes predominantly to the cytoplasm stress granules (SGs) []. The Tudor domain is essential and sufficient for its recruitment to SGs [].
This domain is found in Zorya protein ZorC, a component of antiviral defense system Zorya type I, which confers resistance to phage infection. The function of ZorC is not clear but it may be involved in the sensing and inactivation of phage DNA, and if phage inactivation fails, the ZorAB proton channel opens up, leading to membrane depolarization and cell death [
]. This domain was described as EH_signature as it contains a strongly conserved glutamate at the N terminus and a histidine at the C terminus [], first described in a SWI2/SNF2 four gene operon []. Its strict-neighbourhood association with SWI2/SNF2 ATPase strongly suggests a function in conjunction with it []. The other genes in the operon are a OmpA protein and a TM protein []. This has a DNA related function along with the TerY-P triad [].
Nitrogen regulatory protein P-II, urydylation site
Type:
PTM
Description:
The P-II protein (gene glnB) is a bacterial protein important for the control of glutamine synthetase [
,
,
]. In nitrogen-limiting conditions, when the ratio of glutamine to 2-ketoglutarate decreases, P-II is uridylylated on a tyrosine residue to form P-II-UMP. P-II-UMP allows the deadenylation of glutamine synthetase (GS), thus activating the enzyme. Conversely, in nitrogen excess, P-II-UMP is deuridylated and then promotes the adenylation of GS. P-II also indirectly controls the transcription of the GS gene (glnA) by preventing NR-II (ntrB) to phosphorylate NR-I (ntrC) which is the transcriptional activator of glnA. Once P-II is uridylylated, these events are reversed.P-II is a protein of about 110 amino acid residues extremely well conserved. The tyrosine, which is uridylated, is located in the central part of the protein. In cyanobacteria, P-II seems to be phosphorylated on a serine residue rather than being uridylated. In the red alga, Porphyra purpurea, there is a glnB homologue encoded in the chloroplast genome. Other proteins highly similar to glnB include Bacillus subtilis protein nrgB [
]; and Escherichia coli hypothetical protein ybaI [].This entry represents a conserved stretch (in eubacteria) of six residues which contains the uridylated tyrosine.
Ubiquitin carrier protein 27 (UBC27), functions as a class II ubiquitin-conjugating (UBC) enzyme (E2). E2, together with E1 (ubiquitin-activating enzyme UBA) and E3 (ubiquitin ligase), is required in the multi-step reaction of ubiquitin conjugation. Unlike other Arabidopsis UBCs, in addition to an N-terminal ubiquitin-conjugating enzyme E2 catalytic domain (UBCc), UBC27 has an additional C-terminal ubiquitin-associated domain (UBA) [
]. This entry represents the UBA domain.
SynChlorMet cassette radical SAM/SPASM protein ScmE
Type:
Family
Description:
A biosynthesis cassette found in Syntrophobacter fumaroxidans MPOB, Chlorobium limicola DSM 245, Methanocella paludicola SANAE, and delta proteobacterium NaphS2 contains two PqqE-like radical SAM/SPASM domain proteins, a PqqD homologue, and a conserved hypothetical protein. These components suggest modification of a ribosomally produced peptide precursor, but the precursor has not been identified. This entry represents one of the two PqqE homologues of this cassette. It is more closely related to PqqE than the other homologue.
SynChlorMet cassette radical SAM/SPASM protein ScmF
Type:
Family
Description:
A biosynthesis cassette found in Syntrophobacter fumaroxidans MPOB, Chlorobium limicola DSM 245, Methanocella paludicola SANAE, and delta proteobacterium NaphS2 contains two PqqE-like radical SAM/SPASM domain proteins, a PqqD homologue, and a conserved hypothetical protein. These components suggest modification of a ribosomally produced peptide precursor, but the precursor has not been identified. This entry represents one of the two PqqE homologues of this cassette. It is more distantly related to PqqE than the other homologue.
Ribosomal protein L10, eubacterial, conserved site
Type:
Conserved_site
Description:
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L10 is one of the proteins from the large ribosomal subunit.
L10 is a protein of 162 to 185 amino-acid residues. This family only contains eubacterial members. These proteins have a conserved regionlocated in the N-terminal region.
Methylamine methyltransferase corrinoid protein reductive activase
Type:
Family
Description:
Members of this family occur as paralogues in species capable of generating methane from mono-, di-, and tri-methylamine. Members include RamA (Reductive Activation of Methyltransfer, Amines) from Methanosarcina barkeri MS (DSM 800) [
]. Member proteins have two C-terminal motifs with four Cys each, likely to bind one 4Fe-4S cluster per motif.
