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 family clusters [
], which generally correlate with the nature of the solute bound. This entry represents the family 1. Family 1 members include:Maltose/maltodextrin-binding proteins of Enterobacteriaceae (gene malE) [
] and Streptococcus pneumoniae malXMultiple oligosaccharide binding protein of Streptococcus mutans (gene msmE)Escherichia coli glycerol-3-phosphate-binding proteinSerratia marcescens iron-binding protein (gene sfuA) and the homologous proteins (gene fbp) from Haemophilus influenzae and NeisseriaE. coli thiamine-binding protein (gene tbpA) Interestingly, these thiamin-binding proteins share protein structural similarity with thiaminase-I. They may be evolved from a common ancestor [
]. This entry also includes thiaminase-1 from Paenibacillus thiaminolyticus (Bacillus thiaminolyticus).
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 L33 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L33 has been shown to be on the surface of 50S subunit. L33 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
,
], groups:Eubacterial L33.Algal and plant chloroplast L33.Cyanelle L33.L33 is a small protein of 49 to 66 amino-acid residues.
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 [,
].This entry includes L40e and L40 from both archaea and eukaryotes. In eukaryotes, L40 is fused to ubiquitin moieties, and this fusion protein is known as UBL40 [
,
]. Specific endopeptidases cleave these precursor molecules to release ubiquitin moieties []. UBL40 plays important roles in gametogenesis [,
]. This fusion may also have a pre-cleavage function in ribosome assembly [].
Bardet-Biedl syndrome (BBS) is a rare genetic disorder belonging to the group of ciliopathies, which encompasses several diseases that are caused by defects in cilia structure and/or function, especially affecting the primary cilium. Mutations of the BBS12 gene accounts for approximately 5% of all BBS cases [
]. BBS12 is part of the BBS/CCT complex and is required or BBSome assembly []. BBSome plays a key role in mediating molecular/vesicular transport in and out of the primary cilium, and also in intraciliary trafficking as part of the intraflagellar transport machinery [].
Members of this family are heme utilization proteins, typically designated HutZ. They are members of the PPOX family (
) and, except for the lack of an N-terminal extension, are closely related to one form of heme oxidase [
]. Members typically are found in a three-gene operon with radical SAM enzyme HutW and a protein of unknown function, HutX. In Vibrio cholerae, HugZ is involved in heme degradation [
,
,
,
].
This group represents adenoviral early E1A proteins. The E1A protein is responsible for the transcriptional activation of the early genes with in the viral genome at the start of the infection process as well as some cellular genes [
].E1A disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle [
]. It also induces the disassembly of the E2F1 transcription factors from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes []. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. The stimulation of the progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication.
Members of this integral membrane protein family are found exclusively in halophilic archaea. In at least three species (Haloarcula marismortui, Haloquadratum walsbyi, and Haloferax volcanii), members are found in the gene neighbourhood of archaeosortase A, suggesting a role in protein sorting.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Proteins with this domain are small, 80 to 120 residues, and include a signal peptide, a central low-complexity region, and this roughly 31-amino acid extreme C-terminal region. Members occur paired with a variant form of exosortase. Species include Ruegeria sp., Phaeobacter gallaeciensis, Roseovarius nubinhibens ISM, and two in Methylobacter tundripaludum [
].
This C-terminal protein sorting domain has been detected in Methanohalophilus mahii DSM 5219 (five members) and Methanohalobium evestigatum Z-7303 (nine members). This domain resembles the PEP-CTERM, PEF-CTERM, and PGF-CTERM domains of other exosortase/archaeosortase systems. Member proteins co-cluster with a variant member of the exosortase/archaeosortase protein family, and represent a boutique second sorting system in these species [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this group encoded by Streptomyces coelicolor and Streptomyces avermitilis colocalize with glycogen metabolism cluster I proteins (such as glycogen phosphorylase). However, proteins from other organisms are found in different genomic contexts.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Membrane-derived oligosaccharides (MDO) are members of a family of glucans found in the periplasmic space of Gram-negative bacteria. MdoG has been shown to be necessary for the synthesis of MDO [
], but its exact function is notknown yet. MdoD, an MdoG paralog, is a twin-arginine-dependent periplasmic protein that controls osmoregulated periplasmic glucan backbone structures [
]; see also [].
