This entry represents a domain found in proteobacteria, including the type VI secretion system (T6SS) immunity protein TsiT from Pseudomonas aeruginosa (
), which belongs to the Imm52 family. This protein can suppress the virulence of TseT [
]. TsiT adopts a β-sandwich fold with nine α-helices and an eight-stranded antiparallel central β-sheet. It has a large electro-negative pocket with hydrophobic surroundings that play a role in the interaction with TseT [,
]. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-REase-5 family [].
The gene III product of cauliflower mosaic virus (CaMV) is known as virion-associated protein or P3 [
], which is tightly associated with the virus particles and has a regulatory function in the virus infection cycle. P3 decorate the virions; its N-terminal domain forms an antiparallel α-helical coiled-coil network at the surface and the C-terminal domain interacts with the C-terminal half of the viral coat protein []. It is a DNA binding protein in which the DNA binding activity is located on its C-terminal part []. A family of related proteins is expressed by other members of the Caulimoviridae.
This entry represents immunity proteins with an alpha+beta fold and a conserved arginine. The family includes immunity factor for TNT (IFT) from Mycobacterium tuberculosis. This bacteria uses tuberculosis necrotizing toxin (TNT) to kill human macrophages; the immunity factor IFT binds TNT and inhibits its activity to prevent self-poisoning [
].
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved [DE]R motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox13 or Ntox40 families []. In some proteins this domain is fused to the Imm38 () immunity domain.
This entry represents a predicted immunity protein with a mostly α-helical fold and conserved aspartate and cysteine residues and an SE motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the LD-peptidase or Tox-Caspase families [
].
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved tryptophan and Dx[DE] motif. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-RES or Tox-URI1 families. Proteins containing this domain are present in heterogeneous polyimmunity loci in polymorphic toxin systems [].
This entry represents a predicted immunity protein with a mostly α-helical fold and conserved arginine and phenylalanine residues. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox48 family [
]. This domain is often fused to the Imm72 immunity domain.
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved DxEA motif and arginine residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-ColD family [
].
Polymorphic toxins systems consist of secreted toxins, primarily involved in
intra-specific conflict between related strains of prokaryotes. These toxins are as a rule multi-domain and tend to vary their toxin domains through a process of recombination that might replace an existing toxin domain by a distinct one encoded by standalone cassettes, therefore their name as polymorphic toxins. A key feature that distinguishes the polymorphic toxins from conventional toxins (whose primary targets are in distantly related organisms) is the presence of immunity proteins.This entry represents a predicted immunity protein with an alpha+beta fold and a conserved E+G and ExxY motifs. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Ntox40, Tox-CdiAC and Tox-ARC families [
]. The protein is also found in polyimmunity loci in polymorphic toxin systems.
This entry represents a predicted immunity protein with an all-beta fold. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-HHH or Ntox24 families [
].
This entry represents a predicted immunity protein with an alpha+beta fold. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox18 family [
].
This entry represents a predicted immunity protein with an alpha+beta fold and a conserved SF motif and tryptophan residue. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Ntox21, Ntox29 or Tox-ART-RSE-like ADP-ribosyltransferase families [
].
Bone gamma-carboxyglutamic acid protein (BGP), also known as osteocalcin, and matrix gamma-carboxyglutamic acid protein (MGP) are the only vitamin K-dependent
proteins that have been isolated from bone. MGP is a small protein found in bone, dentin and cartilage. It contains five gamma-carboxyglutamic acid (Gla) residues (formed by post-translational modification of glutamic acid by vitamin K-dependent carboxylase) and a single disulphide bond. BGP is a 49 residue protein found in bone. It contains three Gla residues and a single disulphide bond. There is little similarity between these vitamin K-dependent bone proteins and the blood coagulation proteins, though they are believed to have diverged from a common ancestor [].