PEP-CTERM protein sorting domain, cyanobacterial subclass
Type:
Domain
Description:
This entry represents the PEP-CTERM protein sorting signals associated with bacterial exosortases. This entry is restricted to Cyanobacteria, including the genera Cyanothece, Nostoc, Trichodesmium, Lyngbya, Arthospira, etc. Cyanobacteria PEP-CTERM features strongly conserved residues within the transmembrane region, including a Gx4GxG motif. The corresponding cyanobacterial form of exosortase found in most species with this domain is described in
.
RPL27e has a KOW motif at its N terminus. KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4 [
].
Effector protein HopAB, BAK1-binding domain superfamily
Type:
Homologous_superfamily
Description:
HopAB family members are type III effector proteins that are secreted by the plant pathogen Pseudomonas syringae into the host plant to inhibit its immune system and facilitate the spread of the pathogen [
]. AvrPtoB, also called HopAB3, is the best studied member of the family. It suppresses host basal defenses by interfering with PAMP (pathogen-associated molecular signature)-triggered immunity (PTI) through binding and inhibiting BAK1, a kinase which serves to activate defense signaling []. It also recognizes the kinase Pto to activate effector-triggered immunity (ETI) [].AvrPtoB contains an N-terminal region that contains two kinase-interacting domains (KID) and a C-terminal E3 ligase domain. The first KID recognizes the PTI-associated kinase Bti9 as well as Pto, and is referred to as the Pto-binding domain (PID). The second KID interacts with BAK1 and FLS2, which are leucine-rich repeat-containing receptor-like kinases, and is called the BAK1-interacting domain (BID) [
,
]
. The family member HopPmaL is shorter and lacks the C-terminal E3 ligase domain [].This entry represents the second KID of AvrPtoB that binds to BAK1 thereby preventing its kinase activity after the perception of flagellin [
].
Cue2 contains two tandem CUE domains at the N terminus that may be involved in intramolecular monoubiquitination [
,
]. This entry represents the second CUE domain.
This family consists of several bacterial stage III sporulation protein AC (SpoIIIAC) and SpoIIIAD sequences. The exact function of this family is unknown. SpoIIIAD is an uncharacterised protein which is part of the spoIIIA operon that acts at sporulation stage III as part of a cascade of events leading to endospore formation. The operon is regulated by sigmaG [
].
Polyadenylate-binding protein-interacting protein 5/6/7, CUE domain
Type:
Domain
Description:
This entry represents the CUE domain found in a group of plant proteins, including CID5/6/7. CID7 contains an N-terminal PABC-interacting domain (PAM2 or PABP-interacting motif 2) which is also found in the human Paip1 and Paip2. It functions as an interaction partner of the PABC domain of Arabidopsis thaliana Poly(A)-binding proteins. It also harbours an ubiquitin-associated (UBA)-like CUE domain and a C-terminal small MutS-related (SMR) domain [
]. CID5 (also known as IPD1) has been shown to regulate the endocycle leading to hypocotyl elongation []. The biological function of CID6 is unclear.
Cue2 contains two tandem CUE domains at the N terminus that may be involved in the intramolecular monoubiquitination [
,
]. This entry represents the first CUE domain.
This entry represents the CUE domain found in fungal Cue3 proteins. Cue3 may be involved in the intramolecular monoubiquitination [
]. This domain can also be found in uncharacterised proteins from invertebrates.
This group represents an uncharacterised protein with a N-termial HtH domain and a C-terminal CBS domain pair. Proteins in this entry include transcriptional repressor CcpN from Bacillus subtilis. CcpN is a transcription repressor that binds to the promoter of gapB and pckA genes, preventing their expression. It acts as a regulator for catabolite repression of gluconeogenic genes [
].
This entry represents the first redox inactive TRX-like domain b found in protein disulfide-isomerase A4 (also known as ERp72). ERp72 exhibits both disulfide oxidase and reductase functions like PDI, by catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER and acting as isomerases to correct any non-native disulfide bonds [
,
]. It also displays chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins []. ERp72 contains three redox-active TRX (a) domains and two redox inactive TRX-like (b) domains. Its molecular structure is a'abb'a', compared to the abb'a' structure of PDI. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. Similar to PDI, the b domain of ERp72 is likely involved in binding to substrates.