Membrane-derived oligosaccharides (MDO) are members of a family of glucans found in the periplasmic space of Gram-negative bacteria. MdoG has been shown to be necessary for the synthesis of MDO [
], but its exact function is not known yet. This entry contains proteins that are involved in the biosynthesis of osmoregulated periplasmic glucans (OPGs). They belong to the opgD/opgG family.
This entry represents a protein region that is cleaved from a bunyavirus polyprotein to become the nonstructural protein NSm (encoded by the M segment). This region is flanked by glycoprotein Gn (also known as GP2) and glycoprotein Gc (also known as GP1), which plays a role in virion budding at Golgi tubes and in the subcellular location of Gc protein [
].
Chlamydiae/Verrucomicrobia/Planctomycetes small basic protein
Type:
Family
Description:
Members of this protein family are commonly found next to markers of rRNA processing such as YbeY. They are extremely lineage-restricted, in the Planctomycetes and Chlamydiae/Verrucomicrobia group. Since classification is based on rRNA molecular phylogeny, this provides additional support for a role in rRNA metabolism. This small protein, about 50 amino acids in length, is rich in basic residues, a third line of support for rRNA interaction.
Thin aggressive fibres known as curli fibres or fimbriae (curli; Tafi) are cell-surface protein polymers found in Salmonella typhimurium and Escherichia coli that mediate interactions important for host and environmental persistence, development of biofilms, motility, colonisation and invasion of cells, and conjugation [
]. Four general assembly pathways for different fimbriae have been proposed, one of which is extracellular nucleation-precipitation (ENP), which differs from the others in that fibre-growth occurs extracellularly. Thin aggregative fimbriae are the only fimbriae dependent on the ENP pathway. Tafi were first identified in Salmonella spp and the controlling operon termed agf; however subsequent isolation of the homologous operon in E coli led to its being called csg. Tafi are known as curli because, in the absence of extracellular polysaccharides, their morphology appears curled; however, when expressed with such polysaccharides their morphology appears as a tangled amorphous matrix. The gene agfC is found to be transcribed at low levels, localised to the periplasm in a mature form, and in combination with AgfE is important for AgfA extracellular assembly, which facilitates the synthesis of Tafi. The genes involved in Tafi production are organised into two adjacent divergently transcribed operons, agfBAC and agfDEFG, both of which are required for biosynthesis and assembly [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Many bacterial pathogens deliver effector proteins into host cells via a type III secretion system. These effector proteins then alter the host cell's biology in ways that are advantageous to the pathogen. The NleG protein and its homologues form the largest family of effector proteins in the enterohemorrhagic Escherichia coli O157:H7, with 14 members identified in the Sakai strain alone [
]. NleG family members share a conserved C-terminal domain that forms a structure similar to the RING finger/U-box domain found in eukaryotic ubiquitin ligases []. They selectively interact with human E2 ubiquitin conjugating enzymes and exhibit in vitro activity typical of eukaryotic E3 ligases, though the role of this activity in pathogenesis is not yet known.
This entry represents a variant form of the PEP-CTERM C-terminal protein-sorting domain, with a consensus motif IPTL replacing the more typical VPEP. A majority of these sequences have a WG (Trp-Gly) motif at positions 7-8 of the domain. Species with multiple (up to 15) copies of this domain include Acidovorax citrulli, Acidovorax delafieldii 2AN, Delftia acidovorans SPH-1, and gamma proteobacterium NOR5-3 [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Proteins closely related to MJ_1469.1 from Methanocaldococcus jannaschii DSM 2661 are designated archaeosortase D (ArtD). ArtD appears to be a dedicated protein-sorting enzyme with a single target, a PKD domain
repeat protein encoded by adjacent gene. This model describes the C-terminal putative protein-sorting region structurally similar to PEP-CTERM and found only on these methanogen PKD domain proteins [
].
This entry represents a sporadically distributed conserved hypothetical protein in which complete members average over 500 amino acids in length, although matching sequences frequently are truncated or broken into tandem ORFs. Regular co-clustering with known markers of mobility (integrases, transposases, phage proteins, restriction enzymes, etc.) suggests this family also is part of the mobilome. The function is unknown.
This protein family is related to the predicted protein-sorting transpeptidase Exosortase (EpsH), with the Cys, Arg, and His putative active site residues preserved, but it is strictly archaeal and is not associated with any known PEP-CTERM-like target sequence. The immediate gene neighbourhood in most genomes suggests RNA (methylase, cyclase) and cofactor (thiamine pyrophosphate) metabolism. The function is unknown. It is designated archaeosortase family protein ArtE [
].