Matrix Gla protein associates with the organic matrix of bone and cartilage. It is thought to act as an inhibitor of calcification [
]. Defects in MGP are the cause of Keutel syndrome (KS). KS is an autosomal recessive disorder characterised by abnormal cartilage calcification, peripheral pulmonary stenosis neural hearing loss and midfacial hypoplasia [].
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human [
]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].This entry represents a protein encoded by the bacteriophage T7 early gene 0.7. This gene is dispensible in a fast-growing host, but is essential when the host is growing suboptimally. The protein is bifunctional, with the C-terminal third involved in host transcription shut-off, while the N-terminal two-thirds has protein kinase activity and is capable of phosphorylating a number of host cell proteins and itself [
]. Expression of the protein kinase in the host leads to the phosphorylation of host RNAse E and the stabilisation of phage mRNA.
This entry represents a family of exosortase-related proteins. Exosortases are proposed transpeptidases with a cysteine active site (3.4.22.-), but usually are associated with specific C-terminal target motifs (PEP-CTERM, PEF-CTERM, PGF-CTERM, etc) [
].
This protein family occurs in the seadornavirus virus group, with designations VP8 in Banna virus, and VP9 in Kadipiro virus and Liao ning virus [
]. VP8 from Banna virus is part of the inner core, within the outer coat of the virus. The inner core contains VP1, VP2, VP3, VP8 and VP10, with VP8 forming the core-surface layer, an icosahedral capsid with a T=13 symmetry, consisting of 230 trimers [].
This protein family occurs in the seadornavirus virus group, with designation VP4 in Banna virus, Kadipiro virus, and Liao ning virus [
]. Although this family has been suggested to resemble methyltransferases, members show apparent N-terminal sequence similarity to the outer capsid protein VP5 of the orbivirus group, such as bluetongue virus, which also belong to the Reoviridae.
Members of this protein family are outer membrane proteins (OMP), as can be seen by their homology to YfaZ protein [
] and by the OMP targeting region at the C terminus, including a C-terminal Phe residue. Members of this protein family are found in the great majority of genomes with the GlyGly-CTERM protein sorting signal and the rhombosortase putative sorting enzyme, although the relationship may be fortuitous.
This protein family occurs in the seadornavirus virus group, with designations VP5 in Banna virus, and VP6 in Kadipiro virus and Liao ning virus. The function is unassigned [
].
This protein family occurs in the seadornavirus virus group, with designations VP11 in Banna virus, and VP12 in Kadipiro virus and Liao ning virus [
]. The function has not been assigned.
Members of this protein family are VP3 proteins in the seadornavirus group [
]. They display sequence similarity to methyltransferases. Viral guanylyltransferase VP3 from Banna virus is an outer capsid protein involved in mRNA capping, catalysing the final three activities (RNA guanylyltransferase, RNA-7N-methyltransferase and RNA-2'O-methyltransferase) required for the formation of 5' cap structure [].
Na
+/Ca
2+exchange proteins are involved in maintaining Ca
2+homeostasis in
a wide variety of cell types. They are found in both the plasma membraneand intracellular organellar membranes, where they exchange Na
+for Ca
2+in
an electrogenic manner. When located in the plasma membrane, they generallyutilise the transmembrane (TM) Na
+concentration gradient in order to
extrude Ca2+from cells. Three mammalian isoforms have been cloned to date
(NCX1-3), which consist of 920-970 amino acid residues that are predictedto possess 11 or 12 TM domains. Interestingly, they possess a short motif
(~30 residues) that is similar to the Na+/K
+-ATPase, although its function
is unknown [,
].NCX1 has been found to be predominantly expressed in the heart, where it
plays an important role in excitation-contraction coupling, but it is alsoabundant in a variety of other tissues [
]. NCX2 and NCX3 transcripts havebeen detected in the brain and skeletal muscle [
,
]. Homologous Na+/Ca
2+exchange proteins have also been found in Caenorhabditis elegans, Drosophila melanogaster andLoligo opalescens (California market squid).