Protein inscuteable homologue, LGN-binding domain superfamily
Type:
Homologous_superfamily
Description:
This is the LGN-binding domain (LBD) of the inscuteable homologue protein. It interacts with the TPR motifs of G-protein-signaling modulator 2 (GPSM2, also known as LGN) and stabilises LGN [
].
Guanine nucleotide-binding protein subunit gamma, fungal
Type:
Family
Description:
Yeast guanine nucleotide-binding protein subunit gamma (Ste18) is part of the G protein heterotrimer (made up of subunits alpha, beta and gamma) in the yeast pheromone response pathway. Receptor Ste2 is activated by mating pheromone, leading to GTP binding. This binding causes the beta and gamma subunits to dissociate from subunit alpha, with the resulting beta-gamma dimer functioning as the signal-transmitting component [
].
This entry contains the stage II sporulation protein D (SpoIID), which is a protein involved in the endospore formation program. SpoIID is one of the three genes (spoIID, spoIIM and spoIIP, [
,
,
]), under the control of sigma E, that have been shown to be essential for the engulfment of the forespore by the mother cell. Their products are involved in degradation of the septal peptidoglycan - mutations in spoIID, spoIIM or spoIIP block sporulation at morphological stage II, prior to the engulfment stage. These three genes are absolutely conserved (sometimes even duplicated) in all endospore formers [].
Sigma-E is important for the induction of proteins involved in heat shock response. RseA binds sigma-E via its N-terminal domain, sequestering sigma-E and preventing transcription from heat-shock promoters [
]. Activation of the the sigma(E)-dependent extracytoplasmic stress response requires the regulated proteolysis of RseA [], leading to an increase in the free pool of sigma(E) [].
DNA/RNA-binding protein KIN17, WH-like domain superfamily
Type:
Homologous_superfamily
Description:
Kin17 is a highly conserved protein that participates in DNA replication, DNA repair and cell cycle progression [,
,
].Region 51-160 of human Kin17 folds into an atypical winged helix (WH) domain. It consists of a three-α-helix bundle packed against a three-stranded β-sheet. Structural comparison with analogous WH domains reveals that Kin17 WH module presents an additional helix. In addition, helix H3 is not positively charged as in classical DNA-binding WH domains [
]. This domain may be involved in protein-protein interactions.
Bacterial type IV secretion systems mediate the transfer of macromolecular substrates into various target cells, including the transfer of virulence proteins into eukaryotic host cells. The virB operon constitutes a major determinant of virulence [
]. It mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. VirB-dependent changes of human endothelial cell (HEC) function include massive cytoskeletal rearrangements, a proinflammatory activation by nuclear factor NF-kappa-B, inhibition of early and late events of apoptosis, leading to an increased cell survival, and, at high infection doses, a cytostatic or cytotoxic effect, which interferes with a potent VirB-independent mitogenic activity [,
]. Protein PtlE is a component of the type IV secretion system ptl required for secretion of assembled pertussis toxin (a toxin from Bordetella pertussis) through the outer membrane [
,
,
]. PtlE has peptidoglycanase activity and is responsible for the local removal or rearrangement of the peptidoglycan layer during the assembly of the Ptl secretion complex [].
This superfamily includes bacterial coenzyme PQQ synthesis protein D (PqqD) domains. This protein is required for coenzyme pyrrolo-quinoline-quinone (PQQ) biosynthesis [
,
]. The function of PqqD is currently unknown, but has been speculated to play a role in releasing PQQ product from PqqC.
A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of
sequence similarities. One of these families includes yeast S7 (YS6); archaeal S4e; and mammalian and plant cytoplasmic S4 [
]. Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have
233 to 264 amino acids.This entry represents the central domain of these proteins.
The viral genome is translated into a single polyprotein of about 3000 amino acids. Generation of the mature non-structural proteins relies on the activity of viral proteases. Non-structural protein 2 (NS2) is an zinc-dependent autocatalytic endopeptidase which cleaves at the NS2/NS3 junction [
,
]. The action of NS3 proteinase (NS3P, ), which resides in the N-terminal one-third of the NS3 protein, then yields all remaining non-structural proteins.