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 L38e forms part of the 60S ribosomal subunit [
].
DNA-repair protein Xrcc1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with beta-Pol, ligase III and PARP [
]. The NMR solution structure of the Xrcc1 N-terminal domain (Xrcc1 NTD) shows that the structural core is a β-sandwich with β-strands connected by loops, three helices and two short two-stranded β-sheets at each connection side. The Xrcc1 NTD specifically binds single-strand break DNA (gapped and nicked) and a gapped DNA-beta-Pol complex [].
This Domain of unknown function 61 (DUF61) family of proteins are widely distributed in archaea. In crenarchaea, the genes of DUF61 proteins are in an operon containing two genes of box C/D RNA protein complexes. The NMR structure of a DUF61 family member from the hyperthermophilic archaeon Sulfolobus solfataricus revealed a rigid core structure and flexible N- and C-terminal regions, including a negatively-charged independent C-terminal helix. The core structure consists of N- and C-terminal subdomains, in which the C-terminal subdomain shows significant structural similarity with several nucleic acid binding proteins [
].
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. CbiM is the substrate-specific component of the complex and is a seven-transmembrane protein []. This entry also includes related proteins, such as NikMN, which may be involved in nickel transport []. The CbiMNQO and NikMNQO systems form part of the coenzyme B12 biosynthesis pathway [].
CRISPR-associated protein Cas1, cyanobacteria-type
Type:
Family
Description:
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 describes a type of Cas1 proteins found mainly in cyanobacteria.
This entry represents a family of archaeal proteins, including UPF0201 protein PH1010 from Pyrococcus horikoshii (
), which is composed of five α-helices (1-5) and eight β-strands (1-8) with the following topology: β-1, α-1, β-2, β-3, α-2, α-3, β-4, β-5, α-4, β-6, α-5, β-7, β-8. The first six β-strands (1-6) form a slightly twisted antiparallel β-sheet and face five α-helices on one side. The last two β-strands form an antiparallel β-sheet in the C terminus. PH1010 forms a characteristic homodimer structure in the crystal. Dimerisation of the molecule is crucial for function. The structure resembles that of some ribosomal proteins such as the 50S ribosomal protein L5 [
]. Although the structure resembles that of the RRM-type RNA-binding domain of the ribosomal L5 protein, the residues involved in RNA-binding in the L5 protein are not conserved in this family []. Despite this, RNA-binding protein PAB1135 from Pyrococcus abyssi (), which belongs to this family, bind to double-stranded RNA in a non-sequence specific manner [
].
Sp17 was originally proposed to be a sperm-specific protein that plays a role in sperm-egg interactions by binding to the zona pellucida via two conserved heparin-binding motifs [
]. Later, it was found expressed in other tissues and may have a regulatory role in an A-kinase anchoring protein complex [,
].
HypD is involved in the hyp operon which is needed for the activity of the three hydrogenase isoenzymes in Escherichia coli. HypD is one of the genes needed for formation of these enzymes [
]. This protein has been found in Gram-negative and Gram-positive bacteria and Archaea. HypD contains many possible metal binding residues, which may bind to nickel. Transposon insertions into HypD resulted in Rhizobium leguminosarum mutants that lacked any hydrogenase activity in symbiosis with peas [
].
This entry describes archaeal proteins of unknown function. This family of orthologues is restricted to, but universal among, the completed archaeal genomes so far. Eubacterial proteins showing at least local homology include slr1870 from Synechocystis sp. (strain PCC 6803) and two proteins from Aquifex aeolicus, none of which is characterised.
RepA is a hexameric replicative helicase encoded by a plasmid, which is found in bacteria. RepA is a 5'-3' DNA helicase which can utilize ATP, GTP and CTP to a lesser extent [
,
].
Pericentriolar material 1 protein is required for centrosome assembly and function. It is essential for the correct localisation of several centrosomal proteins and required to anchor microtubules to the centrosome [
]. It is probably involved in the biogenesis of cilia [].
Hepatitis B X-interacting protein (HBXIP, also known as LAMTOR5) was originally recognised for its association with the X protein of hepatitis B virus (HBV) and ability to down-regulate HBV replication [
]. When complexed to the anti-apoptotic protein survivin, HBXIP interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerised APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway []. HBXIP is one of the Ragulator components that are required for mTORC1 activation by amino acids []. It is also part of the AA (amino acid) sensing machinery in human CD4+ T cells [].