This entry represents YtaF, which represents a protein family identified, at the time of the publication of the Carboxydothermus hydrogenoformans genome. The phylogenetic profile of the members matches the subset of the Firmicutes capable of forming endospores. These species include Bacillus anthracis, Clostridium tetani, Thermoanaerobacter tengcongensis, and Geobacillus kaustophilus.
Centromere protein W (CENP-W) is a component of the CENPA-NAC (nucleosome-associated) complex, which plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation [
]. CENP-W gene is up-regulated in various types of cancers and was first identified as a putative oncogene, CUG2 []. It can be regulated by CSN5, a component of the CSN complex involved in protein degradation via the ubiquitin-proteasome pathway []. The DNA-binding regions in CENP-T or CENP-W is essential for inducing positive supercoils into DNA and for the kinetochore targeting of the CENP-T-W-S-X complex [].
This group of proteins includes two protein families: caldesmon and lymphocyte specific protein.Caldesmon (CDM) is an actin- and myosin-binding protein implicated in the
regulation of actomyosin interactions in smooth muscle and non-muscle cells,possibly acting as a bridge between myosin and actin filaments [
]. CDM isbelieved to be an elongated molecule, with an N-terminal myosin/calmodulin-
binding domain and a C-terminal tropomyosin/actin/calmodulin-binding domain,separated by a 40nm-long central helix [
].A high-molecular-weight form of CDM is predominantly expressed in smooth
muscles, while a low-molecular-weight form is widely distributed in non-muscle tissues and cells (the protein is not expressed in skeletal muscle
or heart).
Proteins in this entry, exemplified by YtfJ of Bacillus subtilis, are encoded by bacterial genomes if, and only if, the species are capable of endospore formation. YtfJ was confirmed in spores of B. subtilis; it appears to be expressed in the forespore under control of SigF [
].
Rsr1 is a member of the Rap subfamily of the Ras family that is found in fungi. In budding yeasts, Rsr1 is involved in selecting a site for bud growth on the cell cortex, which directs the establishment of cell polarization. The Rho family GTPase cdc42 and its GEF, cdc24, then establish an axis of polarized growth by organizing the actin cytoskeleton and secretory apparatus at the bud site. It is believed that cdc42 interacts directly with Rsr1 in vivo [
,
]. In filamentous fungi, polar growth occurs at the tips of hypha and at novel growth sites along the extending hypha. In Ashbya gossypii, Rsr1 is a key regulator of hyphal growth, localizing at the tip region and regulating in apical polarization of the actin cytoskeleton [].Most Ras proteins contain a lipid modification site at the C terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins [
].
This entry includes Rap2a/b/c, which is part of the Rap subfamily of the Ras family. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton [
,
]. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments []. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway []. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis []. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation []. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras [].Most Ras proteins contain a lipid modification site at the C terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins [
].
RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share >98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C terminus []. RabL2 plays an important role in trafficking of ciliary GPCRs at the ciliary base in mammalian cells []. RabL2 has been shown to be involved in male fertility, sperm intra-flagellar transport, and tail assembly []. Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins [
,
].
GRIP1-associated protein 1 (GRIPAP1, also known as GRASP-1) is expressed in the CNS and interacts with GRIP1, GRIP2 and AMPA receptors [
]. It may regulate neuronal ras signaling and contribute to the regulation of AMPA receptor distribution by NMDA receptor activity [].
Proteins in this entry belong to the broader family of PRC-barrel domain proteins, but are found only in endospore-forming bacteria within the Firmicutes (low-GC, Gram-positive bacteria). Most species encode two of these proteins, though their function is unknown. In Bacillus subtilis, which encodes YlmC and YmxH, YmxH is strongly induced by the mother cell-specific sigma-E factor [
].
Proteins in thie entry, typified by YpjB, are restricted to a subset of the endospore-forming bacteria which includes Bacillus species, but not species. In Bacillus subtilis, ypjB was found to be part of the sigma-E regulon [
]. Sigma-E is a sporulation sigma factor that regulates expression in the mother cell compartment. Null mutants of ypjB show a sporulation defect, but this gene is not, however, a part of the endospore formation minimal gene set.