NS2 belongs to MEROPS peptidase family C18 (hepatitis C virus endopeptidase 2, clan CM). The fold consists of two subdomains: an N-terminal helical domain and a C-terminal beta sheet. Peptidases are active as a homodimer and the two active sites are formed at the dimer interface by His and Glu from one monomer and Cys from the other [
].A cysteine peptidase is a proteolytic enzyme that hydrolyses a peptide bond using the thiol group of a cysteine residue as a nucleophile. Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with members of each clan possessing a tertiary fold unique to the clan. Four clans of cysteine peptidases share structural similarities with serine and threonine peptidases and asparagine lyases. From sequence similarities, cysteine peptidases can be clustered into over 80 different families [
]. Clans CF, CM, CN, CO, CP and PD contain only one family.Cysteine peptidases are often active at acidic pH and are therefore confined to acidic environments, such as the animal lysosome or plant vacuole. Cysteine peptidases can be endopeptidases, aminopeptidases, carboxypeptidases, dipeptidyl-peptidases or omega-peptidases. They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid,
N-ethylmaleimide or
p-chloromercuribenzoate.
Clan CA includes proteins with a papain-like fold. There is a catalytic triad which occurs in the order: Cys/His/Asn (or Asp). A fourth residue, usually Gln, is important for stabilising the acyl intermediate that forms during catalysis, and this precedes the active site Cys. The fold consists of two subdomains with the active site between them. One subdomain consists of a bundle of helices, with the catalytic Cys at the end of one of them, and the other subdomain is a β-barrel with the active site His and Asn (or Asp). There are over thirty families in the clan, and tertiary structures have been solved for members of most of these. Peptidases in clan CA are usually sensitive to the small molecule inhibitor E64, which is ineffective against peptidases from other clans of cysteine peptidases [
].Clan CD includes proteins with a caspase-like fold. Proteins in the clan have an α/β/α sandwich structure. There is a catalytic dyad which occurs in the order His/Cys. The active site His occurs in a His-Gly motif and the active site Cys occurs in an Ala-Cys motif; both motifs are preceded by a block of hydrophobic residues [
]. Specificity is predominantly directed towards residues that occupy the S1 binding pocket, so that caspases cleave aspartyl bonds, legumains cleave asparaginyl bonds, and gingipains cleave lysyl or arginyl bonds.Clan CE includes proteins with an adenain-like fold. The fold consists of two subdomains with the active site between them. One domain is a bundle of helices, and the other a β-barrel. The subdomains are in the opposite order to those found in peptidases from clan CA, and this is reflected in the order of active site residues: His/Asn/Gln/Cys. This has prompted speculation that proteins in clans CA and CE are related, and that members of one clan are derived from a circular permutation of the structure of the other.Clan CL includes proteins with a sortase B-like fold. Peptidases in the clan hydrolyse and transfer bacterial cell wall peptides. The fold shows a closed β-barrel decorated with helices with the active site at one end of the barrel [
]. The active site consists of a His/Cys catalytic dyad.Cysteine peptidases with a chymotrypsin-like fold are included in clan PA, which also includes serine peptidases. Cysteine peptidases that are N-terminal nucleophile hydrolases are included in clan PB. Cysteine peptidases with a tertiary structure similar to that of the serine-type aspartyl dipeptidase are included in clan PC. Cysteine peptidases with an intein-like fold are included in clan PD, which also includes asparagine lyases.
Outer membrane protein (OMP) assembly factor BamC is part of the outer membrane protein assembly Bam complex (composed of the outer membrane protein BamA, and four lipoproteins BamB, BamC, BamD and BamE), which is involved in assembly and insertion of β-barrel proteins into the outer membrane [
,
,
,
,
]. E. coli BamC is a nonessential member of the Bam complex that stabilises the interaction between the essential proteins BamA and BamD [].
The hypervariable region of the E2/NS1 region of Hepatitis C virus
varies greatly between viral isolates. E2 is thought to encode astructurally unconstrained envelope protein [
].
Stage III sporulation protein AH (SpoIIIAH) is a protein that is involved in forespore engulfment. It forms a channel with SpoIIIAH that is open on the forespore end and closed (or gated) on the mother cell end. This allows sigma-E-directed gene expression in the mother-cell compartment of the sporangium to trigger the activation of sigma-G forespore-specific gene expression by a pathway of intercellular signaling [
].
Uncharacterised conserved protein UCP033535, periplasmic lipoprotein
Type:
Family
Description:
There is currently no experimental data for members of this group of predicted periplasmic lipoproteins or their homologues, nor do they exhibit features indicative of any function.