High potential iron-sulphur proteins (HiPIP) [
,
] are a specific class of high-redox potential 4Fe-4S ferredoxins that functions in anaerobic electron transport and which occurs commonly in purple photosynthetic bacteria and in other bacteria, such as Paracoccus denitrificans and Thiobacillus ferrooxidans [].HiPIPs seem to react by oxidation of [4Fe-4S]2+ to [4Fe-4S]3+The HiPIPs are small proteins which show significant variation in their sequences, their sizes (from 63 to 85 amino acids), and in their oxidation- reduction potentials. As shown in the following schematic representation the iron-sulphur cluster is bound by four conserved cysteine residues.[4Fe-4S cluster]
| | | |xxxxxxxxxxxxxxxxxxxCxCxxxxxxxCxxxxxCxxxx
'C': conserved cysteine involved in the binding of the iron-sulphur cluster.
This entry represents the inner membrane protein YejM, which is predicted to be membrane sulphatase, as well as uncharacterised proteins with similar sequence.
Dictyostelium is usually a unicellular soil organism. However, depletion of food triggers chemotactic aggregation resulting in the formation of a multicellular organism. SmlA is required for the proper function of a cell-counting mechanism that regulates organism size in Dictyostelium. SmlA affects secretion of the counting factor complex, whose concentration is indirectly proportional to aggregate size [
,
].
This family comprises eukaryotic and prokaryotic proteins. It includes mammalian IQ domain-containing protein H, also known as NYD-SP5, which has a potential role in testis development and spermatogenesis [
].
NF-kappa-B inhibitor-like protein 1 (NFKBIL1, also known as IKBL) is a member of the nuclear IkB family. Classical IkB proteins retain NF-kB dimers in the cytoplasm; IkBL belongs to the atypical or nuclear IkB proteins [
]. It inhibits LPS-induced NF-kB activation and transcription of TNF-alpha and IL-6 [].
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres [
]. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].
Members of this protein family are homologous to SecA and part of the accessory Sec system. This system, including both five core proteins for export and a variable number of proteins for glycosylation, operates in certain Gram-positive pathogens for the maturation and delivery of serine-rich glycoproteins such as the cell surface glycoprotein GspB in Streptococcus gordonii [
,
].
This family includes CFAP97D1 (CFAP97 domain-containing protein 1) and CFAP97D2. CFAP97D1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice [
].
This entry consists of AGP19 from Arabidopsis and related proteins. AGP19 is a member of the lysine-rich arabinogalactan protein (AGP) subfamily within the hydroxyproline-rich glycoprotein (HRGP) superfamily. AGPs are hyperglycosylated proteins implicated in different aspects of plant growth and development. Protein backbones of AGPs are rich in Pro/Hyp (hydroxyproline), Ser, Ala and Thr and are modified by the addition of type II arabinogalactan polysaccharides and arabinose oligosaccharides to Hyp residues [
]. AGP19, as the other lysine-rich members AGP17 and AGP18, contains a C-terminal lysine-rich region and is thought to be related to sexual reproduction in flowering plants [,
].
This group contains RocB of Bacillus subtilis and related proteins. RocB is one of the three genes found in the rocABC operon in B. subtilis, which is sigma L dependent and induced by arginine, suggesting it is involved in the arginine degradation pathway. The function of members of this family is unknown, though they are related to metallopeptidases belonging to MEROPS peptidase family M20, subfamily M20A (clan MH).
The function of coiled-coil domain-containing protein 138 is not clear. However, it has been localised to basal bodies, suggesting to play a role in centrosomal and ciliary biology [
].
This entry represents ribosomal protein L19e from eukaryotes. L19e is found in the large ribosomal subunit of eukaryotes and archaea. L19e is distinct from the ribosomal subunit L19, which is found in prokaryotes. It consists of two small globular domains connected by an extended segment. It is located toward the surface of the large subunit, with one exposed end involved in forming the intersubunit bridge with the small subunit. The other exposed end is involved in forming the translocon binding site, along with L22, L23, L24, L29, and L31e subunits [
].
This entry represents the ribosomal protein L19e from archaea. L19e is found in the large ribosomal subunit of eukaryotes and archaea. L19e is distinct from the ribosomal subunit L19, which is found in prokaryotes. It consists of two small globular domains connected by an extended segment. It is located toward the surface of the large subunit, with one exposed end involved in forming the intersubunit bridge with the small subunit. The other exposed end is involved in forming the translocon binding site, along with L22, L23, L24, L29, and L31e subunits [
].