SdpI is an immunity protein that provides protection for the cell against the toxic effects of its own SdpC killing factor and that functions as a receptor/signal transduction protein as well. It responds to the SdpC toxin by sequestering the SdpR autorepressor at the membrane. Sequestration relieves repression and stimulates synthesis of immunity protein [
].
This family of proteins includes the SdpI and YhfL proteins from Bacillus subtilis. The SdpI protein is a multipass integral membrane protein that protects toxin-producing cells from being killed. Killing is mediated by the exported toxic protein SdpC an extracellular protein that induces the synthesis of an immunity protein [
].
Periplasmic L-arabinose-binding protein (ABP) is involved in the high-affinity L-arabinose membrane transport system. It binds with high affinity to arabinose, but can also bind D-galactose (at approximately 2-fold lower affinity) and D-fucose (at approximately 40-fold lower affinity) [
,
].The periplasmic ABP consists of two alpha/beta globular domains connected by a three-stranded hinge, a Venus flytrap-like domain, which undergoes a transition from an open to a closed conformational state upon ligand binding. Moreover, ABP is homologous to the ligand-binding domain of eukaryotic receptors such as metabotropic glutamate receptor (mGluR) and DNA-binding transcriptional repressors such as LacI and GalR [
].
Glycosyltransferase-stabilising protein GtfB, together with GtfA, forms a two-protein enzyme complex that is involved in glycosylation. GtfB stabilises the glycosylation activity of GtfA, causing it to partially localise to the cellular membrane where it is more protease resistant [
,
,
].
Faithful chromosome segregation depends on the opposing activities of the budding yeast Glc7/PP1 protein phosphatase and Ipl1/Aurora protein kinase. It is believed that Glc7 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets (rather than regulating the Ipl1 kinase) [
].Gip3 and Gip4 have been identified amongst several genes as ipl1 dosage suppressors, and encode proteins that physically interact with Glc7 [
]. Over-expression of the GIP3 and GIP4 suppressors was shown to alter Glc7 localisation, indicating they are previously unidentified Glc7 regulatory subunits, and that Gip3 and Gip4 over-expression may impair Glc7's mitotic functions. It has been proposed, therefore, that over- expression of Glc7 regulatory subunits can titrate Glc7 away from relevant Ipl1 targets, thereby suppressing ipl1-321 cells by restoring the balance of phosphatase/kinase activity [].
Bcl-2-related protein A1 is a proapoptotic member of the Bcl-2 family. It retards apoptosis induced by IL-3 deprivation []. It may function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection
This family of proteins includes the adenosine monophosphate-protein transferase SoFic from Shewanella oneidensis (
). Family members contain a fido domain that mediates the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins [
].
Proteins in this entry contain a fido domain. The domain is named after the Fic and Doc proteins where it is found. Included in this entry are adenosine monophosphate-protein transferase Fic and FICD. Both Fic and FICD add adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), or remove the same modification from target proteins (de-AMPylation), depending on whether cells are in a resting state or stressed [
]. Both bind divalent cations, preferring Mn2+over Mg
2+[
]. The adenosine monophosphate-protein transferase SoFic from Shewanella oneidensis is known only to add AMP to target proteins, either at Tyr or Thr residues [].
Disruption of the V2 gene in Tomato yellow leaf curl virus (TYLCV) stopped its ability to systemically infect Solanum lycopersicum (Tomato) (Lycopersicon esculentum) plants, suggesting that the V2 gene product is required for successful infection
of the host [].
The tospovirus genome consists of three linear ssRNA segments,
denoted L, M and S complexed with the nucleocapsid protein.The S RNA encodes the nucleocapsid protein and another
non-structural protein [].
ARL14 effector protein (also known as ARF7 effector protein) interacts with actin based motor protein myosin 1E (MYO1E) and may be involved in connecting MHC class II-containing cytoplasmic vesicles to the actin network in dendritic cells [
].