Phage-like element PBSX protein XkdN-like superfamily
Type:
Homologous_superfamily
Description:
This entry is represents Phage-like element PBSX protein XkdN from Bacillus subtilis (strain 168) and similar proteins predominantly found in Firmicutes and some tailed bacteriophages. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches. Members of this group of proteins are chaperones involved in phage tail assembly [
,
] and have been predicted to form a spiral structure [].
Proteins in this entry may be the encapsulin shell protein in a type 4 A-domain encapsulin nanocompartment system. Its cargo may be upstream glyceraldehyde-3-phosphate dehydrogenase [
]. It has been shown that bacterial/archaeal encapsulin-like systems and HK97-type viruses share a common ancestor and it is likely that encapsulins have evolved from HK97-type phages.
The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
]. EpsH is one of the minor pseudopilin components of the type II secretion system (T2SS). Its structure has been revealed [
].
Members of this protein family occur strictly in the presence of a peptide modification radical SAM enzyme and some small peptide in which, for a stretch, every fourth amino acid is Cys. Cysteine residues usually are flanked by residues with sterically small side chains, as with many radical SAM-modified peptides [
].
Putative ABC transporter PGF-CTERM-modified substrate-binding protein
Type:
Family
Description:
Members of this archaeal protein family resemble periplasmic substrate-binding proteins of ABC transporters and appear in gene neighbourhoods with permease and ATP-binding cassette proteins. Studies suggest that one family member (
) is part of the ABC transporter complex BtuCDF involved in cobalamin (vitamin B12) import [
]. Notably, essentially all members also have the PGF-CTERM putative protein-sorting domain at the C terminus, while more distant homologues instead have what appear to be lipoprotein signal peptides at the N terminus.
This entry represents the RING zinc finger domain of 'RING finger protein Z', a small polypeptide found in some negative-strand RNA viruses including Lassa fever virus, which plays a crucial role in virion assembly and budding. RING finger Z has been shown to interact with several host proteins, including promyelocytic leukemia protein and the eukaryotic translation initiation factor 4E [
,
]. It is sufficient in the absence of any other viral proteins to release virus-like particles from the infected cell []. This protein is also responsible for arenavirus superinfection exclusion; expression of this protein in a host cell strongly and specifically inhibits areanavirus transcription and replication [].The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions [
,
,
]. There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger'. The RING domain is a protein interaction domain which has been implicated in a range of diverse biological processes. Several 3D-structures for RING-fingers are known [
,
]. The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. The spacing of the cysteines in such a domain is:C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C
Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second.
This entry describes the DndE protein encoded by an operon associated with a sulphur-containing modification to DNA (phosphorothioation)[
]. The operon is sporadically distributed in bacteria, much like some restriction enzyme operons. DndE is part of a protein complex that also includes IscS, DndC, and DndE, involved in phosphorothioation (PT) []. DndE binds to DNA in vitro, with a preference for nicked dsDNA [], but its nicked dsDNA-binding capacity does not seem essential for PT modification [].
This entry represents a paralogous family, in Syntrophus aciditrophicus SB, of peptides with a conserved N-terminal region followed by ten to seventeen direct repeats of the sequence CXXX.
This entry represents the EVE domain of thymocyte nuclear protein 1 from mammals [
] and its orthologue from S. pombe. This entry also includes uncharacterised sequences from bacteria and archaea.
Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [
]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase []. There are at least two distinct cobalamin biosynthetic pathways in bacteria [
]:Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [
]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [
,
]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii. Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [
]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans.This entry represents the integral membrane protein CbiM, which forms part of the energy-coupling factor (ECF) transporter complex CbiMNOQ that is involved in cobalt import [
,
], and plays a role in the cobalamin synthesis pathway.
This entry represents the protein component 3 of ribonuclease P. RNase P is a protein complex that functions in the processing of pre-tRNA, generating mature tRNA molecules by cleaving their 5'-ends. It consists of a RNA moiety and at least 4 protein subunits. Unlike most other natural ribozymes, it recognises and cleaves its substrate in trans [
].
SciN (also known as Lip) is a lipoprotein tethered to the outer membrane and expressed in the periplasm of E. coli, and is essential for T6SS-dependent secretion of the Hcp-like SciD protein and for biofilm formation [
].
p53 and DNA damage-regulated protein 1 (PDRG) mRNA is upregulated by ultraviolet radiation (UV) but downregulated by tumour suppressor p53 []. Its expression is increased in multiple human malignancies, suggesting that it could play a role in cancer development and/or progression []. It belongs to the prefoldin subunit beta family, whose members are chaperone complex subunits. The function of PDRG is not clear.