This family is conserved in yeast and apicomplexa. The representative, SPBC365.16, is an uncharacterized mitochondrial membrane protein from fission yeast.
p38 kinases are mitogen-activated protein kinases (MAPKs), which serve as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines [
].Vertebrates contain four p38 kinases, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns.p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine [
]. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest []. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main kinase involved in regulating the differentiation and apoptosis of keratinocytes [].
p38 kinases are mitogen-activated protein kinases (MAPKs), which serve as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines [
].Vertebrates contain four p38 kinases, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns.p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles [
,
]. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription []. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression []. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes [].
p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines [
]. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease [,
].Vertebrates contain four p38 kinases, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns.p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis [
]. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway []. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf [].
This entry represents the upper collar protein (also known as portal protein Gp10) superfamily from various bacteriophage. The upper collar protein of Bacteriophage phi-29 is composed of twelve 36kDa subunits with 12-fold symmetry. It consists of two domains: an α-helical bundle domain and a β-barrel domain. This protein is located between the head and the tail of the bacteriophage and acts as the central component of a rotary motor that packages the genomic dsDNA into pre-formed proheads. This motor consists of the upper collar protein, surrounded by a 29-encoded, 174-base, RNA and a viral ATPase protein [
,
].
H(2)-forming methylenetetrahydromethanopterin dehydrogenase-related protein
Type:
Family
Description:
This family consists of two members, designated HmdII and HmdIII, restricted to methanogens. They are homologues of the enzyme Hmd, a H2-forming N(5),N(10)-methenyltetrahydromethanopterin dehydrogenase. Because all three isozyme forms are present in each of the corresponding sequenced genomes, it has been suggested that HmdII and HmdIII may not exhibit Hmd activity and may have a different biological function [
]. Based on its ability to bind to aminoacyl-tRNA synthetases and tRNA, a role for HmdII has been proposed as a regulator of protein synthesis that senses intracellular methylene-H4 MPT concentration [].
Members of this protein family are DltB, part of a four-gene operon for D-alanyl-lipoteichoic acid biosynthesis that is present in the vast majority of low-GC Gram-positive organisms [
]. It is an O-acyltransferase that catalyzes D-alanylation of both teichoic acid and lipoteichoic acid (LTA) []. D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall [].
Proteins in this entry include the Immunity protein YezG from Bacillus subtilis and Type VII secretion system protein EsaG from Staphylococcus aureus. YezG is the antitoxin component of a LXG toxin-antitoxin (TA) module that promote kin selection, mediate competition in biofilms, and drive spatial segregation of different strains, probably helping to avoid warfare between strains in biofilms [
]. EsaG is part of toxin-antitoxin system that counteracts the toxic effect of EssD via direct interaction [].YezG has an α/β structure with an antiparallel β-sheet.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This family consists of various adenovirus penton base
proteins (also known as Protein III) [], from both the mastadenoviridae having mammalian hosts and the aviadenoviridae having avian hosts. The penton base is a major structural protein forming part of the penton which consistsof a base and a fibre, the pentons hold a morphologically prominent
position at the vertex capsomer in the adenovirus particle []. In mammalian adenovirus there is only one tail on each base where as
in avian adenovirus there are two [].The penton base proteins are also Involved in virus secondary attachment to host cell after initial attachment by the fibre protein [
].
This family consist of the C proteins (C', C, Y1, Y2) found in the Paramyxovirinae, e.g. Human parainfluenza virus 3, and Sendai virus. The C proteins effect viral RNA synthesis having both a positive and negative effect during the course of infection [
].The paramyxovirinae have a negative-strand ssRNA genome of 15.3 kb from which six mRNAs are transcribed, five of these are monocistronic.
The P/C mRNA is polycistronic and has two overlapping open reading frames P and C, C encodes the nested C proteins C', C, Y1 and Y2 [].
Matrix (M) protein is an important structural component of rhabdovirus virions, and also plays a number of roles during the replication cycle of the virus [
]. It is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions [].