Poliovirus infection leads to drastic alterations in membrane permeability late during infection. Proteins 2B and 2BC enhance membrane permeability [
,
].
This family represents a group of bacterial and fungal sequences homologous to the uncharacterized protein YjlB from B. subtilis, whose function is not yet known. These proteins contain a conserved cupin domain.
Members of this family are found in the bromoviridae, assembling into long tubular structures at the surface of the infected protoplast. These
proteins aid the infection of the virus [,
].
This family consists of conserved hypothetical proteins from Borrelia burgdorferi (Lyme disease spirochete)
, some of which are putative plasmid partition proteins [].
Staphylococcus aureus pathogenicity islands (SaPIs) are highly mobile phage-related pathogenicity islands that typically carry genes for one or more superantigens. They are the primary cause of superantigen-induced diseases, especially toxic shock syndrome. SaPIs are induced to excise and replicate by the presence of a temperate phage. The SaPI then induces the phage to produce special small capsids into which it is encapsidated, resulting in exteremly high transfer frequences [
].This entry represents the SaPI CP3 protein, which is involved in the morphogenesis of the characteristic small SaPI capsids [
].
This entry represents the matrix protein M from negative-strand Bornaviridae viruses (BDV-M). Its most stable oligomeric form is a tetramer, and it lies beneath the viral envelope where it associates with the inner layer of the viral membrane. It bridges the gap between the nucleocapsid and the viral envelope thereby imparting structural integrity and individual form to the virus particle. Borna disease virus (BDV) is a neurotropic enveloped RNA virus causing a noncytolytic, persistent infection of the central nervous system in mammals. The order to which this virus belongs, Mononegavirales, also contains the Ebola, mumps, rabies and measles viruses, amongst other highly infectious agents [
].Structural studies on this protein have shown that heterologously expressed BDV-M co-purifies with and protects ssRNA oligonucleotides taken up from the expression host. This has revealed the ability of BDV-M to bind RNA and lipid membranes simultaneously, thus expanding the repertoire of M-protein functionalities [
].
This family includes FlgO from Vibrio cholerae, which is part of an operon with two genes, flgO and flgP, positively regulated by FlrC, the activator of class III flagellar genes [
]. FlgO and FlgP function in motility to mediate flagellar stability and influence attachment and colonization [].
These vegatative storage proteins are close relatives of the plant acid phosphatases (
) and are limited to members of the Phaseoleae including Glycine max (Soybean) and Phaseolus vulgaris (Kidney bean). These proteins are highly expressed in the leaves of repeatedly depodded plants [
,
]. Vegetative storage protein (VSP) differs most strikingly from the acid phosphatases in the lack of the conserved nucleophilic aspartate residue in the N terminus, thus, they should be inactive as phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the G. max VSP. In 1994 this assertion was refuted by the separation of the activity from the VSP [].
The IraM protein was originally named enhancing lycopene biosynthesis protein 1 on the basis of its ability to restore lycopene production in mutants [
]. It has subsequently been shown that this protein inhibits rpoS proteolysis by regulating rssB activity, thereby increasing the stability of the sigma stress factor rpoS during magnesium starvation [].
Members of this protein family are found exclusively in the Cyanobacteria, usually usually encoded next to and in at least one case fused to a gene encoding cyanoexosortase A.
Members of this protein family are always found next to an exosortase/archaeosortase-like protein, and occur so far only in the flavobacteria, within the Bacteroidetes. Members do not have an obvious PEP-CTERM-like C-terminal protein sorting domain [
].
Verrucomicrobia /Planctomycetes-restricted protein
Type:
Family
Description:
Members of this protein family are extremely lineage-restricted, occurring exclusively in the Planctomycetes and Chlamydiae/Verrucomicrobia group, although not in Chlamydia itself. The function is unknown; the lack of invariant residues other than a single Phe suggests an ancient, conserved, non-enzymatic role.
This entry represents essentially the full length, ~60 residues, of a two-gene paralogous family from Acidobacterium sp. MP5ACTX8. Sequences consist of an N-terminal signal sequence ending in a GC motif, suggestive of the lipoprotein signal sequence, followed immediately by a C-terminal domain sequence with characteristics PEP-CTERM-like sequences, including a PExP motif and a transmembrane helix. Both members occur next to the novel exosortase variant, XrtJ, which contains a novel C-terminal domain [
].
Members of this protein family are exclusive to archaea, probably all of which have S-layer surface protein arrays. All member proteins have an N-terminal signal sequence. The majority of known members belong to codirectional tandem arrays in the genus Methanosarcina (nine in M. barkeri str. Fusaro). Nearly all members have an additional 50 residues, consisting of low-complexity sequence rich in E,N,Q,T,S, and P, followed by a variant (PAF) form of the PGF-CTERM putative archaeal surface glycoprotein sorting signal. The coined name, sarcinarray family protein, evokes the predicted archaeal surface layer localisation, the taxonomic bias of known members, and the tandem organisation of most members.
This family consists of the N-terminal region of geminivirus
C4 or AC4 proteins. In Tomato yellow leaf curl virus the C4 protein is necessary for efficient spreading ofthe virus in Solanum lycopersicum (Tomato) (Lycopersicon esculentum) [
].
This entry includes Gp45 from bacteriophage Mu. Gp45 is a component of the baseplate that forms a central needlelike spike used to puncture the host cell membrane for tube insertion during virus entry. It serves as the distal plug of tail tube channel and might regulate the process of the phage DNA and protein ejection into the host cell [
,
]. The characteristics of the protein distribution suggest prophage matches.
This protein family, with average protein length about 58 residues, occurs in several marine bacteria, such as Shewanella benthica KT99, Marinobacter sp. ELB17, and Photobacterium profundum 3TCK. The striking feature is a C-terminal motif CCGSCS, which (perhaps coincidentally) resembles conserved core motif [LC]CGSC shared by two methanobactin precursors .
This entry represents the coat proteins of the leviviruses (phage MS2) and alloleviruses (phage Qbeta and phage F1). The Levivirus coat protein forms the bacteriophage coat that encapsidates the viral RNA. The virion shell is formed from 180 copies of this protein. The Bacteriophage MS2 coat protein controls two distinct processes: sequence-specific RNA encapsidation and repression of replicase translation by binding to an RNA stem-loop structure of 19 nucleotides containing the initiation codon of the replicase gene. The binding of a coat protein dimer to this hairpin shuts off synthesis of the viral replicase, switching the viral replication cycle to virion assembly rather than continued replication [
].
Protein male-specific lethal-1 (Msl-1) is a component of a multisubunit histone acetyltransferase complex (MSL). The MSL complex has histone acetyltransferase (HAT) activity with specificity towards histone H4 lysine 16 [
]. In fruit fly, the MSL proteins are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation). It has been shown that Msl-1 is associated with hundreds of discrete sites along the length of the X chromosome in males and not in females, and is also associated with 10-20 autosomal sites in males in fruit fly [].In humans the MSL complex has the same specificity for acetylating lysine 16 on histone H4, but in contrast to the Drosophila complex, the hMSL complex targets
all chromosomes in vivo []. In mammals the Msl-1 homologue is also known as hampin [].
SMAP (small acid protein) family consists of small (~20kDa) glutamic acid-rich or aspartic acid-rich proteins. Homologues are known from metazoa and fungi.
Spermatogenesis-associated protein 3 (SPATA3) is strongly expressed in testis in mice. It may have potential roles in spermatogenesis cell apoptosis or spermatogenesis [
].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents Cas1, which is a metal-dependent DNA-specific endonuclease [
]. Cas1 may play a role in the recognition, cleavage, and/or integration of foreign nucleic acids into CRISPRs.