C. elegans Unc-13 is a phorbol ester/diacylglycerol-binding protein that plays a role in vesicle maturation during exocytosis [
,
]. Unc-13 disruption causes diverse defects in the nervous system [,
]. Mammals contain three Unc-13 homologues: Unc-13 A, B and C (also known as Munc13-1/2/3) []. Unc13 homologue C is cerebellum-specific and regulates cerebellar synaptic transmission []. Homologues A and B are involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion []. They are essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses [].Unc-13 and its homologues contain both C1 and C2 domains. There are at least two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. The central C2 domain (C2B) is part of a C1-C2 tandem that functions in part to inhibit calcium-triggered neurotransmitter release. The C1 domain of Munc13 binds diacylglycerol (DAG) and beta phorbol esters (beta-PEs), while the neighbouring C2 domain (C2B) binds calcium and anionic phospholipids with a preference for both PI(4)P and PI(4,5)P2 [
]. This entry represents the second C2 domain, C2B, and has a type-II topology.C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements, type I and type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions [,
,
,
,
,
,
,
].
In Gram-negative bacteria the biogenesis of fimbriae (or pili) requires a two-
component assembly and transport system which is composed of a periplasmicchaperone and an outer membrane protein which has been
termed a molecular 'usher' [,
,
]. The usher protein is rather large (from 86 to
100kDa) and seems to be mainly composed of membrane-spanning β-sheets, astructure reminiscent of porins.
Although the degree of sequence similarity of these proteins is not very high,they share a number of characteristics. One of these is the presence of two pairs
of cysteines, the first one located in the N-terminal part and the secondat the C-terminal extremity that are probably involved in disulphide bonds.
The best conserved region is located in the central part of these proteins [,
].
This entry represents the Csn2 superfamily of Cas proteins, which are found only in CRISPR-containing species, near other CRISPR-associated proteins (cas), as part of the NMENI subtype of CRISPR/Cas loci. The species range so far for this subtype is animal pathogens and commensals only. This protein is present in some but not all NMENI CRISPR/Cas loci [
].The structure of Csn2 contains two domains: an alpha/beta domain and an α-helical domain with significant hinge motion between these two domains [
]. Sn2 is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca(2+) ions [].
Testis-expressed sequence 15 protein (TEXT15), also known as cancer/testis antigen 42, is a testis-specific protein. It is also expressed in several cancers [
,
]. TEXT15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis [].
Centrosomal protein of 95kDa is localised to the centrosome and the spindle pole [
]. Its function is not clear. It is phosphorylated upon DNA damage, probably by ATM or ATR [,
].
Microtubule-associated protein 10 (MAP10, also known as MTR120/KIAA1383) localises to stabilised MTs during interphase and to the mitotic apparatus during mitosis. It may promote microtubule stability and ensures normal progress of cytokinesis [
].This entry represents a C-terminal domain found in microtubule-associated protein 10.
Members of this protein family show distant local sequence similarity to a number of S-adenosyl-methionine-dependent methyltransferases. The family is identified by Partial Phylogenetic Profiling as closely tied to the DNA phosphorothioation system (dnd), and members are found adjacent to dnd genes in at least 13 species (Streptomyces lividans TK24, Shewanella frigidimarina NCIMB 400, Mycobacterium abscessus ATCC 19977, Nostoc punctiforme PCC 73102, Vibrio fischeri MJ11, etc.). The DNA phosphorothioation enables a novel form of restriction enzyme activity. Most members of this family appear in species with the DNA phosphorothioation system.
Ribosomal protein L19 is one of the proteins from the large ribosomal subunit [
,
]. In Escherichia coli, L19 is known to be located at the 30S-50S ribosomal subunit interface [] and may play a role in the structure and function of the aminoacyl-tRNA binding site. It belongs to a family of ribosomal proteins, including L19 from bacteria and the chloroplasts of red algae.
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 [
,
].This entry represents the ribosomal protein L27 found in fungi, plants, algae and vertebrates
[,
].
Members of this Actinobacterial protein family contain the signal peptide domain
, for the variant SipW form of the signal peptidase I family. The remainder of this protein, however, differs from families such as Peptidase_M73 (
) and YqxM (
) that share the same signal peptide domain. The two known targets for export by the SipW signal peptidase in Bacillus subtilis act in producing biofilm matrix material, but the function for this Actinobacterial family is not known.
Members of this largely Clostridial protein family contain the signal peptide
for the variant SipW form of the signal peptidase I family. The remainder of this protein, however, differs from families such as Peptidase_M73 (
) and YqxM (
) that share the same signal peptide domain. The two known targets for export by the SipW signal peptidase in Bacillus subtilis act in producing biofilm matrix material, but the function for the proteins in this entry is not known.
There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. The structure of the Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum) protein has been determined but no evidence of the function is available yet.