Kizuna (is a Japanese word meaning "bond") is a centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. It is required for stabilising the expanded pericentriolar material around the centriole [
]. It can be regulated through phosphorylation by polo-like kinase 1 (Plk1) [].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents a family of Cas proteins, including the Cas7 (also known as DevR) protein from Myxococcus xanthus. Cas7 is a key regulators of development, and mutants of DevR are incapable of fruiting body development [
]. The expression of Cas7 appears to be regulated through a number of means, including both location and autorepression.
This entry includes ribosomal protein S1 (RPS1) and related proteins, such as 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH) and general stress protein 13 (YugI) from
Bacillus subtilis, which has an S1 domain and a conserved RNA binding surface [
].The bacterial RPS1 consists of 4-6 tandem S1 domains [
]. In some bacteria, the tandem S1 array is located C-terminal to a 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HMBPP reductase) domain. While RPS1 is found primarily in bacteria, proteins with tandem RPS1-like domains have been identified in plants and humans, however these lack the N-terminal HMBPP reductase domain.
CEP162 (KIAA1009/QN1) is required for ciliogenesis. It is an axoneme-recognition protein that promotes and restricts transition zone formation at the cilia base. It has also been shown to interact with CEP290 and mediate its association with microtubules [
].
Bombesin receptor-activated protein (BRAP, C6orf89) is an important regulator of immune and inflammatory responses in the human airway epithelium [
]. BRAP interacts with the orphan G protein-coupled bombesin receptor subtype 3 []. BRAP is widely expressed in human airway epithelial cells and vascular endothelial cells. It regulates NF-kB activity by enhancing histone deacetylase (HDAC) activity [].
This entry represents the tubulin-like proteins FtsZ and CetZ. FtsZ is a homologue of eukaryotic tubulin and is essential in the process of cell division; it forms a contractile ring structure (Z ring) at the future cell division site. The regulation of the ring assembly controls the timing and the location of cell division. One of the functions of the FtsZ ring is to recruit other cell division proteins to the septum to produce a new cell wall between the dividing cells [
,
,
].Homologous from plants, such as AtFtsZ2-1, AtFtsZ1 and AtFtsZ2-2 are components of the plastid division machinery that forms a contractile ring at the division site and are required for plastid division in a dose-dependent manner [
]. Cetz, an archaeal tubulin-like protein related to tubulin and FtsZ, was initially annotated as FtsZ3 or FtsZ type 2, does not affect cell division, instead, it is involved in cell shape control, required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that is essential for normal swimming motility []. CetZ co-exists with FtsZ in many archaea. These proteins contain a GTPase domain that binds and hydrolyses GTP.
Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface, including tyrosine kinases, cytokine receptors, and T-cell or B-cell receptors. There are three Cbl related proteins known to date: Cbl, CblB, and CblC/Cbl3 [
]. Cbls function as ubiquitin E3 ligase proteins, accepting ubiquitin from specific E2 ubiquitin-conjugating enzymes and transferring it to substrates, promoting their degradation [
] or endocytosis [].
This entry includes the hypothetical Rhizobium sp. protein Y4yA and similar uncharacterized bacterial proteins. These proteins are homologous to eukaryotic ornithine decarboxylase (ODC) and diaminopimelate decarboxylase (DapDC). ODC and DapDC are fold type III PLP-dependent enzymes that contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal β-sandwich domain, similar to bacterial alanine racemases. ODC participates in the formation of putrescine by catalyzing the decarboxylation of ornithine, the first step in polyamine biosynthesis. DapDC participates in the last step of lysine biosynthesis, the conversion of meso-2,6-diaminoheptanedioate to L-lysine. Proteins in this entry may function as PLP-dependent decarboxylases [
,
].
Phorbol-12-myristate-13-acetate-induced protein 1, also known as Noxa, is a p53 transcriptional target involved in the response to DNA-damaging agents [
]. Noxa can also be activated by other transcriptional factors, suggesting a broad role in the response to cellular stresses. It has been shown to promote activation of caspases and apoptosis [
,
].
